Long-term follow-up of allogeneic marrow transplants in patients with aplastic anemia conditioned by cyclophosphamide combined with antithymocyte globulin.
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Adolescent↗
Biomedical subjects
F R Appelbaum
Publications and source records attributed to F R Appelbaum.
Acute myeloid leukemia in the elderly: assessment of multidrug resistance (MDR1) and cytogenetics distinguishes biologic subgroups with remarkably distinct responses to standard chemotherapy. A Southwest Oncology Group study.
Compared with younger patients, elderly patients with acute myeloid leukemia (AML) respond poorly to conventional chemotherapy. To determine if this poor response is due to differences in the biologic characteristics of AML in the elderly, we studied 211 patients (161 de novo, 50 secondary AML) over 55 years of age (median, 68 years) registered to a single clinical trial for previously untreated AML (SWOG 9031, Phase III randomized trial of standard dose cytosine arabinoside and daunomycin + rhG-CSF). Pretreatment leukemic blasts were karyotyped and were also analyzed for intrinsic drug resistance by quantitating expression of the multidrug resistance glycoprotein MDR1 and functional drug efflux using sensitive flow cytometric techniques. Results were correlated with clinical variables and outcome. These elderly AML patients had a high frequency of unfavorable cytogenetics (32%), MDR1 protein expression (71%), and functional drug efflux (58%); each of these factors occurred at high frequencies in both de novo and secondary AML patients and was associated with a significantly poorer complete remission (CR) rate. In multivariate analysis, secondary AML (P = .0035), unfavorable cytogenetics (P = .0031), and MDR1 (P = .0041) were each significantly and independently associated with lower CR rates. Resistant disease was associated with unfavorable cytogenetics (P = .017) and MDR1 expression (P = .0007). Strikingly, elderly MDR1(-) de novo AML patients with favorable/intermediate cytogenetics had a CR rate of 81%; with increasing MDR1 expression, CR rate decreased in this cytogenetic group. MDR1(+) secondary AML patients with unfavorable cytogenetics had a CR rate of only 12%. Thus, AML in the elderly is associated with an increased frequency of unfavorable cytogenetics and MDR1 expression, both of which independently contribute to poor outcomes. The high frequencies of these features in both de novo and secondary elderly AML patients suggest a common biologic mechanism for these leukemias distinct from that in younger patients. Investigation of biologic parameters at diagnosis in AML in the elderly may help identify patients with a high likelihood of achieving CR with conventional regimens, as well as those who may require alternate regimens designed to overcome therapy resistance.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Marrow transplantation for chronic myeloid leukemia: the influence of plasma busulfan levels on the outcome of transplantation.
The influence of busulfan (BU) plasma concentration on outcome of transplantation from HLA identical family members for the treatment of chronic myelogenous leukemia (CML) was examined in 45 patients transplanted in chronic phase (CP) (n = 39) or accelerated phase (AP) (n = 6). All patients received the same regimen of BU, 16 mg/kg orally and cyclophosphamide (CY), 120 mg/kg intravenously. Plasma concentrations of BU at steady state (C(SS)BU) during the dosing interval were measured for each patient. The mean C(SS)BU was 917 ng/mL (range, 642 to 1,749; median, 917; standard deviation, 213). Of patients with C(SS)BU below the median, seven (five of 18 in CP and two of four in AP) developed persistent cytogenetic relapse and three of these patients died. There were no relapses in patients with C(SS)BU above the median. The difference in the cumulative incidence of relapse between the two groups was statistically significant (P = .0003). C(SS)BU was the only statistically significant determinant of relapse in univariable or multivariable analysis. The 3-year survival estimates were 0.82 and 0.64 for patients with C(SS)BU above and below the median (P = .33). There was no statistically significant association of C(SS)BU with survival or nonrelapse mortality, although the power to detect a difference in survival between 0.82 and 0.64 was only 0.24, similarly C(SS)BU above the median was not associated with an increased risk of severe regimen-related toxicity. We conclude that low BU plasma levels are associated with an increased risk of relapse.
Adult↗
Stem cell transplantation for secondary acute myeloid leukemia: evaluation of transplantation as initial therapy or following induction chemotherapy.
The purpose of this report is to describe the results of stem cell transplantation as initial treatment for secondary acute myeloid leukemia (AML). Forty-six patients (median age 42 years) with secondary AML (17 therapy-related, 29 myelodysplasia-related) who had not received remission induction chemotherapy underwent allogeneic (n = 43) or syngeneic (n = 3) transplantation. The 5-year actuarial disease-free survival was 24.4%, and the cumulative incidences of relapse and nonrelapse mortality were 31.3% and 44.3%, respectively. Lower peripheral blood blast count was associated with a lower risk of relapse (P = .05) and shorter time from AML diagnosis to transplant was associated with a lower risk of nonrelapse mortality (P = .02) and improved disease-free survival (P = .026). Patients with therapy-related secondary AML tended to have lower disease-free survival (P = .16) and a higher relapse rate (P = .16) than patients whose leukemia was not therapy-related. The results of these 46 previously untreated patients were compared to 20 patients (median age 36 years, 12 therapy-related, 8 myelodysplasia-related) transplanted with chemotherapy-sensitive disease after induction chemotherapy (first complete remission [n = 6], second complete remission [n = 3], first untreated relapse [n = 11]). We found no statistically significant difference in outcome between these 2 groups of patients. These results suggest that prompt transplantation should be considered after diagnosis of secondary AML or, if possible, high-risk myelodysplasia, particularly in patients with low peripheral blast counts. Innovative transplant strategies are needed to reduce the high risks of relapse and nonrelapse mortality seen in this patient population.
Adolescent↗
Detection of bcr-abl transcripts in Philadelphia chromosome-positive acute lymphoblastic leukemia after marrow transplantation.
Thirty-six patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) were studied for the presence of the bcr-abl fusion mRNA transcript after an allogeneic matched related (N = 12), partially matched related (N = 4), matched unrelated (N = 14), autologous (N = 5), or syngeneic (N = 1) bone marrow transplant (BMT). Seventeen were transplanted in relapse, and 19 were transplanted in remission. Twenty-three patients had at least one positive bcr-abl polymerase chain reaction (PCR) assay after BMT either before a relapse or without subsequent relapse. Ten of these 23 relapsed after a positive assay at a median time from first positive PCR assay of 94 days (range, 28 to 416 days). By comparison, only 2 relapses occurred in the 13 patients with no prior positive PCR assays; both patients had missed at least one scheduled follow-up assay and were not tested 2 months and 26 months before their relapse. The unadjusted relative risk (RR) of relapse associated with a positive PCR assay compared with a negative assay was 5.7 (95% confidence interval 1.2 to 26.0, P = .025). In addition, the data suggest that the type of bcr-abl chimeric mRNA detected posttransplant was associated with the risk of relapse: 7 of 10 patients expressing the p190 bcr-abl relapsed, compared with 1 of 8 who expressed only the p210 bcr-abl mRNA (P = .02, log-rank test). The RR of p190 bcr-abl positivity compared to PCR-negative patients was 11.2 (confidence interval 2.3-54.8, P = 0.003), whereas a positive test for p210 bcr-abl was apparently not associated with an increased relative risk. In separate multivariable models, PCR positivity remained a statistically significant risk factor for relapse after separately adjusting for donor (unrelated and partially matched v matched, autologous, and syngeneic), remission status at the time of transplant, the presence of acute graft-versus-host disease (GVHD), and type of conditioning regimen (total body irradiation dose of < or = 1,200 cGy v > 1,200 cGy). The PCR assay appears to be a useful test for predicting patients at high risk of relapse after BMT and may identify patients who might benefit from therapeutic interventions. The finding that the expression of p190 bcr-abl may portend an especially high risk of relapse suggests a different clinical and biologic behavior between p190 and p210 bcr-abl.
Acute Disease↗
Primary treatment of acquired aplastic anemia: outcomes with bone marrow transplantation and immunosuppressive therapy. Seattle Bone Marrow Transplant Team.
BACKGROUND: Both immunosuppressive therapy and bone marrow transplantation are accepted treatments for patients with aplastic anemia. Choosing one of these therapies for a given patient depends not only on donor availability but also on such factors as patient age. OBJECTIVE: To compare survival rates and long-term complications after bone marrow transplantation or immunosuppressive therapy in patients with acquired aplastic anemia and to identify prognostic factors associated with improved survival. DESIGN: Center-based, retrospective analysis. SETTING: Referral center for patients with aplastic anemia. PATIENTS: 395 patients with acquired aplastic anemia. INTERVENTION: Bone marrow transplant from an HLA-identical, related donor or immunosuppressive therapy. MEASUREMENTS: Kaplan-Meier survival curves, results of log rank tests, and cumulative incidence curves. RESULTS: Of 168 bone marrow transplant recipients, 89% had sustained engraftment. Forty-six patients developed grade II to IV acute graft-versus-host disease, and 68 developed chronic graft-versus-host disease that required therapy. Of 227 patients who received immunosuppressive therapy, 44% achieved a complete, partial, or minimal response. Fifty-four percent died or had no response to therapy. Actuarial survival at 15 years was 69% for bone marrow transplant recipients and 38% for patients receiving immunosuppressive therapy (P < 0.001). Improved survival was associated with having bone marrow transplantation as primary therapy, being younger, having no transfusion before transplantation, and having a higher absolute neutrophil count. Disease duration, year of therapy, sex, refractoriness to platelet transfusions, and previous treatment with androgens or corticosteroids did not significantly affect survival. CONCLUSIONS: Data from this center suggest that bone marrow transplantation may be preferred for younger patients with acquired aplastic anemia who have matched, related donors. Long-term survival is excellent for patients who respond to either form of therapy.
Actuarial Analysis↗
Measurement of spontaneous and therapeutic agent-induced apoptosis with BCL-2 protein expression in acute myeloid leukemia.
We have designed in vitro assays to investigate the possible association between apoptosis and chemotherapeutic sensitivity in acute myeloid leukemias (AMLs). Consistent low levels of spontaneous apoptosis were observed in myeloid cells from normal bone marrow samples, while untreated cells collected from 56 de novo AML patients showed variable apoptosis. Control myeloid cells showed increased apoptosis after in vitro treatments with daunomycin (DNR), cytosine arabinoside (ARA-C), or gamma irradiation (RAD). Most AML samples showed less treatment-associated apoptosis, suggesting that apoptosis responses to therapeutic agents may be frequently attenuated in AML. Certain cytogenetic abnormalities common in AML may affect apoptosis, as acute promyelocytic leukemia (APL) samples with t(15;17) karyotypes showed consistently low levels of spontaneous and treatment-associated apoptosis. Apoptosis assays may provide unique functional subtyping of AMLs, as other common cytogenetic subsets showed variable apoptosis. Altered function of two well-characterized regulators of apoptosis, BCL-2 and p53, was not entirely responsible for this variability. A genomic p53 mutation was found in only one AML sample. All samples that demonstrated the highest BCL-2-positive cell fractions showed low apoptosis, but reduced apoptosis was seen in both the presence and absence of BCL-2 overexpression. Finally, data from matched diagnosis and relapse sample pairs suggest that neither further reduced apoptosis nor additional BCL-2 overexpression is necessarily associated with disease progression.
Acute Disease↗
The use of radiolabeled antibodies in bone marrow transplantation for hematologic malignancies.
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Antibodies↗
Interleukin-2 after autologous stem cell transplantation for hematologic malignancy: a phase I/II study.
The success of autologous stem cell transplantation (ASCT) for hematologic malignancy is limited largely by a high relapse rate. It is postulated that IL-2 administered after ASCT may eliminate minimal residual disease and thereby reduce relapses. A phase I/II study was performed to identify a regimen of IL-2 (Chiron) that could be given early after ASCT in phase III trials. In the phase I study, beginning a median of 46 days after ASCT for hematologic malignancy, cohorts of three to four patients received escalating doses of 'induction' IL-2 of 9, 10, or 12 x 10(6) IU/m2/day for 4 or 5 days by continuous i.v. infusion (CIV), followed by a 4-day rest period, and then 1.6 x 10(6) IU/m2/day of maintenance IL-2 by CIV for 10 days. The maximum tolerated dose (MTD) of induction IL-2 was 9 x 10(6) IU/m2/day x 4. In the phase II study, 52 patients received the MTD. Eighty percent of patients completed induction IL-2. Most patients exhibited some degree of capillary leak. One patient died of CMV pneumonia and one died of ARDS. Maintenance IL-2 was well tolerated. In the phase I/II study, 16 of 31 patients with non-Hodgkin lymphoma (NHL), 3/8 with Hodgkin disease (HD), 4/17 with AML, and 4/5 with ALL remain in CR. Two of six multiple myeloma (MM) patients remain in PR. Although the regimen of IL-2 identified had significant side-effects in some patients, it was well tolerated in the majority of patients. Phase III prospectively randomized clinical trials are in progress to determine if this IL-2 regimen will decrease the relapse rate after ASCT for AML and NHL.
Adjuvants, Immunologic↗
High-dose busulfan, melphalan, thiotepa and peripheral blood stem cell infusion for the treatment of metastatic breast cancer.
The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.
Adult↗
Allogeneic marrow transplantation for primary myelofibrosis and myelofibrosis secondary to polycythaemia vera or essential thrombocytosis.
Primary myelofibrosis is a clonal haemopoietic disorder, incurable with conventional therapy, and associated with a median survival of 4-5 years. Patients with polycythaemia vera and essential thrombocytosis who progress into a myelofibrotic picture also have a poor prognosis. Between 1980 and 1996, 13 patients with myelofibrosis due to one of these three myeloproliferative disorders (primary myelofibrosis [n=8], essential thrombocytosis [n=3], polycythaemia vera [n=2]) underwent allogeneic marrow transplantation in Seattle. The median age was 40 years (range 18-49). The median time from myeloproliferative diagnosis to transplantation was 39 months (range 5-192). Three patients received preparative regimens containing total body irradiation and 10 received busulphan-cyclophosphamide regimens. Nine patients received marrow from HLA-matched related donors, one from a one antigen mismatched related donor, and three from HLA-matched unrelated donors. The median time to both granulocyte and platelet engraftment was 21 d. Nine patients survive between 1.2 and 7.1 years post-transplant. Two patients relapsed at 1 year post-transplant, both of whom survive in a chronic myeloproliferative state. Four patients died of transplant-related complications between 43 d and 2.2 years post-transplant. At 1 year post-transplant the majority of the disease-free survivors have normal peripheral blood counts and none-to-minimal marrow fibrosis. These preliminary results are encouraging, and suggest that stem cell transplantation can be curative therapy for selected patients with myelofibrosis.
Adolescent↗
Myelodysplasia and myeloproliferative disorders.
Myelodysplasia and the myeloproliferative disorders are clonal hematopoietic stem cell disorders with heterogeneous clinical presentations and prognoses. This review highlights some of the recent progress that has been made in these disorders. Specifically, a number of studies have enhanced our understanding of the pathogenesis of these disorders, and potentially useful animal models for primary myelofibrosis have been developed. New, clinically useful prognostic scoring systems have been devised for myelodysplasia and for primary myelofibrosis. New chemotherapeutic approaches and nonmyelosuppressive alternative therapies for myelodysplasia have been studied. Data on the use of interferon for polycythemia vera and the potential leukemogenesis of hydroxyurea have recently become available. Finally, continued progress has been made in the use of allogeneic (related and unrelated donor) and autologous stem cell transplantation for myelodysplasia.
Humans↗
Effect of different chemotherapy regimens on peripheral-blood stem-cell collections in patients with breast cancer receiving granulocyte colony-stimulating factor.
PURPOSE: To evaluate the effects of chemotherapy regimens on peripheral-blood stem-cell (PBSC) yields in patients with breast cancer who receive granulocyte colony-stimulating factor (G-CSF). PATIENTS AND METHODS: One hundred patients with breast cancer received cyclophosphamide 4 g/m2 for dose (CY) (n = 10), CY and etoposide 600 mg/m2 (CE) (n = 13), CE and cisplatin 105 mg/m2 (CEP) (n = 19), or CY and paclitaxel 170 mg/m2 (n = 58), followed by G-CSF. PBSC collections were initiated when the WBC count recovered to greater than 1 x 10(9)/L. A multivariate analysis was undertaken to evaluate the effects of different chemotherapy regimens and patient variables on PBSC collections as measured by the yield of CD34+ cells. RESULTS: The medians of average daily CD34+ cell yields for patients who received paclitaxel plus CY, CE, and CEP with G-CSF were 12.9, 11.03, and 5.37 x 10(6)/kg, respectively, compared with 2.02 x 10(6)/kg in the reference group that received CY with G-CSF (P = < .0001, .002, and .09, respectively). On first-day collections, patients who received paclitaxel plus CY, CE, and CEP with G-CSF yielded medians of 11.07, 8.09, and 3.52 x 10(6) CD34+ cells/kg, respectively, compared with 0.90 x 10(6)/kg in the reference group that received CY with G-CSF (P = .0006, .02, and .09, respectively). The number of previous cycles of chemotherapy, previous radiotherapy, marrow involvement, and phase and stage of disease did not have statistically significant effects on CD34+ cell yield. CONCLUSION: Combination chemotherapy regimens were superior to single-agent CY for the mobilization of CD34+ cells.
Antigens, CD34↗
Allogeneic hematopoietic stem cell transplantation for acute leukemia.
Allogeneic transplantation is the only form of therapy that enables physicians to cure patients with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) who do not respond to induction therapy. Thus, patients and family members should be human leukocyte antigen (HLA)-typed soon after the diagnosis to expedite transplantation should induction therapy fail. Transplantation is superior to chemotherapy in patients with AML in second remission. The role of transplantation in ALL other than induction failure is somewhat different in children than in adults. Transplantation appears to be the treatment of choice in children with ALL in second remission regardless of the characteristics of the disease. Adults who relapse off-therapy after prolonged remission should probably be reinduced, whereas those with short remissions probably should go directly to transplant. Transplants from family members incompatible for one antigen result in survival rates similar to those observed with HLA-identical sibling transplants, but transplants from family donors mismatched for two or three antigens have been associated with a substantial increase in graft-versus-host disease (GVHD) and other complications and such transplants should be reserved for patients with few other prospects for cure. Randomized trials are underway to compare peripheral blood stem cells mobilized with granulocyte colony stimulating factor to marrow for H LA-matched transplantation. Results with unrelated donor transplants have improved with time and are approaching those for matched sibling transplants. Early results suggest that umbilical cord blood transplants are feasible with more graft failure but less GVHD than with unmodified marrow.
Acute Disease↗
Allogeneic stem cell transplantation for the treatment of hematologic malignancies: current indications and challenges.
Allogeneic stem cell transplantation is a potentially curative treatment for hematologic malignancies. Research efforts are expanding the acceptable donor pool to increase patient access to this form of therapy. Potential sources besides HLA matched siblings include partially mismatched family members, unrelated volunteers, and cord blood stem cells. Although allogeneic hematopoietic stem cell (ASC) transplantation may cure hematologic malignancies, relapse remains a problem. To prevent relapse after transplant, research efforts are focused on optimizing the delivery of systemic chemoradiotherapy, including strategies for targeting therapy to sites of disease, and augmenting the antileukemic effect of the allogeneic graft. It is a challenge to maintain clinical research in the current environment of limited resources, so new paradigms for support of this work may need consideration.
Clinical Trials as Topic↗
Graft versus leukemia (GVL) in the therapy of acute lymphoblastic leukemia (ALL).
The ability of T cells that accompany or develop from transplanted allogeneic marrow to eradicate leukemia has been repeatedly demonstrated in animal models. Whether a similar graft-versus-leukemia effect exists in humans who have received transplants for acute lymphoblastic leukemia can be addressed by five different clinical observations: comparisons of autologous versus allogeneic transplantation, comparisons of syngeneic versus allogeneic transplantation, examination of relapse rates in allogeneic recipients who do or do not develop GVHD, the impact of T-cell depletion on relapse rates, and the results of donor lymphocyte infusions to treat posttransplant relapse. The bulk of available evidence supports the view that a potent GVL effect exists in patients treated for ALL. These results provide a strong rationale for efforts to develop techniques to further capitalize on the GVL effect.
Bone Marrow Transplantation↗
Effect of recombinant canine stem cell factor, a c-kit ligand, on hematopoietic recovery after DLA-identical littermate marrow transplants in dogs.
We studied the effect of recombinant canine stem cell factor (rcSCF) on hematopoietic recovery, incidence of graft failure, graft-vs.-host disease (GVHD), and survival after marrow transplantation from dog leukocyte antigen (DLA)-identical canine littermates. Ten animals received 100 microg rcSCF/kg/day b.i.d. by subcutaneous injection on days 1 through 10 after 920 cGy total body irradiation and transplantation of a mean of 3.7x10(8) marrow cells/kg body weight. None of the dogs received GVHD prophylaxis. All animals showed hematopoietic engraftment. The median number of days to achieve 1000 neutrophils/mm3 was 9; 100 monocytes/mm3 were reached after 15 days, 500 lymphocytes/mm3 after 21 days, and 20,000 platelets/mm3 after 16 days. One animal developed GVHD involving skin, gut, and liver and died of bacterial pneumonia 21 days after transplantation. The remaining nine dogs were observed for a median of 37 days (range 29-84 days) posttransplantation until they were killed. Facial edema was seen in three dogs during the first 2-3 days of rcSCF administration. These results show that within the limits of this study it appears to be safe to administer SCF after DLA-identical littermate marrow transplants in dogs. Comparison with previously published data in the same model showed that neutrophil and monocyte recovery was significantly faster in dogs receiving SCF treatment compared with dogs without growth factor treatment (recovery to achieve 1000 neutrophils/mm3: median 9 days vs. 13 days, p = 0.002; recovery to 100 monocytes/mm3: median 15 days vs. 105 days, p = 0.0002). Otherwise, no significant differences were seen. Results obtained with SCF treatment were similar to those previously obtained in the same model with recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment except that recovery of lymphocytes to 500/mm3 appeared to be more rapid in G-CSF-treated dogs (median 15 days vs. 21 days, p = 0.03).
Animals↗
Methotrexate and cyclosporine for graft-vs.-host disease prevention: what length of therapy with cyclosporine?
One hundred three patients with leukemia, aplastic anemia, or myelodysplastic syndrome were treated by marrow transplantation from genotypically HLA-identical siblings (n = 92) or HLA haploidentical family members differing for one HLA antigen on the nonshared haplotype (n = 11). To prevent graft-vs.-host disease (GVHD), they were administered postgrafting immunosuppression with a short course of intermittent methotrexate with daily cyclosporine for no more than 11 days. Customarily, we have given cyclosporine for 180 days after transplant. In the current study, we asked whether cyclosporine could be stopped earlier without affecting the risk of chronic GVHD. By day 60, patients who never had acute GVHD, or whose acute GVHD had resolved, were randomized to have cyclosporine stopped (n = 52) or continued for the usual 180 days (n = 51). Results were analyzed with a median follow-up of 9.3 years after transplant, and showed that patients in whom cyclosporine was discontinued on day 60 had a significantly more rapid onset (p = 0.001), but not a significantly higher overall incidence of chronic GVHD than those in whom the drug was stopped on day 180 (43 vs. 54%; p = 0.26). Transplant-related mortality was comparable among patients without preceding acute GVHD, regardless of when cyclosporine was discontinued (11% for both study arms). However, transplant-related mortality appeared to increase among patients with preceding acute GVHD in whom cyclosporine was stopped by day 60 (38 vs. 17%). Results suggest that cyclosporine can safely be discontinued early in patients who never had evidence of acute GVHD, while those with preceding acute GVHD would benefit from a longer course of the drug. Because of the relatively small sample sizes, these results would best be treated as promising preliminary findings that should be confirmed in larger randomized studies.
Adult↗