Autologous stem cell transplantation for acute myeloid leukemia

Autologous bone marrow transplant (ABMT) and stem cell transplantation (ASCT) are important treatment modalities for acute myeloid leukemia (AML). The role of ASCT in first remission patients remains controversial. Phase II and phase III studies demonstrate that patients with favorable-risk cytogenetics benefit from ASCT, with reduction in relapse and improvement in leukemia-free survival (LFS). Patients with poor-risk cytogenetics do not appear to benefit significantly from ASCT and should preferentially be treated with allogeneic transplant. The role of ASCT for patients with intermediate risk disease is uncertain. It appears that ASCT in first remission will improve disease-free survival compared to standard chemotherapy. Sufficient patients who relapse after chemotherapy treatment can be salvaged with ASCT in second remission such that the beneficial effect on overall survival is blunted. ASCT produces equivalent results to ABMT but with reduced morbidity. The collection of stem cells during recovery from intensive dose consolidation therapy appears to be an attractive strategy that can increase the percentage of patients who are able to receive their intended transplant. Consolidation therapy prior to stem cell collection and transplant has been shown to decrease the relapse rate and improve outcomes, but the optimal nature of this consolidation therapy is unknown. For patients with AML in second remission, ABMT/ASCT offers a substantial salvage rate, and is particularly effective for patients with acute promyelocytic leukemia.     

Bone marrow transplantation for acute leukemia: recent advances and comparison with alternative therapies

Bone marrow transplantation is an effective therapy in patients with acute leukemia. High-dose chemotherapy with or without total body irradiation and allogeneic bone marrow transplantation is a more effective antileukemic treatment than chemotherapy. This approach is limited, however, by a relatively high risk of transplant-related complications, particularly graft rejection, GVHD, and interstitial pneumonitis. Autologous bone marrow transplantation avoids the problems of graft rejection and GVHD. It does, however, introduce a risk of reinfusing residual leukemia cells with the autologous bone marrow and absence of a possible graft-versus-leukemia effect associated with allogeneic transplants. Bone marrow transplantation is useful in AML. Syngeneic or allogeneic HLA-identical bone marrow transplantation is the preferred treatment for patients under age 45 to 50 who fail chemotherapy. Transplantation is also likely to be superior or comparable to chemotherapy for patients less than 20 to 30 years of age in first remission. Transplantation in older individuals in first remission is controversial; results are comparable to those achieved with postremission chemotherapy. Transplants from donors other than HLA-identical siblings must be considered investigational but may be a reasonable alternative in young individuals in first relapse or second remission. Autotransplants are difficult to evaluate critically but may be considered as investigational therapy for individuals in second or later remission for whom a suitable allogeneic donor is unavailable. Autotransplants in first remission should be restricted to controlled clinical trials because it is otherwise impossible to determine their efficacy. It is uncertain whether ex vivo treatment of the bone marrow to remove leukemia cells is necessary in the context of autotransplantation; again, controlled trials are required. Bone marrow transplantation from an HLA-identical sibling is effective in individuals with ALL who relapse despite chemotherapy. Patients undergoing transplantation while in second or later remission or in relapse have a survival rate superior to those treated with chemotherapy. One important and unresolved issue is whether patients with high-risk ALL should receive bone marrow transplants or intensive postremission chemotherapy while in first remission; controlled clinical trials are needed. Bone marrow transplants from donors other than HLA-identical siblings and autologous bone marrow transplants are investigational approaches that should be considered in selected young patients who fail despite chemotherapy.(ABSTRACT TRUNCATED AT 400 WORDS)     

Role of allogeneic and autologous hematopoietic stem cell transplantation in acute myeloid leukemia

Most younger patients with acute myeloid leukemia will enter remission of disease. Prevention of relapse is now the central therapeutic issue. A number of factors predict the risk of relapse, the most powerful of which is cytogenetics. Both allogeneic and autologous transplantation have been extensively used as remission consolidation, but intensive chemotherapy has also provided improved results such that the choice of consolidation treatment is not clear. Recent prospective trials of allogeneic and autologous transplantation with careful analysis have not always shown a survival benefit, although both approaches have significantly reduced relapse risk. In analysis where relapse risk is taken into account based on cytogenetics, there is little evidence of the benefit of transplantation in good-risk patients, partly because patients in this group who relapse can then undergo successful salvage therapy. The results are still uncertain in standard-risk patients, so transplantation should continue to be used in the context of a trial. Poor-risk patients have a higher failure rate after transplantation, and for these patients novel approaches are required.     

Stem cell transplantation in acute myelogenous leukemia in first remission: what are the options?

Most newly diagnosed patients with acute myeloid leukemia (AML) in first remission will relapse without additional consolidation therapy. The options for consolidation therapy include repeated cycles of high-dose cytosine arabinoside-based chemotherapy and autologous or allogeneic stem cell transplantation (SCT). Chemotherapy alone is associated with the highest risk of relapse, but it has the lowest treatment-related mortality (TRM). Allogeneic SCT has the lowest risk of relapse with the highest TRM, whereas autologous SCT has an intermediate risk of relapse and TRM. Cytogenetic status of patients with AML is the single most important prognostic factor. However, it is increasingly recognized that this factor alone is inadequate for risk stratification. Based on cytogenetic stratification, a good-risk group of patients in first complete remission (CR1) would benefit most from high-dose consolidation chemotherapy. The risks of a SCT outweigh the benefit in this group. In the unfavorable-risk group, an allogeneic sibling SCT in CR1 would be acceptable, whereas the outcomes with chemotherapy alone or with an autologous SCT are dismal. Based on minimal data, a matched-unrelated donor SCT for this group of patients should be recommended. In the intermediate-risk group, strategies are evolving and the use of additional prognosticators will help in decision making. Autologous or allogeneic sibling SCT is a reasonable option in a subset of patients within this group at a high risk of relapse. There are insufficient data to recommend a haploidentical or cord blood transplant for patients with AML in CR1.     

Risks and benefits in a personalized application of allogeneic transplantation in patients with AML in first CR

Allogeneic hematopoietic stem cell transplantation (alloHSCT) strongly reduces relapse in patients with acute myeloid leukemia (AML) in first complete remission (CR). Estimated as relative risk, the graft-vs-leukemia effect of alloHSCT is associated with a hazard ratio of approximately 0.35 with endpoint relapse compared with autologous HSCT or postremission chemotherapy in comparative studies. Strikingly, that hazard ratio is similarly operational in favorable and adverse-risk AML. It suggests that only in case of excessive nonrelapse mortality (NRM) alloHSCT should be withheld as postremission treatment. Therefore, the application of alloHSCT in patients with AML in first CR should be personalized and based on both risks and benefits of alloHSCT, which are on the one hand the risk for NRM and on the other hand the risk of relapse. The risk of NRM can be estimated by a dedicated score for patients with AML in first CR, whereas the latest European LeukemiaNET risk classification may be applied for estimating the risk of relapse. In addition, the assessment of measurable residual disease further discriminates patients with a low vs high risk of relapse and may be incorporated in decision making.     

Are matched unrelated donor transplants justified for AML in CR1?

There has been controversy about the optimal consolidation therapy for patients with acute myeloid leukemia (AML) in first remission. Hematopoietic stem cell transplantation from human leukocyte antigen (HLA)-identical siblings has improved the survival of patients with unfavorable cytogenetics, but has not improved the survival of intermediate- or favorable-risk patients. If an HLA-identical sibling donor is not available, alternative sources of stem cells may be sought. HLA mismatched transplants are associated with an increased risk of graft rejection and graft-versus-host disease, and lower survival. Since large registries of HLA-typed volunteer donors have been established and the newer and more sensitive tissue typing technology can more clearly differentiate between matched and unmatched donors, some AML patients without an HLA-matched sibling have received transplants from an HLA-matched unrelated donor while in first remission. Data from the Center for International Blood and Marrow Transplant Research indicate that survival of patients with unfavorable cytogenetics appears at least as good with unrelated donor grafts as previously reported for matched sibling grafts, and better than consolidation chemotherapy. AML patients in first remission with unfavorable cytogenetics without a matched family donor should be offered an unrelated donor transplant.     

Hematopoietic cell transplantation from unrelated donors for treatment of patients with acute myeloid leukemia in first complete remission

Hematopoietic cell transplantation from a histocompatible sibling is generally recommended for patients with acute myeloid leukemia in first remission with intermediate or high risk disease. Two-thirds of patients lack a matched sibling raising the question of the utility of matched unrelated transplantation for such patients. Retrospective studies from single institutions and registry data report 44-50% disease-free survival at 5-years following ablative unrelated donor transplantation for adults. The German AML 01/99 is the only prospective study evaluating the utility of matched related and unrelated transplantation for AML patients in first remission with high risk disease and reported 4-year survival of 68% with matched related transplants, 56% with matched unrelated transplants and 23% with autografting. Thus, results suggest that for patients with AML in first remission with high risk features (as determined by cytogenetics or >5% blasts on day 15 of induction) who lack matched siblings, unrelated donor transplantation should be considered. Current challenges are to improve our ability to identify those patients most likely to benefit from early transplantation, to better select donors, and to develop transplant preparative regimens that are safer and more effective.     

Thiotepa, busulfan, and cyclophosphamide as a preparative regimen for allogeneic transplantation for advanced myelodysplastic syndrome and acute myelogenous leukemia.

Sixty-two adults underwent marrow or blood stem cell transplantation from an HLA-matched related donor using high-dose thiotepa, busulfan, and cyclophosphamide (TBC) as the preparative regimen for treatment of advanced myelodysplastic syndrome (MDS) (refractory anemia with excess blasts with or without transformation) or acute myelogenous leukemia (AML) past first remission. All evaluable patients engrafted and had complete donor chimerism. A grade 3-4 regimen-related toxicity occurred in eight (13%) patients, and a diagnosis of MDS was the only independent risk factor for grade 3-4 regimen-related toxicity (hazard ratio 9.25, P = 0.01). Day-100 treatment-related mortality (TRM) was 19%. Poor-prognosis cytogenetics increased the risk of day-100 TRM (hazard ratio 11.4, P = 0.003), and use of tacrolimus for graft-versus-host disease prophylaxis reduced the risk of day-100 TRM (hazard ratio 0.13, P = 0.027). For all patients, the three-year relapse rate was 43% (95% CI, 28%-58%). Refractoriness to conventional induction chemotherapy prior to transplantation was an independent risk factor for relapse (hazard ratio 10.8, P = 0.02). Three-year survival was 26% (95% CI, 14%-37%); survival rates were 29% for those transplanted for AML in second remission, 31% transplanted for AML in relapse, and 17% with MDS, and there were no independent risk factors for survival. TBC is an active preparative regimen for advanced AML. Patients with advanced MDS appeared to have a higher risk of toxicity and early mortality, and alternative preparative regimens should be considered for these patients.     

Timed sequential induction chemotherapy and risk-adapted postremission therapy for acute myelogenous leukemia

Cytogenetic analysis at the time of diagnosis predicts outcome in patients with acute myelogenous leukemia (AML). For those patients with favorable risk cytogenetics, stem cell transplant can be delayed until the time of relapse. For those patients with nonfavorable cytogenetic risk profiles, stem cell transplant may be required for optimal survival benefit. We treated patients with de novo AML and age less than 60 years first with etoposide, mitoxantrone, cytarabine, and G-CSF (EMA-G) to induce remission. Patients in complete remission were assigned to treatment with chemotherapy alone if they had favorable risk cytogenetics defined as the identification of a core-binding factor translocation. Patients with any other cytogenetic profile were assigned to treatment with either autologous or allogeneic stem cell transplant depending on the availability of an HLA-matched donor. Following EMA-G, 33 of 40 patients (83%) achieved CR. Of the 25 patients who actually were treated with postremission chemotherapy, 21 were treated with their assigned risk-adapted therapy. Of the 33 patients in remission, 5 year relapse-free survival (RFS) and overall survival (OS) was 46 and 38%, respectively. Our intensive and risk-adapted, stem cell transplant approach to the treatment of patients with AML requires a better definition of risk and does not appear to substantially improve results compared with more standard approaches.     

Assessing the efficacy of allogeneic hematopoietic stem cells transplantation (allo‐HSCT) by analyzing survival end points in defined groups of acute myeloid leukemia patients: A retrospective,multicenter Polish Adult Leukemia Group study

The importance of allogeneic hematopoietic stem cell transplantation (allo‐HSCT) for survival outcomes in patients with acute myeloid leukemia (AML) currently remains unclear. The study aimed to compare measures of clinical treatment for patients with AML in CR1 (the first complete remission) with or without being subjected to allo‐HSCT. These consisted of leukemia‐free survival (LFS), overall survival (OS), cumulative incidence of relapse (CIR), and non‐relapse mortality disease (NRM). Subjects were 622 patients, median age of 44, forming part of the prospective, randomized, and multicenter clinical Polish Adult Leukemia Group trials during 1999–2008. The Mantel–Byar approach was used to assess allo‐HSCT on survival endpoints, accounting for a changing transplant status. Undergoing allo‐HSCT significantly improved the LFS and OS for the entire group of patients with AML in CR1, along with the DAC induction subgroup and for the group with unfavorable cytogenetics aged 41–60. The CIR demonstrated that allo‐HSCT reduced the risk of relapse for patients with AML in CR1 and those with an unfavorable cytogenetic risk. In addition, the NRM analysis showed that allo‐HSCT significantly reduced the risk of death unrelated to relapse for the entire group of AML patients in CR1 and aged 41–60. The allo‐HSCT treatment particularly benefitted survival for the AML in CR1 group having an unfavorable cytogenetic prognosis. Am. J. Hematol. 90:904–909, 2015. © 2015 Wiley Periodicals, Inc.     

Economic impact of genomic diagnostics for intermediate‐risk acute myeloid leukaemia

Acute Myeloid Leukaemia (AML) is a rare but serious group of diseases that require critical decision‐making for curative treatment. Over the past decade, scientific discovery has revealed dozens of prognostic gene mutations for AML while sequencing costs have plummeted. In this study, we compared the cost‐effectiveness of multigene integrative analysis (genomic analysis) with the standard molecular testing currently used for diagnosis of intermediate‐risk AML. We used a decision analytic model with data for costs and outcomes from British Columbia, Canada, to assess the long‐term (10‐year) economic impacts. Our results suggest that genomic analysis would result in a 26% increase in the use of first‐remission allogeneic stem cell transplantation. The resulting treatment decisions and downstream effects would come at an additional cost of $12 556 [2013 Canadian dollars (CAD)] per person and the incremental cost‐effectiveness ratio would be $49 493 per quality‐adjusted life‐year gained. Cost‐effectiveness was dependent on quality of life during the long‐term (5–10) years of survival, relapse rates following first‐remission chemotherapy and the upfront cost of transplantation. Non‐relapse mortality rates, short‐term quality of life and the cost of genomic sequencing had only minor impacts. Further research on post‐remission outcomes can lead to improvements in the cost‐effectiveness of curative treatments for AML.     

Allogeneic haematopoietic cell transplantation for adult acute myeloid leukaemia in second remission: a retrospective study of the Adult Acute Myeloid Leukaemia Working Group of the Japan Society for Haematopoietic Cell Transplantation (JSHCT)

To evaluate the outcomes and prognostic factors following allogeneic haematopoietic cell transplantation (HCT) for adult acute myeloid leukaemia (AML) in second complete remission (CR2), we retrospectively analysed the Japanese registration data of 1080 adult AML patients in CR2 who had received allogeneic HCT. The probability of overall survival and the cumulative incidence of relapse at 3 years was 66% and 19%, respectively. In multivariate analysis, older age, poor cytogenetics and shorter duration of first complete remission were significantly associated with a higher overall mortality. Our data demonstrated the significant efficacy of allogeneic HCT for adult AML in CR2.     

A simple, robust, validated and highly predictive index for the determination of risk-directed therapy in acute myeloid leukaemia derived from the MRC AML 10 trial

Data on 1711 patients, aged up to 55 years, in the MRC AML 10 trial were used to create a prognostic index for use in risk-directed therapy decision making for younger patients with acute myeloid leukaemia (AML). Two parameters, response after course 1 and cytogenetics, were strongly predictive of outcome. For patients with complete remission, partial remission and resistant disease, 5-year survival from the start of course 2 was 53%, 44% and 22% and relapse rates were 46%, 48% and 69% respectively, and for patients with favourable, intermediate and adverse karyotypic abnormalities, survival was 72%, 43% and 17% and relapse rates were 34%, 51% and 75% respectively (all P < 0.0001). Patients with FAB type M3 but no cytogenetic t(15;17) also had a low relapse rate (29%). These three factors were combined to give three risk groups: good (favourable karyotype or M3, irrespective of response status or presence of additional abnormalities), standard (neither good nor poor), poor (adverse karyotype or resistant disease, and no good-risk features). Survival for these three groups was 70%, 48% and 15% respectively and relapse rates were 33%. 50% and 78% (both P < 0.0001). The index is simple (based on just three parameters), robust (derived from 1711 patients), highly discriminatory (55% survival difference between good and poor risk) and validated, so can be applied in the clinical setting to assist with therapeutic decisions as in the current AML 12 trial.     

Prognosis of patients with core binding factor acute myeloid leukemia after first relapse

Core binding factor acute myeloid leukemia is known to have a favorable prognosis, however, there have been no detailed analyses on prognostic factors after first relapse. Using a nationwide database, we retrospectively analyzed core binding factor acute myeloid leukemia patients who relapsed after being treated with chemotherapy alone during their first complete remission. Of a total of 397 patients who were diagnosed with core binding factor acute myeloid leukemia, 208 experienced a first relapse, and analyses were performed in 139 patients for whom additional data were available. In the entire cohort, the overall survival rate after relapse was 48% at 3 years. By multivariate analysis, younger age at diagnosis, a longer interval before relapse, and inv(16) were shown to be independently associated with better survival after relapse. Although there was no significant difference in survival after relapse between patients who underwent allogeneic hematopoietic cell transplantation and those who did not in the overall series of relapsed patients, we found that transplantation significantly improved survival among patients who had t(8;21) (54% versus 26% at 3 years, P=0.002). In addition, among patients with t(8;21), those who had different cytogenetics at relapse had a significantly improved survival after transplantation, while those who had same cytogenetics did not. We showed that the prognosis differs significantly and optimal treatment strategies may vary between groups of patients with core binding factor acute myeloid leukemia with different cytogenetic profiles at relapse. These findings may help to guide therapeutic decisions after first relapse.     

Long-term follow-up of relapsed childhood acute lymphoblastic leukaemia

We have reviewed the outcome after relapse in a cohort of 505 children with acute lymphoblastic leukaemia (ALL) seen at a single institution. The majority of relapses (74%) occurred within 3 years from diagnosis, and most involved the bone marrow alone or with overt extramedullary relapse. Early relapse was more common in children with T-ALL and those with unfavourable cytogenetics. Factors influencing second remission included length of first remission and type of relapse. Children who had not received previous cranial irradiation had a superior survival. The German relapse score involving length of first remission, site of relapse and immunophenotype was highly predictive of outcome: event-free survival with 95% confidence intervals at 6 years for patients who received modern treatment [intensive chemotherapy or bone marrow transplantation (BMT)] was 78% (51-92%) for standard risk, 41% (33-49%) for intermediate risk and 19% (10-31%) for highest risk. Retrospective comparison of BMT with chemotherapy showed no difference in the intermediate-risk group but a possible advantage in the highest risk group. Follow-up of 235 patients who relapsed after chemotherapy and received a third course of treatment showed an extremely high early attrition rate, but a small number of patients survived in third remission. We conclude that new approaches are needed to individualize therapy in intermediate-risk patients and to improve the outcome for those in the highest risk group. Only a small number of children can be treated effectively in third remission.     

Progress in the treatment of acute myeloid leukaemia in adults

There has been important progress in the treatment of Acute Myeloid Leukaemia (AML) in patients under 60 years. A remission rate of 80% can be achieved by several schedules, and 40-45% of patients diagnosed will survive. It may still be possible to improve remission induction treatment eg by intensifying the Ara-C dose although may this only be detectable in an improved disease free survival. The is to reduce relapse. The risk main challenge is pre-determined by a number of powerful risk factors. In the experience of the MRC age, cytogenetics and clearance of blasts from the bone marrow after course 1. Using the later two in combination good risk patients (FAB M3, t(8;21) t(15;17) inv(16)) have a relapse risk of 32%. Poor risk (blasts >15% after course 1 or abnormalities of Chs 5 or 7, 3q- and complex changes have a relapse risk of 82%. All other cases are standard risk and ve a relapse risk of 56%. FLT3 mutations have been detected in about 25% of cases and provide additional negative predictive value overall and within each risk group. The assessment of the most effective consolidation treatment must be made taking into account the heterogeneity of the relapse risk. The MRC investigated the role of allo and autoBMT in addition to intensive chemotherapy. The data was analysis on an intent-to-treat or donor vs no donor basis. Although both types of transplant were able to reduce relapse overall and in all risk groups, there was an overall survival advantage only in standard risk patients. Since chemotherapy has improved since this study, there remains uncertainty about the benefit of transplant in all risk groups. Overall this experience has demonstrated that relapse can be reduced with more therapy. It is probable that the limits of conventional chemotherapy have been reached. The new AML15 trial will assess the value of adding the immunoconjugate (Mylotarg) to induction and/or chemotherapy. Improvements in older patients have been less detectable. MRC trials over the last 20 years show an improvement in remission rate (now 65%) but persistent poor survival (12% at 5 years). In the MRC AML11 Trial three induction schedules were compared (DAT vs ADE vs MAC) with DAT being superior. A comparison of a total of 3 vs 6 courses of treatment or the addition of interferon maintenance did not improve results. Newer approaches currently being assessed include resistance modulation; addition of immunoconjugate and minigrafts. New targets for treatment are emerging of which the most interesting is FLT3 inhibitors.     

Should we T cell deplete sibling grafts for acute myeloid leukaemia in first remission?

There is controversy regarding the best approach to the management of patients with acute myeloid leukaemia (AML) in first remission (CR1). The impact of matched related allogeneic transplant in CR1 on the overall survival is equivocal, but what is not in doubt is a significant reduction in the relapse risk, compared to both autologous transplants and intensive chemotherapy, which is because of the allogeneic or the graft-versus-leukaemia (GVL) effect. Yet, this does not always translate to improved survival. T cell depletion (TCD) can reduce deaths related to graft-versus-host disease (GVHD) and its therapy, but might increase the relapse risk. The existing literature suggests that TCD is associated with a disease-free survival (DFS) of 53-80% and is associated with a lower relapse risk than anticipated (0-30%). We discuss the evolution of TCD in allogeneic transplantation and its relevance in AML-CR1 with regard to GVHD, DFS, immune reconstitution and GVL effect. It is possible that by reducing TRM related to GVHD and extramedullary toxicities, particularly in the older patients, TCD might improve the impact of allogeneic transplantation in AML-CR1, provided the immune reconstitution and the relapse risk are not adversely affected. Randomised studies are underway to address these issues.     

Maintenance therapy in acute myeloid leukemia: What is the future?

Relapse remains the primary obstacle to long-term survival in patients with acute myeloid leukemia (AML) who achieve a remission following standard induction and consolidation therapy. Although allogeneic hematopoietic stem cell transplantation decreases the risk of relapse for many patients, relapse is common even among these patients. A number of approaches to maintenance therapy for AML have been studied with the goal of finding an agent with a tolerable side effect profile that may be given to patients in remission, typically for a prolonged period of time, in order to decrease the risk of relapse. Numerous trials that evaluated cytotoxic agents as maintenance therapy did not find any improvement in survival, but more recent studies of alternative approaches to maintenance including immunomodulation, epigenetic reprogramming, and targeted agents have been much more promising. In this article, we review the current evidence for various maintenance strategies for AML including immunotherapy, hypomethylating agents, and targeted therapies, particularly FLT3 inhibitors. We also discuss promising emerging approaches to maintenance for AML, including the incorporation of measurable residual disease assessment.     

Prophylactic donor lymphocyte infusion after allogeneic stem cell transplantation in acute leukaemia – a matched pair analysis by the Acute Leukaemia Working Party of EBMT

Strategies for relapse prevention after allogeneic transplantation in acute leukaemia are warranted. A registry-based matched-pair analysis evaluated the efficacy of prophylactic donor lymphocyte infusion (proDLI). Adults receiving proDLI in complete remission (CR) and controls were pair-matched for age, diagnosis, cytogenetics, stage, donor, gender, conditioning and T-cell depletion. Eighty-nine pairs were identified (median follow-up: 6.9 years). Within the entire cohort, no difference was observed. However, among patients with high-risk acute myeloid leukaemia (AML) (unfavourable cytogenetics and/or transplanted beyond first CR), proDLI recipients had improved overall survival (69.8% vs. 40.2% in controls, P = 0.027). ProDLI has moderate efficacy, but can contribute to improved outcome in high-risk AML.     

Allogeneic marrow transplantation for acute nonlymphoblastic leukemia after first relapse

Sixty-two patients with acute nonlymphoblastic leukemia in first relapse or second remission were treated with allogeneic marrow transplantation from HLA-matched siblings. In 17 patients (group 1), no attempt at reinduction of remission was made prior to transplantation. In 20 patients (group 2), attempts at inducing a second remission prior to transplantation were unsuccessful; and in 25 patients (group 3), a second remission was achieved. Five of 17 patients (29%) in group 1, 2 of 20 (10%) in group 2, and 5 of 25 (20%) in group 3 are surviving disease-free 2-6 yr after grafting. Early mortality from nonleukemic causes was equal in the 3 groups, but the risk of recurrent leukemia after transplantation was less in patients transplanted without attempts at reinduction (group 1). Among patients transplanted in relapse, those in early relapse (less than 30% blast cells in the marrow) appeared to do better than patients in florid relapse. The results obtained in group 1 are as good as or better than those achieved in patients transplanted in second or subsequent remission. Thus, for patients with acute nonlymphoblastic leukemia not transplanted in first remission, the optimal time for transplantation would appear to be as soon as possible after the first relapse.