Background The ability of allogeneic bone marrow transplantationto cure chronic myeloid leukemia (CML) is due to both the conditioningregimen and the antileukemic effects of the lymphocytes in thegrafted marrow. We studied the ability of interferon alfa-2band infusions of mononuclear cells from the marrow donor toinduce a graft-versus-leukemia reaction in patients with CMLin relapse after bone marrow transplantation.
Methods Eleven patients with relapsed CML after allogeneic bonemarrow transplantation were treated with interferon alfa-2band infusions of mononuclear cells. The patients were monitoredfor toxic effects, for hematologic and cytogenetic responses,and, with use of the polymerase chain reaction, for eliminationof cells containing the bcr/abl messenger RNA transcript characteristicof the leukemic cells.
Results Six of the eight patients with stable CML after relapsehad complete remissions according to molecular genetic criteria,since no cells with bcr/abl messenger RNA transcripts were detected(the method can identify 1 leukemic cell among 1 million normalcells). The three patients with accelerated CML after relapsedid not enter remission. Myelosuppression was prominent in eightpatients. Grade I acute graft-versus-host disease (GVHD) occurredin six patients, and grade III acute GVHD occurred in three.Limited chronic GVHD developed in five patients.
Conclusions The induction of a graft-versus-leukemia reactionwith interferon alfa-2b and infusions of donor mononuclear cellsin patients with CML in relapse after bone marrow transplantationis an effective antileukemic therapy that may offer an alternativeto a second marrow transplantation.
Allogeneic bone marrow transplantation cures over 50 percentof patients with chronic myeloid leukemia (CML) when performedduring the chronic phase of the disease1,2. This response isrelated to both the conditioning regimen and the graft-versus-leukemiaeffect (the immune potential of the donor graft to react againstthe patient's leukemic cells). The success of allogeneic transplantationis limited in part by graft-versus-host disease (GVHD) and bythe relapse of CML. Relapses can be cured with a second transplantation,but with increased regimen-related morbidity and poor survivalrates3. A safer, more effective approach is clearly desirable.One such approach is the induction of a graft-versus-leukemiareaction without a second transplantation.
Graft-versus-leukemia effects have been demonstrated in animalmodels of transplantation,4,5 but evidence of their importancein clinical transplantation is indirect. For instance, the developmentof GVHD after transplantation is associated with protectionagainst relapse2,6,7. In addition, in patients with CML, bonemarrow grafts depleted of T cells result in a low incidenceof GVHD but a relapse rate of 30 to 50 percent, as comparedwith a rate of 10 to 20 percent for unmodified bone marrow grafts1,2,6,8.
A graft-versus-leukemia reaction has been induced in patientswith recurrent CML after bone marrow transplantation. Kolb etal. induced cytogenetic remissions in three patients with relapsedCML by administering interferon-alfa and mononuclear cells obtainedfrom the original marrow donor9. Cytogenetic analysis is usefulwhen approximately 1 in 30 cells contains the characteristicchromosomal translocation of CML (the Philadelphia chromosome[Ph1]). In this translocation, the abl proto-oncogene is translocatedfrom chromosome 9 to chromosome 22 adjacent to the bcr gene.The polymerase chain reaction (PCR) is a far more sensitivemethod of detecting this translocation than is cytogenetic analysis;by amplifying transcripts of the chimeric bcr/abl gene, a singleleukemic cell among 1 million normal cells can be identified10.Importantly, the detection of bcr/abl transcripts after transplantationcorrelates with an increased risk of relapse10. In case reportsfrom other groups, the antileukemic effect of mononuclear-cellinfusions was confirmed in three patients by PCR11,12. On thebasis of these studies, we administered interferon alfa-2b anddonor mononuclear cells to 11 patients with recurrent CML toinduce a graft-versus-leukemia reaction, using serial testsfor the bcr/abl transcripts to monitor the patients.
Methods
Patients' Characteristics
We studied 11 consecutive patients with CML in relapse afterallogeneic bone marrow transplantation. All patients had a hematologicrelapse requiring cytoreductive therapy. No patient requiredimmunosuppression for chronic GVHD, and all the patients hadan Eastern Cooperative Oncology Group performance status of0 (a score of 0 indicates no symptoms, and a score of 4 severedisability). The study was approved by the Human Research Committeeof Brigham and Women's Hospital, and written informed consentwas obtained from all patients and donors.
The characteristics of the patients are shown in Table 1. Allhad undergone allogeneic transplantation of bone marrow obtainedfrom an HLA-identical sibling for chronic CML. For prophylaxisagainst GVHD at the time of transplantation, nine patients receivedmarrow grafts depleted of T cells13,14,15 and two patients receivedcyclosporine and methotrexate16. The median length of time fromtransplantation to relapse was 13 months (range, 6 to 44), andthe median time from relapse to the first infusion of mononuclearcells was 22 months (range, 10 to 56) (Table 1). The grade ofGVHD after initial transplantation is shown in Table 2.
Table 2. Extent of Acute and Chronic GVHD in 11 Patients with CML after Treatment with Interferon Alfa-2b and Mononuclear-Cell Infusions.
CML was classified as being in a stable phase, an acceleratedphase, or a blast crisis according to the criteria of the InternationalBone Marrow Transplant Registry,17 except that the disease inpatients with complex chromosomal abnormalities was not classifiedas being in an accelerated phase unless other criteria werealso met. Eight patients had stable CML, and three had acceleratedCML. One patient (Patient 11) with accelerated CML had a blastcrisis during therapy and withdrew from the study after twoinfusions of mononuclear cells to receive chemotherapy.
Interferon Therapy
The treatment protocol is shown in Figure 1. The patients weretaught to inject themselves with interferon alfa-2b (IntronA, Schering-Plough, Kenilworth, N.J.). The projected daily dosewas 5 million units per square meter of body-surface area subcutaneously,although treatment was usually started at a lower dose and titratedaccording to the patient's tolerance and hematologic response.Reasons for reductions in the dose included the occurrence ofsevere influenza-like symptoms, depression, and a white-cellcount below 4000 per cubic millimeter or a platelet count below100,000 per cubic millimeter. Interferon alfa-2b alone controlledperipheral-blood counts in 10 patients; 1 patient required hydroxyureain addition to interferon alfa-2b. Patients received interferonalfa-2b for 6 to 12 weeks before the first infusion of cells.Treatment with interferon alfa-2b was continued throughout theinfusions and for four weeks after the final infusion.
Nine patients received four weekly infusions of mononuclearcells freshly obtained from the original bone marrow donor byleukapheresis (Figure 1). One patient (Patient 8) received onlyone infusion because of venous-access difficulties in the donor,and one patient (Patient 11) withdrew from the study, as notedabove. The leukapheresis was carried out with a Cobe Spectraapheresis system (Cobe Laboratories, Lakewood, Colo.); the totaldose of cells infused per patient is shown in Table 1.
Evaluation of Patient Response
The patients were evaluated at least weekly for evidence ofGVHD, complete blood counts and differential counts were obtained,and serum electrolyte and liver-enzyme concentrations were measured.Bone marrow was obtained from most patients two weeks beforethe first infusion and two to eight weeks after the final infusionfor evaluation of responses according to morphologic, cytogenetic,and molecular genetic criteria.
Acute GVHD was graded on a four-point scale (on which I indicatesmild disease, and IV severe disease), and chronic GVHD was classifiedas limited or extensive, as previously described18,19. Skinor liver biopsies were performed when indicated for confirmationof GVHD. All patients with acute GVHD were initially treatedwith oral prednisone (1 to 3 mg per kilogram of body weightper day), with additional therapy given at the discretion ofthe investigators.
Definition of Remission and Statistical Analysis
The results are presented as of June 30, 1993. Hematologic remissionwas defined as the return of normal blood counts and bone marrowcellularity in the absence of antileukemic therapy. Severalpatients with mild, stable anemia or thrombocytopenia were consideredto be in hematologic remission. Cytogenetic remission was consideredto be present when all bone marrow metaphases were normal. (Cytogeneticanalysis was performed by the cytogenetics laboratory at theDana-Farber Cancer Institute, Boston.) Molecular genetic remissionwas defined as the inability to detect bcr/abl messenger RNA(mRNA) transcripts by PCR, as described below. The cumulativeprobability of entering molecular genetic remission was calculatedaccording to the method of Kaplan and Meier,20 and the relationbetween the amount of cells infused and remission was evaluatedwith Student's t-test.
Molecular Genetic Analysis
Analysis of bcr/abl Transcripts
Peripheral-blood granulocytes, mononuclear cells, or bone marrowcells were obtained at various times after the infusion of mononuclearcells, and RNA was prepared as previously described10. RNA PCRwas performed with an abl-sequence-specific reverse transcriptaseprimer followed by PCR amplification with abl- and bcr-specificprimers10. Second-round PCR (35 cycles per round) with nestedinternal bcr and abl primers was performed on all samples, andamplification of the bcr/abl transcript was detected by visualizationon ethidium bromide-stained agarose gels. Studies have shownthat this method can detect 1 leukemic cell per 1 million normalcells10. The presence of intact RNA and the adequacy of thesynthesis of complementary DNA were evaluated by single-roundPCR with abl-sequence-specific PCR primers10. Mock RNA preparationswere run as negative controls.
Analysis of Engraftment by PCR
Blood from Patients 2 and 3 was obtained before the mononuclear-cellinfusions, and cells were separated by Ficoll-Hypaque centrifugationinto layers of mononuclear cells and granulocytes. Aliquotsof DNA (10 microl) prepared from both cell fractions were usedfor amplification by PCR and engraftment analysis21,22. PatientDNA and donor DNA were screened for distinguishing polymorphismswith a series of PCR primers flanking known polymorphic regions22.Primers for the parathyroid hormone (PTH) gene23 identifieda polymorphism in the host DNA but not in donor DNA (Figure 2).After therapy, blood or bone marrow samples were obtainedat various times. The DNA was amplified with PTH-specific primers,and the products were analyzed22. The host-specific allele wasquantitated by hybridization with an oligonucleotide specificfor the recipient allele, the probe was removed, and the samplewas rehybridized with an internal oligonucleotide consistingof an invariable PTH sequence.
Figure 2. Progressive Disappearance of Recipient's Cells after Infusions of Donor Mononuclear Cells.
Samples of the recipient's DNA were analyzed by PCR amplification of a polymorphic segment of the PTH gene followed by slot blotting. The results of hybridization with the host-allelle-specific (Taq1-negative) oligonucleotide probe are shown in the upper row. The probe was then removed, and the samples were rehybridized with an invariable allele-specific oligonucleotide probe (lower row). The plus-minus sample in the first slot represents the PCR product derived from a person known to be heterozygous for the Taq1 polymorphism. Gran denotes granulocytes, MNC mononuclear cells, and BC buffy coat.
Results
Response to Interferon Alfa-2b
Hematologic control of CML was achieved with interferon alfa-2bin 10 of the 11 patients. However, no patient had a cytogeneticor molecular genetic remission before the infusion of donormononuclear cells. After 4 to 10 weeks of therapy with interferonalfa-2b, marrow biopsies showed hypercellularity (cellularity,80 to >95 percent), with 74 to 100 percent of metaphasescontaining the Ph1 chromosome in all nine patients from whomwe could aspirate marrow (eight patients had other complex karyotypicabnormalities). In the other two patients, cytogenetic studiesof peripheral blood revealed Ph1-positive cells. We detectedbcr/abl mRNA transcripts in the marrow or blood of all ninepatients evaluated.
Hematologic Response to Interferon Alfa-2b and Mononuclear-Cell Infusions
The eight patients with stable CML had complete hematologicresponses. After interferon alfa-2b was discontinued, the bloodcounts remained stable in these patients without the need forfurther treatment with interferon alfa-2b, hydroxyurea, or othertypes of cytoreductive therapy. Five patients had transientabsolute granulocyte counts below 500 per cubic millimeter.In the patients who responded, the decline in peripheral-bloodcounts coincided with the development of clinically evidentacute GVHD (Figure 3). A bone marrow evaluation two to eightweeks after the final infusion in six patients who respondedshowed a decrease in cellularity to 5 to 30 percent. One patient(Patient 5) died of aspergillus infection after grade III acuteGVHD and profound pancytopenia developed. Bone marrow aplasiadeveloped in a second patient (Patient 3). Quantitative analysisof peripheral blood from this patient immediately before thefirst infusion of mononuclear cells demonstrated residual productionof donor granulocytes and mononuclear cells (Figure 2). Althoughmore than 99 percent of hematopoiesis was of donor origin byday 115 (Figure 2), the patient's bone marrow remained hypocellular(95 percent fat), and she was dependent on platelet and red-celltransfusions. Hematopoietic recovery did not occur until donorbone marrow was administered on day 181; she was in completeremission after 558 days of follow-up (Figure 3).
Figure 3. White-Cell Response in Two Patients with CML in Relapse after Infusions of Donor Mononuclear Cells.
Open circles indicate positive tests for bcr/abl mRNA transcripts, and solid circles negative tests. The onset of acute GVHD was associated with a decline in the white-cell count and a loss of bcr/abl mRNA transcripts. Leukopenia persisted in Patient 3 until bone marrow was infused on day 181.
Cytogenetic and Molecular Genetic Responses
Six of the eight patients who had a hematologic response hada complete cytogenetic remission according to blood and bonemarrow analyses and a complete molecular genetic remission asdocumented by the absence of detectable bcr/abl mRNA transcripts.The actuarial probability of entering a complete molecular geneticremission was 69 percent after a median follow-up of 355 days(range, 50 to 709) (Figure 4). The median length of time untilbcr/abl transcripts were undetectable was 57 days (range, 42to 116) after the first infusion of mononuclear cells. Noneof these six patients had a molecular genetic or cytogeneticrelapse during a median follow-up of 461 days (range, 260 to709). Hematopoiesis was confirmed to be of donor origin by sex-chromosomeanalysis, blood-type analysis, or the demonstration of the lossof a marker chromosome. In addition, PCR analysis of engraftmentin Patient 2 (data not shown) and Patient 3 (Figure 2) demonstratedthat more than 99 percent of hematopoiesis was of donor originat the time of complete remission.
Figure 4. Actuarial Probability of Entering Molecular Genetic Remission.
Open diamonds indicate patients who were persistently positive for bcr/abl mRNA transcripts during follow-up, and solid diamonds patients in complete molecular genetic remission during follow-up. Each asterisk denotes a patient who died. Two patients (Patients 4 and 11) had clinical CML with Ph1-positive metaphases in the marrow, and PCR for bcr/abl mRNA transcripts was not performed.
The three patients with accelerated CML did not enter remission.However, Patient 7 improved, and her blood counts stabilizedduring treatment with a lower dose of interferon alfa-2b. Patient11 withdrew from the study after two infusions to receive chemotherapybecause of progression to blast crisis. Grade I acute GVHD developedin Patient 4, but she had no hematologic response and died ofcomplications of blast crisis and sepsis 50 days after the firstinfusion.
Toxicity
Acute GVHD
Acute GVHD developed in nine patients a median of 32 days (range,22 to 87) after the first infusion (Table 2). The number ofinfusions was not reduced in any patient as a result of acuteGVHD, although grade I acute GVHD developed after only a singleinfusion in one patient who responded (Patient 8) (additionalinfusions could not be given because of venous-access difficultiesin the donor). Six patients had grade I acute GVHD, and threepatients grade III. All were initially treated with corticosteroids;three patients required additional treatment with cyclosporine,and one patient required additional treatment with azathioprine.One patient (Patient 6) with grade III acute GVHD also receivedantithymocyte globulin and interleukin-1-receptor antagonist,24with complete resolution of the disease. All patients with acytogenetic or molecular genetic response had GVHD. There wasno correlation between the cell dose and either the responseor the severity of GVHD.
Chronic GVHD
Limited chronic GVHD developed in five of the eight patientswho were followed for more than 100 days (Table 2). ChronicGVHD was manifested by a recurrent skin rash in one patient,oral mucositis in two patients, biopsy-proved chronic GVHD ofthe liver25 in two patients, and synovitis in one patient. ChronicGVHD was controlled with immunosuppressive therapy in all fivepatients.
Opportunistic Infections
Life-threatening opportunistic infections developed in threepatients during treatment for GVHD. One patient had granulocytopeniaand died of aspergillus sepsis. The second patient had a facialabscess due to Staphylococcus aureus and aspergillus infectionof the lung and liver, and the third patient had Pneumocystiscarinii pneumonia and aspergillus infection of the lung andbrain.
Discussion
Allogeneic bone marrow transplantation transfers both hematopoieticstem cells and alloreactive donor lymphocytes, which producea form of adoptive immunotherapy. The antitumor effect mediatedby immunocompetent donor cells is known as the graft-versus-leukemiaeffect and has been well characterized in murine models of transplantation4,5.In humans, the presence of the graft-versus-leukemia reactionhas been supported by indirect evidence that relapse rates aresignificantly higher after T-cell depletion of donor bone marrow2,6,7or syngeneic transplantation6. The development of GVHD aftertransplantation is associated with lower relapse rates,2,6,7and patients with a relapse of leukemia may enter remissionwhen GVHD follows the withdrawal of immunosuppression26.
The responses in this trial provide evidence of a graft-versus-leukemiareaction in humans with CML in relapse after bone marrow transplantationand extend prior observations that infusions of donor mononuclearcells are effective therapy for relapsed CML9,11,12. Follow-updata are still limited, but six of the eight patients with stableCML in relapse who were treated have had sustained moleculargenetic remissions, and none have had another relapse. Theseresults are encouraging, since the inability to detect bcr/abltranscripts by PCR after transplantation correlates with relapse-freesurvival10. The therapy was less effective for patients withaccelerated CML.
Myelosuppression and marrow hypoplasia after therapy were oftendramatic and temporally related to the development of acuteGVHD (Figure 3). Their occurrence can be explained by the eliminationof leukemic hematopoiesis mediated by infused donor mononuclearcells before adequate donor hematopoiesis was reestablished.The lack of spontaneous recovery in Patient 3 was probably dueto the presence of insufficient numbers of donor stem cells.Despite the fact that over 99 percent of the blood cells werederived from the donor, marrow hypoplasia persisted in thispatient until additional bone marrow was infused, suggestingthat the total number of stem cells was inadequate to sustainnormal hematopoiesis. It is less likely that the infusion ofdonor bone marrow overcame cellular or humoral suppression ofnormal hematopoiesis, although this possibility cannot be excluded.
Mononuclear cells were administered without prophylactic immunosuppression10 to 56 months after the initial transplantation. This delaymay be responsible for the relatively mild GVHD that occurreddespite the infusion of up to 10 times more T cells than aretypically contained in unmanipulated donor bone marrow13,14,15.Previous attempts to augment the graft-versus-leukemia reactionwith infusions of donor leukocytes in the immediate post-transplantationperiod resulted in more severe GVHD with no improvement in survival;this result was due at least in part to the increased mortalityassociated with GVHD27. GVHD may be less severe when its effectsare separated from the tissue damage induced by the conditioningregimen28. Residual donor lymphocytes also may mediate immunetolerance, further limiting the severity of the GVHD reaction29.
The mechanism of the antileukemic reaction is probably cell-mediatedcytotoxicity. Donor T cells are clearly important in the graft-versus-leukemiareaction,2,6,8 but other types of cells, including monocytes,natural killer cells, and hematopoietic progenitor cells, werealso infused. Although cytotoxic T cells or natural killer cellsmay directly mediate the antileukemic reaction,30 other mononuclearcells may stimulate additional effector cells or cytokines.The target antigens of the antileukemic response are unknownbut could include minor histocompatibility antigens of the hostor possibly CML-specific antigens.
It is unlikely that interferon alfa-2b alone was responsiblefor the observed antileukemic effects. Interferon alfa-2b caninduce occasional cytogenetic remissions when given as primarytherapy for CML,31 but these remissions occur slowly,31 andmolecular genetic remissions have not been documented32. Completecytogenetic remissions have been obtained in a few patientswith relapsed CML treated with interferon alfa-2b alone, althoughhalf ultimately relapsed again; bcr/abl transcripts were stilldetectable in the single patient tested33. No patient in ourstudy had a cytogenetic remission before the infusion of mononuclearcells. However, interferon alfa-2b has antiproliferative effectsand may result in cytoreduction. It may facilitate a cell-mediatedantileukemic reaction directly34,35 or through the inductionof additional cytokines. It can also increase the expressionof major histocompatibility antigens on cells36 and restorethe deficient expression of the adhesion molecule lymphocyte-function-associatedantigen 3 on CML progenitor cells37. However, a similar graft-versus-leukemiareaction has been generated without the use of interferon alfa-2bin some patients11.
For patients with stable CML who have a relapse after allogeneicbone marrow transplantation, interferon alfa-2b and infusionsof donor mononuclear cells can be effective antileukemic therapy.However, the durability of the remissions and the effect onsurvival remain to be determined. This therapy offers an alternativeto a second bone marrow transplantation for patients with CMLwho have a relapse after allogeneic marrow transplantation.
Supported in part by grants from the National Institutes ofHealth (T32-HL07623 to Dr. Porter, CA39542 and CA58661 to Dr.Antin, R29DK43470-02 to Dr. Roth, and AI30018 to Dr. Ferrara)and the American Cancer Society (to Dr. Roth). Dr. Ferrara isa scholar of the Leukemia Society of America.
We are indebted to Dr. Mark A. Goldberg and Dr. Robert I. Handinfor their critical review of the manuscript and many helpfulsuggestions.
Source Information
From the Division of Hematology-Oncology, Brigham and Women's Hospital and Harvard Medical School, Boston (D.L.P., C.M., J.L.M.F., J.H.A.), and the Division of Hematology-Oncology, University of Michigan Medical Center, Ann Arbor (M.S.R.).
Address reprint requests to Dr. Antin at the Division of Hematology-Oncology, Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.
References
McGlave P, Arthur D, Haake R, et al. Therapy of chronic myelogenous leukemia with allogeneic bone marrow transplantation. J Clin Oncol 1987;5:1033-1040. [Free Full Text]
Goldman JM, Gale RP, Horowitz MM, et al. Bone marrow transplantation for chronic myelogenous leukemia in chronic phase: increased risk for relapse associated with T-cell depletion. Ann Intern Med 1988;108:806-814.
Mrsic M, Horowitz MM, Atkinson K, et al. Second HLA-identical sibling transplants for leukemia recurrence. Bone Marrow Transplant 1992;9:269-275. [Medline]
Barnes DWH, Loutit JF. Treatment of murine leukaemia with X-rays and homologous bone marrow. Br J Haematol 1957;3:241-252. [Medline]
Horowitz MM, Gale RP, Sondel PM, et al. Graft-versus-leukemia reactions after bone marrow transplantation. Blood 1990;75:555-562. [Free Full Text]
Sullivan KM, Weiden PL, Storb R, et al. Influence of acute and chronic graft-versus-host disease on relapse and survival after bone marrow transplantation from HLA-identical siblings as treatment of acute and chronic leukemia. Blood 1989;73:1720-1728. [Erratum, Blood 1989;74:1180.] [Free Full Text]
Apperley JF, Mauro FR, Goldman JM, et al. Bone marrow transplantation for chronic myeloid leukaemia in first chronic phase: importance of a graft-versus-leukaemia effect. Br J Haematol 1988;69:239-245. [Medline]
Kolb HJ, Mittermuller J, Clemm C, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood 1990;76:2462-2465. [Free Full Text]
Roth MS, Antin JH, Ash R, et al. Prognostic significance of Philadelphia chromosome-positive cells detected by the polymerase chain reaction after allogeneic bone marrow transplant for chronic myelogenous leukemia. Blood 1992;79:276-282. [Free Full Text]
Cullis JO, Jiang YZ, Schwarer AP, Hughes TP, Barrett AJ, Goldman JM. Donor leukocyte infusions for chronic myeloid leukemia in relapse after allogeneic bone marrow transplantation. Blood 1992;79:1379-1381. [Free Full Text]
Drobyski WR, Roth MS, Thibodeau SN, Gottschall JL. Molecular remission occurring after donor leukocyte infusions for the treatment of relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation. Bone Marrow Transplant 1992;10:301-304. [Medline]
Antin JH, Bierer BE, Smith BR, et al. Selective depletion of bone marrow T lymphocytes with anti-CD5 monoclonal antibodies: effective prophylaxis for graft-versus-host disease in patients with hematologic malignancies. Blood 1991;78:2139-2149. [Free Full Text]
Soiffer RJ, Murray C, Mauch P, et al. Prevention of graft-versus-host disease by selective depletion of CD6-positive T lymphocytes from donor bone marrow. J Clin Oncol 1992;10:1191-1200. [Abstract]
Wagner JE, Santos GW, Noga SJ, et al. Bone marrow graft engineering by counterflow centrifugal elutriation: results of a phase I-II clinical trial. Blood 1990;75:1370-1377. [Free Full Text]
Storb R, Deeg HJ, Whitehead J, et al. Methotrexate and cyclosporine compared with cyclosporine alone for prophylaxis of acute graft versus host disease after marrow transplantation for leukemia. N Engl J Med 1986;314:729-735. [Abstract]
Speck B, Bortin MM, Champlin R, et al. Allogeneic bone-marrow transplantation for chronic myelogenous leukaemia. Lancet 1984;1:665-668. [Medline]
Glucksberg H, Storb R, Fefer A, et al. Clinical manifestations of graft-versus-host disease in human recipients of HL-A-matched sibling donors. Transplantation 1974;18:295-304. [Medline]
Shulman HM, Sullivan KM, Weiden PL, et al. Chronic graft-versus-host syndrome in man: a long-term clinicopathologic study of 20 Seattle patients. Am J Med 1980;69:204-217. [CrossRef][Medline]
Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958;53:457-81.
Adams PT, Davenport RD, Reardon DA, Roth MS. Detection of circulating donor white blood cells in patients receiving multiple transfusions. Blood 1992;80:551-555. [Free Full Text]
Roth MS, Antin JH, Bingham EL, Ginsburg D. Use of polymerase chain reaction-detected sequence polymorphisms to document engraftment following allogeneic bone marrow transplantation. Transplantation 1990;49:714-720. [CrossRef][Medline]
Hendy GN, Kronenberg HM, Potts JT Jr, Rich A. Nucleotide sequence of cloned cDNAs encoding human preproparathyroid hormone. Proc Natl Acad Sci U S A 1981;78:7365-7369. [Free Full Text]
Ferrara JLM, Weinstein HJ, Guinan EC, et al. Phase I/II trial of recombinant human IL-1 receptor antagonist (IL-1ra) for steroid-resistant GVHD. Blood 1992;80:Suppl A:270a-270a.abstract
Shulman HM, Sharma P, Amos D, Fenster LF, McDonald GB. A coded histologic study of hepatic graft-versus-host disease after human bone marrow transplantation. Hepatology 1988;8:463-470. [Medline]
Collins RH Jr, Rogers ZR, Bennett M, Kumar V, Nikein A, Fay JW. Hematologic relapse of chronic myelogenous leukemia following allogeneic bone marrow transplantation: apparent graft-versus-leukemia effect following abrupt discontinuation of immunosuppression. Bone Marrow Transplant 1992;10:391-395. [Medline]
Sullivan KM, Storb R, Buckner CD, et al. Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N Engl J Med 1989;320:828-834. [Abstract]
Antin JH, Ferrara JLM. Cytokine dysregulation and acute graft-versus-host disease. Blood 1992;80:2964-2968. [Free Full Text]
Weiden PL, Storb R, Tsoi MS, Graham TC, Lerner KG, Thomas ED. Infusion of donor lymphocytes into stable canine radiation chimeras: implications for mechanism of transplantation tolerance. J Immunol 1976;116:1212-1219. [Free Full Text]
Hauch M, Gazzola MV, Small T, et al. Anti-leukemia potential of interleukin-2 activated natural killer cells after bone marrow transplantation for chronic myelogenous leukemia. Blood 1990;75:2250-2262. [Free Full Text]
Talpaz M, Kantarjian H, Kurzrock R, Trujillo JM, Gutterman JU. Interferon-alpha produces sustained cytogenetic responses in chronic myelogenous leukemia: Philadelphia chromosome-positive patients. Ann Intern Med 1991;114:532-538.
Opalka B, Wandl UB, Becher R, et al. Minimal residual disease in patients with chronic myelogenous leukemia undergoing long-term treatment with recombinant interferon -2b alone or in combination with interferon gamma. Blood 1991;78:2188-2193. [Free Full Text]
Higano CS, Raskind WH, Singer JW. Use of alpha interferon for the treatment of relapse of chronic myelogenous leukemia in chronic phase after allogeneic bone marrow transplantation. Blood 1992;80:1437-1442. [Free Full Text]
Herberman RB, Ortaldo JR, Rubinstein M, Pestka S. Augmentation of natural and antibody-dependent cell-mediated cytotoxicity by pure human leukocyte interferon. J Clin Immunol 1981;1:149-153. [Medline]
Myers JD, Flournoy N, Sander JE, et al. Prophylactic use of human leukocyte interferon after allogeneic marrow transplantation. Ann Intern Med 1987;107:809-816.
Interferons. In: Balkwill FR. Cytokines in cancer therapy. Oxford, England: Oxford University Press, 1989:8-53.
Upadhyaya G, Guba SC, Sih SA, et al. Interferon-alpha restores the deficient expression of the cytoadhesion molecule lymphocyte function antigen-3 by chronic myelogenous leukemia progenitor cells. J Clin Invest 1991;88:2131-2136.
van der Veken, L. T., Coccoris, M., Swart, E., Falkenburg, J. H. F., Schumacher, T. N., Heemskerk, M. H. M.
(2009). {alpha}{beta} T Cell Receptor Transfer to {gamma}{delta} T Cells Generates Functional Effector Cells without Mixed TCR Dimers In Vivo. J. Immunol.
182: 164-170
[Abstract][Full Text]
Kolb, H.-J.
(2008). Graft-versus-leukemia effects of transplantation and donor lymphocytes. Blood
112: 4371-4383
[Abstract][Full Text]
Bishop, M. R., Dean, R. M., Steinberg, S. M., Odom, J., Pavletic, S. Z., Chow, C., Pittaluga, S., Sportes, C., Hardy, N. M., Gea-Banacloche, J., Kolstad, A., Gress, R. E., Fowler, D. H.
(2008). Clinical evidence of a graft-versus-lymphoma effect against relapsed diffuse large B-cell lymphoma after allogeneic hematopoietic stem-cell transplantation. Ann Oncol
19: 1935-1940
[Abstract][Full Text]
Chen, D.-P., Tseng, C.-P., Tsai, S.-H., Wu, T.-L., Chang, P.-Y., Sun, C.-F.
(2008). Systematic Analysis of Stutters to Enhance the Accuracy of Chimerism Testing. Annals of Clinical & Laboratory Science
38: 264-272
[Abstract][Full Text]
Miller, J. S., Weisdorf, D. J., Burns, L. J., Slungaard, A., Wagner, J. E., Verneris, M. R., Cooley, S., Wangen, R., Fautsch, S. K., Nicklow, R., DeFor, T., Blazar, B. R.
(2007). Lymphodepletion followed by donor lymphocyte infusion (DLI) causes significantly more acute graft-versus-host disease than DLI alone. Blood
110: 2761-2763
[Abstract][Full Text]
Antin, J. H.
(2007). Reduced-Intensity Stem Cell Transplantation: "...whereof a little More than a little is by much too much." King Henry IV, part 1, I, 2. ASH Education Book
2007: 47-54
[Abstract][Full Text]
Porter, D. L., Levine, B. L., Bunin, N., Stadtmauer, E. A., Luger, S. M., Goldstein, S., Loren, A., Phillips, J., Nasta, S., Perl, A., Schuster, S., Tsai, D., Sohal, A., Veloso, E., Emerson, S., June, C. H.
(2006). A phase 1 trial of donor lymphocyte infusions expanded and activated ex vivo via CD3/CD28 costimulation. Blood
107: 1325-1331
[Abstract][Full Text]
Roman, E., Cooney, E., Harrison, L., Militano, O., Wolownik, K., Hawks, R., Foley, S., Satwani, P., Unal, E., Bhatia, M., Bradley, B., Del Toro, G., George, D., Garvin, J., van de Ven, C., Cairo, M. S.
(2005). Preliminary Results of the Safety of Immunotherapy with Gemtuzumab Ozogamicin following Reduced Intensity Allogeneic Stem Cell Transplant in Children with CD33+ Acute Myeloid Leukemia. Clin. Cancer Res.
11: 7164s-7170s
[Abstract][Full Text]
Imai, C., Iwamoto, S., Campana, D.
(2005). Genetic modification of primary natural killer cells overcomes inhibitory signals and induces specific killing of leukemic cells. Blood
106: 376-383
[Abstract][Full Text]
Schrier, R. W., Parikh, C. R.
(2005). Comparison of renal injury in myeloablative autologous, myeloablative allogeneic and non-myeloablative allogeneic haematopoietic cell transplantation. Nephrol Dial Transplant
20: 678-683
[Full Text]
Miklos, D. B., Kim, H. T., Miller, K. H., Guo, L., Zorn, E., Lee, S. J., Hochberg, E. P., Wu, C. J., Alyea, E. P., Cutler, C., Ho, V., Soiffer, R. J., Antin, J. H., Ritz, J.
(2005). Antibody responses to H-Y minor histocompatibility antigens correlate with chronic graft-versus-host disease and disease remission. Blood
105: 2973-2978
[Abstract][Full Text]
DeAngelo, D. J., Hochberg, E. P., Alyea, E. P., Longtine, J., Lee, S., Galinsky, I., Parekkedon, B., Ritz, J., Antin, J. H., Stone, R. M., Soiffer, R. J.
(2004). Extended Follow-up of Patients Treated with Imatinib Mesylate (Gleevec) for Chronic Myelogenous Leukemia Relapse after Allogeneic Transplantation: Durable Cytogenetic Remission and Conversion to Complete Donor Chimerism without Graft-versus-Host Disease. Clin. Cancer Res.
10: 5065-5071
[Abstract][Full Text]
Antin, J. H.
(2003). A 41-Year-Old Woman With Chronic Myelogenous Leukemia. JAMA
290: 1083-1090
[Full Text]
Billiau, A. D., Fevery, S., Rutgeerts, O., Landuyt, W., Waer, M.
(2003). Transient expansion of Mac1+Ly6-G+Ly6-C+ early myeloid cells with suppressor activity in spleens of murine radiation marrow chimeras: possible implications for the graft-versus-host and graft-versus-leukemia reactivity of donor lymphocyte infusions. Blood
102: 740-748
[Abstract][Full Text]
Marks, D. I., Lush, R., Cavenagh, J., Milligan, D. W., Schey, S., Parker, A., Clark, F. J., Hunt, L., Yin, J., Fuller, S., Vandenberghe, E., Marsh, J., Littlewood, T., Smith, G. M., Culligan, D., Hunter, A., Chopra, R., Davies, A., Towlson, K., Williams, C. D.
(2002). The toxicity and efficacy of donor lymphocyte infusions given after reduced-intensity conditioning allogeneic stem cell transplantation. Blood
100: 3108-3114
[Abstract][Full Text]
Perez-Simon, J. A., Kottaridis, P. D., Martino, R., Craddock, C., Caballero, D., Chopra, R., Garcia-Conde, J., Milligan, D. W., Schey, S., Urbano-Ispizua, A., Parker, A., Leon, A., Yong, K., Sureda, A., Hunter, A., Sierra, J., Goldstone, A. H., Linch, D. C., Miguel, J. F. S., Mackinnon, S.
(2002). Nonmyeloablative transplantation with or without alemtuzumab: comparison between 2 prospective studies in patients with lymphoproliferative disorders. Blood
100: 3121-3127
[Abstract][Full Text]
Billiau, A. D., Fevery, S., Rutgeerts, O., Landuyt, W., Waer, M.
(2002). Crucial role of timing of donor lymphocyte infusion in generating dissociated graft-versus-host and graft-versus-leukemia responses in mice receiving allogeneic bone marrow transplants. Blood
100: 1894-1902
[Abstract][Full Text]
Hayashi, S., Peranteau, W. H., Shaaban, A. F., Flake, A. W.
(2002). Complete allogeneic hematopoietic chimerism achieved by a combined strategy of in utero hematopoietic stem cell transplantation and postnatal donor lymphocyte infusion. Blood
100: 804-812
[Abstract][Full Text]
Guglielmi, C., Arcese, W., Dazzi, F., Brand, R., Bunjes, D., Verdonck, L. F., Schattenberg, A., Kolb, H.-J., Ljungman, P., Devergie, A., Bacigalupo, A., Gomez, M., Michallet, M., Elmaagacli, A., Gratwohl, A., Apperley, J., Niederwieser, D.
(2002). Donor lymphocyte infusion for relapsed chronic myelogenous leukemia: prognostic relevance of the initial cell dose. Blood
100: 397-405
[Abstract][Full Text]
Ballen, K. K., Becker, P. S., Emmons, R. V. B., Fitzgerald, T. J., Hsieh, C. C., Liu, Q., Heyes, C., Clark, Y., Levy, W., Lambert, J. F., Chiafari, F., Szymanski, I., Rososhansky, S., Popovsky, M. A., Stewart, F. M., Quesenberry, P. J.
(2002). Low-dose total body irradiation followed by allogeneic lymphocyte infusion may induce remission in patients with refractory hematologic malignancy. Blood
100: 442-450
[Abstract][Full Text]
Levine, J. E., Braun, T., Penza, S. L., Beatty, P., Cornetta, K., Martino, R., Drobyski, W. R., Barrett, A. J., Porter, D. L., Giralt, S., Leis, J., Holmes, H. E., Johnson, M., Horowitz, M., Collins, R. H. Jr
(2002). Prospective Trial of Chemotherapy and Donor Leukocyte Infusions for Relapse of Advanced Myeloid Malignancies After Allogeneic Stem-Cell Transplantation. JCO
20: 405-412
[Abstract][Full Text]
Kang, E. M., de Witte, M., Malech, H., Morgan, R. A., Phang, S., Carter, C., Leitman, S. F., Childs, R., Barrett, A. J., Little, R., Tisdale, J. F.
(2002). Nonmyeloablative conditioning followed by transplantation of genetically modified HLA-matched peripheral blood progenitor cells for hematologic malignancies in patients with acquired immunodeficiency syndrome. Blood
99: 698-701
[Abstract][Full Text]
Maloney, D. G., Sandmaier, B. M., Mackinnon, S., Shizuru, J. A.
(2002). Non-Myeloablative Transplantation. ASH Education Book
2002: 392-421
[Abstract][Full Text]
Yang, X.-F., Wu, C. J., McLaughlin, S., Chillemi, A., Wang, K. S., Canning, C., Alyea, E. P., Kantoff, P., Soiffer, R. J., Dranoff, G., Ritz, J.
(2001). CML66, a broadly immunogenic tumor antigen, elicits a humoral immune response associated with remission of chronic myelogenous leukemia. Proc. Natl. Acad. Sci. USA
98: 7492-7497
[Abstract][Full Text]
McSweeney, P. A., Niederwieser, D., Shizuru, J. A., Sandmaier, B. M., Molina, A. J., Maloney, D. G., Chauncey, T. R., Gooley, T. A., Hegenbart, U., Nash, R. A., Radich, J., Wagner, J. L., Minor, S., Appelbaum, F. R., Bensinger, W. I., Bryant, E., Flowers, M. E. D., Georges, G. E., Grumet, F. C., Kiem, H.-P., Torok-Storb, B., Yu, C., Blume, K. G., Storb, R. F.
(2001). Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects. Blood
97: 3390-3400
[Abstract][Full Text]
Cutler, C., Antin, J. H.
(2001). Peripheral Blood Stem Cells for Allogeneic Transplantation: A Review. Stem Cells
19: 108-117
[Abstract][Full Text]
Storb, R. F., Champlin, R., Riddell, S. R., Murata, M., Bryant, S., Warren, E. H.
(2001). Non-Myeloablative Transplants for Malignant Disease. ASH Education Book
2001: 375-391
[Abstract][Full Text]
Blazar, B. R., Lees, C. J., Martin, P. J., Noelle, R. J., Kwon, B., Murphy, W., Taylor, P. A.
(2000). Host T Cells Resist Graft-Versus-Host Disease Mediated by Donor Leukocyte Infusions. J. Immunol.
165: 4901-4909
[Abstract][Full Text]
Lokhorst, H. M., Schattenberg, A., Cornelissen, J. J., van Oers, M. H. J., Fibbe, W., Russell, I., Donk, N. W. C. J. v. d., Verdonck, L. F.
(2000). Donor Lymphocyte Infusions for Relapsed Multiple Myeloma After Allogeneic Stem-Cell Transplantation: Predictive Factors for Response and Long-Term Outcome. JCO
18: 3031-3037
[Abstract][Full Text]
Craddock, C., Szydlo, R. M., Klein, J. P., Dazzi, F., Olavarria, E., van Rhee, F., Pocock, C., Cwynarski, K., Apperley, J. F., Goldman, J. M.
(2000). Estimating leukemia-free survival after allografting for chronic myeloid leukemia: a new method that takes into account patients who relapse and are restored to complete remission. Blood
96: 86-90
[Abstract][Full Text]
Bishop, M. R., Tarantolo, S. R., Pavletic, Z. S., Lynch, J. C., Morris, M. E., Zacharias, D., Armitage, J. O., Kessinger, A.
(2000). Filgrastim as an Alternative to Donor Leukocyte Infusion for Relapse After Allogeneic Stem-Cell Transplantation. JCO
18: 2269-2272
[Abstract][Full Text]
Guglielmi, C., Arcese, W., Hermans, J., Bacigalupo, A., Bandini, G., Bunjes, D., Carreras, E., Devergie, A., Frassoni, F., Goldman, J., Gratwohl, A., Kolb, H.-J., Iori, A. P., Niederwieser, D., Prentice, H. G., de Witte, T., Apperley, J.
(2000). Risk assessment in patients with Ph+ chronic myelogenous leukemia at first relapse after allogeneic stem cell transplant: an EBMT retrospective analysis. Blood
95: 3328-3334
[Abstract][Full Text]
Georges, G. E., Storb, R., Thompson, J. D., Yu, C., Gooley, T., Bruno, B., Nash, R. A.
(2000). Adoptive immunotherapy in canine mixed chimeras after nonmyeloablative hematopoietic cell transplantation. Blood
95: 3262-3269
[Abstract][Full Text]
Porter, D. L., Collins, R. H. Jr, Hardy, C., Kernan, N. A., Drobyski, W. R., Giralt, S., Flowers, M. E.D., Casper, J., Leahey, A., Parker, P., Mick, R., Bate-Boyle, B., King, R., Antin, J. H.
(2000). Treatment of relapsed leukemia after unrelated donor marrow transplantation with unrelated donor leukocyte infusions. Blood
95: 1214-1221
[Abstract][Full Text]
Dazzi, F., Szydlo, R. M., Craddock, C., Cross, N. C. P., Kaeda, J., Chase, A., Olavarria, E., van Rhee, F., Kanfer, E., Apperley, J. F., Goldman, J. M.
(2000). Comparison of single-dose and escalating-dose regimens of donor lymphocyte infusion for relapse after allografting for chronic myeloid leukemia. Blood
95: 67-71
[Abstract][Full Text]
Gao, L., Yang, T.-H., Tourdot, S., Sadovnikova, E., Hasserjian, R., Stauss, H. J.
(1999). Allo-Major Histocompatibility Complex-Restricted Cytotoxic T Lymphocytes Engraft in Bone Marrow Transplant Recipients Without Causing Graft-Versus-Host Disease. Blood
94: 2999-3006
[Abstract][Full Text]
Engels, F. H. C., Koski, G. K., Bedrosian, I., Xu, S., Luger, S., Nowell, P. C., Cohen, P. A., Czerniecki, B. J.
(1999). Calcium signaling induces acquisition of dendritic cell characteristics in chronic myelogenous leukemia myeloid progenitor cells. Proc. Natl. Acad. Sci. USA
96: 10332-10337
[Abstract][Full Text]
Falkenburg, J.H. F., Wafelman, A. R., Joosten, P., Smit, W. M., van Bergen, C. A.M., Bongaerts, R., Lurvink, E., van der Hoorn, M., Kluck, P., Landegent, J. E., Kluin-Nelemans, H. C., Fibbe, W. E., Willemze, R.
(1999). Complete Remission of Accelerated Phase Chronic Myeloid Leukemia by Treatment With Leukemia-Reactive Cytotoxic T Lymphocytes. Blood
94: 1201-1208
[Abstract][Full Text]
Drobyski, W. R., Hessner, M. J., Klein, J. P., Kabler-Babbitt, C., Vesole, D. H., Keever-Taylor, C. A.
(1999). T-Cell Depletion Plus Salvage Immunotherapy With Donor Leukocyte Infusions as a Strategy to Treat Chronic-Phase Chronic Myelogenous Leukemia Patients Undergoing HLA-Identical Sibling Marrow Transplantation. Blood
94: 434-441
[Abstract][Full Text]
Sawyers, C. L.
(1999). Chronic Myeloid Leukemia. NEJM
340: 1330-1340
[Full Text]
Porter, D. L., Connors, J. M., Van Deerlin, V. M.D., Duffy, K. M., McGarigle, C., Saidman, S. L., Leonard, D. G.B., Antin, J. H.
(1999). Graft-Versus-Tumor Induction With Donor Leukocyte Infusions as Primary Therapy for Patients With Malignancies. JCO
17: 1234-1234
[Abstract][Full Text]
Fernandez-Herrera, J., Valks, R., Feal, C., Fraga, J., Tomas, J. F., Garcia-Diez, A.
(1999). Induction of Hyperacute Graft-vs-Host Disease After Donor Leukocyte Infusions. Arch Dermatol
135: 304-308
[Abstract][Full Text]
Smit, W. M., Rijnbeek, M., van Bergen, C. A. M., Fibbe, W. E., Willemze, R., Falkenburg, J. H. F.
(1998). T cells recognizing leukemic CD34+ progenitor cells mediate the antileukemic effect of donor lymphocyte infusions for relapsed chronic myeloid leukemia after allogeneic stem cell transplantation. Proc. Natl. Acad. Sci. USA
95: 10152-10157
[Abstract][Full Text]
Chen, W., Chatta, G. S., Rubin, W. D., Clark, J. G., Hackman, R. C., Madtes, D. K., Ligitt, D. H., Kusunoki, Y., Martin, P. J., Cheever, M. A.
(1998). T Cells Specific for a Polymorphic Segment of CD45 Induce Graft-Versus-Host Disease with Predominant Pulmonary Vasculitis. J. Immunol.
161: 909-918
[Abstract][Full Text]
Mori, T., Nishimura, T., Ikeda, Y., Hotta, T., Yagita, H., Ando, K.
(1998). Involvement of Fas-Mediated Apoptosis in the Hematopoietic Progenitor Cells of Graft-Versus-Host Reaction-Associated Myelosuppression. Blood
92: 101-107
[Abstract][Full Text]
Alyea, E. P., Soiffer, R. J., Canning, C., Neuberg, D., Schlossman, R., Pickett, C., Collins, H., Wang, Y., Anderson, K. C., Ritz, J.
(1998). Toxicity and Efficacy of Defined Doses of CD4+ Donor Lymphocytes for Treatment of Relapse After Allogeneic Bone Marrow Transplant. Blood
91: 3671-3680
[Abstract][Full Text]
Warren, E. H., Greenberg, P. D., Riddell, S. R.
(1998). Cytotoxic T-Lymphocyte-Defined Human Minor Histocompatibility Antigens With a Restricted Tissue Distribution. Blood
91: 2197-2207
[Abstract][Full Text]
Papadopoulos, E. B., Carabasi, M. H., Castro-Malaspina, H., Childs, B. H., Mackinnon, S., Boulad, F., Gillio, A. P., Kernan, N. A., Small, T. N., Szabolcs, P., Taylor, J., Yahalom, J., Collins, N. H., Bleau, S. A., Black, P. M., Heller, G., Reilly, R. J. O', Young, J. W.
(1998). T-Cell-Depleted Allogeneic Bone Marrow Transplantation as Postremission Therapy for Acute Myelogenous Leukemia: Freedom From Relapse in the Absence of Graft-Versus-Host Disease. Blood
91: 1083-1090
[Abstract][Full Text]
Lokhorst, H.M., Schattenberg, A., Cornelissen, J.J., Thomas, L.L.M., Verdonck, L.F.
(1997). Donor Leukocyte Infusions Are Effective in Relapsed Multiple Myeloma After Allogeneic Bone Marrow Transplantation. Blood
90: 4206-4211
[Abstract][Full Text]
Higano, C. S., Chielens, D., Raskind, W., Bryant, E., Flowers, M. E.D., Radich, J., Clift, R., Appelbaum, F.
(1997). Use of alpha -2a-Interferon to Treat Cytogenetic Relapse of Chronic Myeloid Leukemia After Marrow Transplantation. Blood
90: 2549-2554
[Abstract][Full Text]
Bonini, C., Ferrari, G., Verzeletti, S., Servida, P., Zappone, E., Ruggieri, L., Ponzoni, M., Rossini, S., Mavilio, F., Traversari, C., Bordignon, C.
(1997). HSV-TK Gene Transfer into Donor Lymphocytes for Control of Allogeneic Graft-Versus-Leukemia. Science
276: 1719-1724
[Abstract][Full Text]
Keil, F., Haas, O. A., Fritsch, G., Kalhs, P., Lechner, K., Mannhalter, C., Reiter, E., Niederwieser, D., Hoecker, P., Greinix, H. T.
(1997). Donor Leukocyte Infusion for Leukemic Relapse After Allogeneic Marrow Transplantation: Lack of Residual Donor Hematopoiesis Predicts Aplasia. Blood
89: 3113-3117
[Abstract][Full Text]
Lee, S. J., Wegner, S. A., McGarigle, C. J., Bierer, B. E., Antin, J. H.
(1997). Treatment of Chronic Graft-Versus-Host Disease With Clofazimine. Blood
89: 2298-2302
[Abstract][Full Text]
Munshi, N.C., Govindarajan, R., Drake, R., Ding, L.M., Iyer, R., Saylors, R., Kornbluth, J., Marcus, S., Chiang, Y., Ennist, D., Kwak, L., Reynolds, C., Tricot, G., Barlogie, B.
(1997). Thymidine Kinase (TK) Gene-Transduced Human Lymphocytes Can Be Highly Purified, Remain Fully Functional, and Are Killed Efficiently With Ganciclovir. Blood
89: 1334-1340
[Abstract][Full Text]
Woo, S.-B., Lee, S. J., Schubert, M. M.
(1997). Graft-vs.-Host Disease. CROBM
8: 201-216
[Abstract][Full Text]
Toren, A, Rechavi, G, Nagler, A
(1996). Minimal residual disease post-bone marrow transplantation for hemato- oncological diseases. Stem Cells
14: 300-311
[Abstract]
Walter, E. A., Greenberg, P. D., Gilbert, M. J., Finch, R. J., Watanabe, K. S., Thomas, E. D., Riddell, S. R.
(1995). Reconstitution of Cellular Immunity against Cytomegalovirus in Recipients of Allogeneic Bone Marrow by Transfer of T-Cell Clones from the Donor. NEJM
333: 1038-1044
[Abstract][Full Text]
Parker, R. I., Nguyen, P. L.
(1994). Case 37-1994- A Newborn Boy with Petechiae, Hepatosplenomegaly, Leukocytosis, and Thrombocytopenia. NEJM
331: 1005-1012
[Full Text]
-2b alone or in combination with interferon gamma. Blood 1991;78:2188-2193. 
Previous
