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Stem Cells, Vol. 14, No. 1, 69-78, January 1996
© 1996 AlphaMed Press

CONCISE REVIEW

Autologous Bone Marrow Transplantation for Acute Myeloid Leukemia

Kevin Imriea, Karel A. Dickeb, Armand Keatinga

a The University of Toronto Autologous Blood and Marrow Transplant Program, The University of Toronto, Toronto, Ontario, Canada;
b Arlington Cancer Center, Arlington, Texas, USA

Key Words. Bone marrow transplantation • Acute myeloid leukemia • Chemotherapy • Purging • Bone marrow • Blood cells

Dr. A. Keating, The Toronto Hospital, General Division, Mulock-Larkin Wing 2-036, Toronto, ONT, Canada, M5G 2C4.


   Abstract
Top
 Abstract
Introduction
 ABMT, alloBMT and Conventional...
 Timing of ABMT
 Contamination of the Autograft
 Blood Cell Autotransplants
 High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
 Conclusions
 References
 
Despite progress over the past three decades, most patients with acute myeloid leukemia (AML) treated with conventional chemotherapy alone relapse and die of recurrent leukemia. Treatments used to improve outcome include allogeneic (alloBMT) and autologous bone marrow transplantation (ABMT). Indications for transplantation and the relative merits of alloBMT and ABMT remain unclear. In this review, we evaluate evidence supporting a role of ABMT in AML and compare the results with outcomes after alloBMT. In addition, we discuss areas of controversy including the optimal timing for ABMT, the role of bone marrow purging, the place of peripheral blood stem cell collection, the high dose regimen, and post-transplant immunotherapy to reduce relapse.


   Introduction
Top
 Abstract
 Introduction
ABMT, alloBMT and Conventional...
 Timing of ABMT
 Contamination of the Autograft
 Blood Cell Autotransplants
 High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
 Conclusions
 References
 
Changes in conventional chemotherapy over the past three decades have led to modest improvements in the rate and duration of remission for patients with acute myeloid leukemia (AML) [1,2]. The majority of patients who achieve remission, however, will relapse within 12-24 months, and 7%-34% of patients will be alive and disease-free five years after diagnosis [3]. Post-remission therapy with conventional dose chemotherapy either as consolidation or maintenance prolongs remission duration but does not significantly increase the proportion of long-term survivors [4,5]. In vitro, leukemic cells exposed to chemotherapy demonstrate a steep dose-response relationship [6–8] and, in vivo, even in the conventional dose range, escalation of the intensity of chemotherapy can improve outcome [9,10]. For this reason, intensification with high-dose chemoradiotherapy with hematopoietic cell infusion is an attractive treatment strategy.

HLA-identical related allogeneic bone marrow transplantation (alloBMT) provides a means of hematopoietic reconstitution from a graft that is leukemia-free after the administration of supralethal doses of chemotherapy and radiotherapy [11]. Long-term disease-free survival (DFS) rates of over 50% are regularly reported from single institution and registry studies suggesting a potential role for this modality in post-remission therapy [12]. Only a minority of patients with AML, however, will be eligible for alloBMT because of age restrictions as well as lack of an HLA-identical sibling [13].

Autologous bone marrow transplantation (ABMT) is used increasingly in the management of hematologic malignancies and a number of solid tumors [14]. As ABMT can be performed in patients in remission up to 60 years of age or more without the need for a matched donor, it is available to increased numbers of patients not meeting the requirements for alloBMT [15]. The first reports of ABMT in the management of AML were published in the late 1970s [16,17], and since then the number of autografts performed for this indication has markedly increased. A decade later, it was estimated that over 700 patients undergo ABMT annually worldwide for leukemia, representing over 10% of all autotransplants [18]. Over 250 patients are reported to the Autologous Blood and Marrow Transplant Registry—North America (ABMTR) annually [19].

In this report we review ongoing clinical trials of ABMT for AML, areas of controversy and future directions for therapy.


   ABMT, alloBMT and Conventional Therapy
Top
 Abstract
 Introduction
 ABMT, alloBMT and Conventional...
Timing of ABMT
 Contamination of the Autograft
 Blood Cell Autotransplants
 High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
 Conclusions
 References
 
Three treatment options are available to the young patient with AML in remission after induction therapy: conventional consolidation chemotherapy alone, alloBMT and ABMT. The relative role of these treatments remains the principal controversy in the postremission management of AML. Three levels of evidence are available to answer this question: single arm studies with comparisons with historical controls, prospective randomized trials and registry data.

More than 1,000 patients with AML have been evaluated in single arm trials of ABMT [14]. DFS rates of over 40% are routinely reported for patients undergoing transplantation in first complete remission (CR1) [20–26]. These results appear substantially better than those reported for patients treated with conventional chemotherapy alone. Unfortunately the data are difficult to interpret because trials involving ABMT often include a highly selected group of patients [27]. For example, patients over the age of 60 years are often excluded as are those with secondary AML. Thus, subjects with the two worst prognostic features are excluded from most series [27,28]. In addition, patients who receive ABMT must have achieved a CR and remained in remission for a sufficient period to allow for harvesting of hematopoietic cells and autografting. In trials of conventional treatment, patient- and/or disease-related exclusion criteria may also be applied, occasionally not very explicitly, and these add to the difficulty in making comparisons with ABMT outcomes [27]. Controlled prospective randomized trials may overcome many of these limitations.

Complete results have been reported in two of at least six randomized trials comparing ABMT with consolidation chemotherapy and alloBMT. Preliminary results have been presented from four other trials (Table 1Go). The BGM 84 trial evaluated 85 patients under the age of 60 with AML in first remission [29]. All received standard induction therapy and conventional consolidation. Patients with a related HLA-identical donor were offered alloBMT, and those without were randomized to receive either a double autologous bone marrow transplant or four monthly cycles of chemotherapy. Twenty received an alloBMT, and 32 were randomized. DFS was significantly longer in the transplant arms than in the conventionally treated group. Actuarial three-year DFS was 66% for alloBMT, 41% for ABMT and 16% for chemotherapy alone (p < 0.0002). Results with alloBMT and ABMT were not statistically different. The small number of patients in this trial limits the power of the analysis.


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  		Table 1. Summary of randomized trials
 
The EORTC-GIMEMA trial used a similar design to evaluate 990 patients with AML in CR1 [30]. Patients with an HLA-identical sibling received an allogeneic transplant, while those without a donor were randomized to receive either a single autologous transplant with unpurged bone marrow or conventional consolidation. Intensive therapy consisted of either cyclophosphamide and TBI or busulfan and cyclophosphamide. One hundred and sixty-eight patients were eligible for alloBMT, and 254 were randomized (128 to ABMT and 126 to conventional consolidation). DFS was significantly higher in patients undergoing alloBMT or ABMT versus conventional consolidation (54% and 48% versus 30%; p = 0.05), but overall survival was not significantly different at a median follow-up of 3.3 years (59%, 56% and 46%, respectively). The authors suggested that survival in the group randomized to conventional chemotherapy was high due to high salvage rates after relapse (62%) in this arm. It should be noted that 24 of the 58 patients relapsing in this group subsequently underwent transplantation (2 alloBMT, 22 ABMT). This study suggests that ABMT may be equivalent to alloBMT and superior to conventional chemotherapy in the management of the younger patient with AML in CR1.

This trial is the only large randomized comparison of ABMT, alloBMT and conventional chemotherapy published in other than abstract form. In general, it is well-designed, and the data are not overinterpreted. Some criticisms of the study have been offered [31]. The first is that the patient population is highly selected and has a very young median age. Most centers restricted enrollment to subjects under 45 years. Another difficulty in interpreting the results is the relatively low proportion of patients assigned to transplantation who completed the assigned therapy. Of particular concern is the relatively large number of patients who did not receive ABMT due to refusal by the patient or treating physician.

The MRC AML-10 trial was designed to evaluate two different conventional induction regimens as well as to compare ABMT, alloBMT and aggressive consolidation chemotherapy [32]. In the first phase of the trial, newly diagnosed patients were randomized to receive one of two conventional induction regimens, ADE or DAT. Patients who achieved a CR with either regimen then received two courses of consolidation chemotherapy; those with HLA-compatible siblings obtained an alloBMT, and the remainder were randomized to receive either ABMT, using cyclophosphamide and TBI followed by infusion of unpurged bone marrow, or no further treatment. Between May 1988 and October 1994, 1,800 patients were enrolled to the initial phase. Evaluation followed an intention-to-treat model. Less than half (766) of the patients achieved remission and were evaluable in the second phase. Of these, 299 had an HLA-compatible related donor and 174 were transplanted. Of the remaining 567 patients, 357 were randomized. Reasons for nonrandomization included relapse prior to randomization (91 patients) and refusal by patients or their treating physicians (365 patients). The median follow-up for all patients was 2.7 years. Five-year survival did not differ among the three arms (58% for alloBMT, 54% for ABMT and 52% for the no further treatment arm). Treatment-related mortality was 19% for alloBMT and 11% for ABMT. Relapse rates at five years were not different among the arms (33% for alloBMT, 43% for ABMT and 54% for no further treatment). This trial has not demonstrated a benefit with either form of bone marrow transplantation in addition to intensive chemotherapy; however, longer follow-up may be required because the overall survival of all evaluable patients was high [33].

A multicenter randomized study comparing these three treatment modalities from the French GOELAM group has also been presented in preliminary form [34]. Four hundred and seventy adults with newly diagnosed AML were enrolled, and 326 who achieved CR were evaluable. Patients under the age of 40 with an HLA-compatible sibling were offered alloBMT, while the remainder were randomized to consolidation chemotherapy or ABMT using busulfan and cyclophosphamide and unpurged bone marrow. Seventy patients had an HLA-identical donor, and 171 were randomized. The four-year survival of all patients was 40%. No significant differences in relapse rate, DFS or survival were detected among the three arms at a median follow-up of 44 months.

Preliminary results of another small randomized trial have been presented by the BGMT group [35]. The study design was similar to the other trials discussed above. Thirty-six patients were allocated to receive alloBMT, and 99 patients were randomized to either intensive chemotherapy or ABMT. Three-year survival was significantly greater for those receiving alloBMT than for others (63% ± 16% versus 37% ± 10%). A comparison of ABMT and intensive chemotherapy was not reported.

These studies differ in design, particularly with respect to upper age limit for inclusion, especially for alloBMT. A further difference is the extent of conventional chemotherapy. The MRC10 trial randomized patients after two courses of consolidation chemotherapy to ABMT or no further treatment, whereas the EORTC-GIMEMA, BGMT and GOELAM trials randomized patients at an earlier point to ABMT or further chemotherapy. This difference is important as, in the MRC10 trial, patients in the ABMT arm were exposed to the toxicity of both the consolidation chemotherapy and the transplant intensive therapy regimen, while the other arm received no further therapy after randomization and thus had no treatment-related mortality. A further problem common to all the trials is the relatively low proportion of eligible patients who actually undergo randomization.

While the first fully published report is favorable towards transplants, preliminary reports of other trials do not indicate an advantage for either allo- or autotransplant over consolidation chemotherapy alone; however, the median follow-up in most of these studies is relatively short. In addition to longer follow-up, a meta-analysis of all completed trials may be helpful in reaching a conclusion.

Bone marrow transplant registries provide an additional source of data to compare alloBMT and ABMT. Preliminary data from the International Bone Marrow Transplant Registry (IBMTR) and the ABMTR comparing the two forms of transplantation were recently presented [36]. The outcome of 607 autotransplants performed between 1989 and 1993 reported to the ABMTR was compared with 998 HLA-identical sibling transplants performed during the same period and reported to the IBMTR. Time from diagnosis to transplant was similar for the two treatments for those undergoing transplantation in CR1, but longer for the ABMT group transplanted in CR2. Two-year relapse rates were significantly higher in patients treated with ABMT (36% ± 6% versus 21% ± 4% in CR1; p = 0.0001) but this effect was offset by a higher treatment-related mortality in the alloBMT cohort (28% ± 4% versus 13% ± 4%; p = 0.0001). The two-year leukemia-free survival rates were not significantly different (55% ± 6% for ABMT versus 58% ± 4% for alloBMT; p = not significant). A similar pattern was evident for patients transplanted in CR2.

In summary, considerable early data are available from randomized trials as well as from reviews of transplant registries to suggest that ABMT is a feasible option for patients with AML. To date, however, no firm evidence exists that either alloBMT or ABMT confers a survival advantage over conventional consolidation chemotherapy. While these data are preliminary and longer follow-up is necessary, over 3,000 patients have been accrued to these randomized trials and 1,200 patients randomized to ABMT versus consolidation chemotherapy. It is therefore likely that we will have sufficient evidence to determine the optimal postremission therapy for the younger patient with AML.


   Timing of ABMT
Top
 Abstract
 Introduction
 ABMT, alloBMT and Conventional...
 Timing of ABMT
Contamination of the Autograft
 Blood Cell Autotransplants
 High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
 Conclusions
 References
 
While ABMT can be performed as consolidation therapy in first or subsequent complete remission or as salvage therapy for patients in relapse, the optimal timing for transplantation has yet to be established. The majority of transplants for AML are performed in CR1. The ABMTR began collecting data on autotransplants in 1989 [37] and has received information on over 1,100 autotransplants for AML from 98 institutions. Fifty-eight percent of these were performed in CR1, 27% in CR2 and 15% in other disease states. The best long-term DFS rates are observed in patients transplanted in CR1: two-year survival rates were 56% for those in CR1, 36% in CR2 and 24% in other states. Single institution studies report similar DFS rates of 35%-76% for CR1 [20–25]. The encouraging results observed in this setting may be due, in part, to inclusion of patients who were cured by conventional chemotherapy alone prior to transplantation. Such patients are exposed to the toxicity of high-dose therapy without its accompanying benefits.

ABMT performed during CR2 or later is associated with a lower likelihood of long-term survival. Single institution studies report DFS rates of 18%-56% [20–21, 37,38]. Results of the European Bone Marrow Transplant (EBMT) group and ABMTR registries show DFS rates of 34% and 36%, respectively [36,37]. A recent study with a high-dose regimen consisting of busulfan and cyclophosphamide followed by infusion of marrow purged with 4-hydroxycyclophosphamide (4-HC) showed a two-year DFS of 56% in CR2, results that are comparable to outcomes in CR1 at most centers. The inferior results generally obtained in CR2 may be attributable to fewer patients already cured by conventional chemotherapy, greater likelihood of autograft contamination by malignant cells for those receiving autografts collected in second rather than first remission, higher incidence of chemotherapy resistance, and poorer patient performance status and general health.

ABMT as a means of salvaging patients in active relapse has generally been unsuccessful [14]. Complete remission rates of 55% to 78% are obtained, particularly when marrow harvested in first CR is used, but long-term survivors are rare [14,41]. Schiffman et al. harvested the marrow of 98 patients with AML in first remission with intent to transplant patients in early first relapse [42]. Thirty-three patients (33%) have not relapsed with a median follow-up of 72 months, 24 patients received chemotherapy with intent to transplant in CR2, and 38 patients were transplanted at the first sign of relapse. In this latter group, relapse-free survival was 41% with seven patients disease-free 12 to 48 months after ABMT.

Although best results are obtained in CR1, optimal timing of transplant in the disease course is unclear. Alternative strategies such as harvesting patients in CR1 for autotransplant in relapse or second remission may prove more effective by saving cured patients from toxic and expensive therapy. Further studies combining autotransplant and chemotherapy databases may help to determine whether the benefits of this approach are offset by losing some patients at first relapse as a result of treatment failure.


   Contamination of the Autograft
Top
 Abstract
 Introduction
 ABMT, alloBMT and Conventional...
 Timing of ABMT
 Contamination of the Autograft
Blood Cell Autotransplants
 High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
 Conclusions
 References
 
The possibility of contamination of the autograft with leukemic cells remains the major theoretical disadvantage of ABMT for AML [14]. Recurrence of leukemia following ABMT can be attributed to two possible sources: persistence of minimal residual disease in the patient despite administration of high-dose therapy or reinfusion of leukemic cells in the autograft [43]. The relative contributions of each to relapse remains controversial and is of paramount importance in guiding changes in treatment strategies. Efforts to decrease malignant contamination of the autograft are unlikely to affect outcome if relapse is principally due to residual leukemia in the patient after high-dose therapy.

It is likely that the bone marrow of most patients with AML early in CR1 is contaminated with at least a small number of leukemic cells, since most patients relapse after conventional chemotherapy alone. Despite this, single institution studies of patients undergoing ABMT with unpurged marrow in CR1 show long-term DFS rates of 35%-56% [24–26,38–40,44,45]. This suggests that the mere presence of leukemic contamination is insufficient for relapse. In animal models, leukemic cells are more sensitive to cryopreservation and thawing than are hematopoietic stem cells, with only 1% surviving the process [46]. The process of cryopreservation may potentially reduce leukemic contamination below a theoretical threshold needed for malignant overgrowth. A mathematical model used to predict the likelihood of developing relapse for a given burden of leukemic cells has been validated in the Brown Norway rat model and extrapolated to humans [43]. This model uses estimation of relative tumor burden in the patient and the autograft to suggest that, for most patients, relapse is due to persistent leukemic cells resistant to the high-dose regimen.

Early studies of hematopoietic cell gene-marking support the role of the autograft in contributing to relapse. Brenner et al. [47] transferred the neomycin-resistance gene into bone marrow cells harvested from children with AML in remission. Two patients relapsed following ABMT with marked cells, and in both cases the blasts contained the neomycin-resistance gene. These data suggest that, in some cases at least, leukemic contamination of the autograft contributes to relapse.

Further controversy over the contribution of the autograft to relapse comes from studies of bone marrow purging. Purging is the process of treating the marrow autograft in vitro in an attempt to decrease or eliminate leukemic contamination. This can be performed using chemotherapeutic agents such as 4-HC or mafosfamide, immunologic techniques, long-term culture, or physical methods [48–56].

DFS rates reported from single-arm studies of ABMT using unpurged marrow for patients in CR1 are similar to those reported in similar series using marrow purged with 4-HC or mafosfamide [5,20,24–26, 29,40,41,44,45,56] and are not inferior to reports of syngeneic BMT in this setting [57]. Furthermore, purging is not without disadvantages. Purging methods are expensive and labor intensive and are associated with a significant delay in engraftment compared with historical controls of unpurged autotransplants as well as increased rates of opportunistic bacterial and viral infections [58].

The place of purging cannot be answered by comparing small single arm studies of purged and unpurged autotransplants. No randomized studies of purging have been performed in AML, but a nonrandomized multicentered EBMT group study of 263 patients suggests a benefit to the purging of marrow with mafosfamide in patients autografted in early CR1 [40]. The two-year relapse rate in this initial analysis was only 20%, lower than most reports of alloBMT. A subsequent analysis of 919 patients from this registry, while demonstrating higher relapse rates, nonetheless continued to show a benefit for purging [53]. Two-year relapse rates were 35% and 47% for patients receiving purged and unpurged marrow, respectively (p = 0.006). The benefit of purging was seen only in those patients autografted within six months of achieving CR who received TBI as part of the intensive therapy regimen. The role of particular purging methods will be determined in large randomized studies. It is possible that the generic question may be more readily answered by analysis of ABMTR and other registry data.


   Blood Cell Autotransplants
Top
 Abstract
 Introduction
 ABMT, alloBMT and Conventional...
 Timing of ABMT
 Contamination of the Autograft
 Blood Cell Autotransplants
High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
 Conclusions
 References
 
Autologous transplants performed with blood cells alone or in combination with bone marrow may be associated with faster hematopoietic recovery than bone marrow alone [59]. In addition, since peripheral blood collected during recovery from chemotherapy may have an increased proportion of normal progenitors [60] the use of blood cell transplantation (BCT) in AML has generated considerable interest [61]. Korbling et al. compared BCT with ABMT using purged marrow in 43 consecutive patients with AML in CR1 [62]. Faster engraftment was seen with BCT, but there was a trend towards lower DFS (35% versus 51%). Unfortunately, the study was closed prematurely. A retrospective analysis of the EBMT working group compared 28 patients undergoing BCT with 683 patients who had undergone ABMT. The ABMT control group included purged and unpurged marrow grafts. Neutrophil recovery was faster in the BCT group with a comparable DFS (39% versus 42% for BCT and ABMT, respectively) [63]. Preliminary results of 135 patients randomized to ABMT versus BCT found no difference in three-year DFS (48% and 41% for ABMT and peripheral blood stem cell transplant, respectively) but again showed accelerated neutrophil recovery with BCT [64]. BCT in AML appears to be comparable to ABMT in DFS and is associated with more rapid engraftment. Final results of randomized trials will be needed to allay fears of higher relapse rates with BCT raised by earlier nonrandomized studies.


   High-Dose Therapy Regimens
Top
 Abstract
 Introduction
 ABMT, alloBMT and Conventional...
 Timing of ABMT
 Contamination of the Autograft
 Blood Cell Autotransplants
 High-Dose Therapy Regimens
Prevention of Relapse Post-ABMT
 Conclusions
 References
 
In alloBMT, the high-dose regimen serves three distinct purposes: cytoreduction, immunosuppression and, theoretically, the creation of space to allow engraftment [65], whereas, in ABMT, the high-dose regimen serves principally to eradicate the malignant cells [66]. While in alloBMT there are limited data to indicate that the high-dose regimen used influences relapse rates [67,69], no studies in ABMT directly address this issue.

Results of single institution trials are difficult to compare because of differences in inclusion criteria as well as differences in purging. DFS rates range from 35% with cyclophosphamide and TBI [23] to 78% with busulfan and etoposide [20]. These outcomes are likely to fall within the 95% confidence intervals of most small trials. Alkylating agents with or without TBI are the cornerstone of most regimens because of their steep dose-response curves in leukemia [6,8]. High-dose etoposide has elicited interest as it has synergistic activity with alkylating agents in some systems; moreover two recent studies that include the agent in regimens for patients transplanted in CR1 found high DFS rates [20,45,69].

Demonstration of the superiority of one regimen over another requires prospective randomized trials or comprehensive evaluation of registry data. It is likely, however, that the high-dose regimen will not be the major determinant of outcome [70].


   Prevention of Relapse Post-ABMT
Top
 Abstract
 Introduction
 ABMT, alloBMT and Conventional...
 Timing of ABMT
 Contamination of the Autograft
 Blood Cell Autotransplants
 High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
Conclusions
 References
 
Relapse rates for good prognosis patients undergoing ABMT in CR1 exceed 20% even in the most favorable series [20], and most centers report higher rates. In CR2, relapse after ABMT is more frequent. Results may be improved with better patient selection and newer high-dose therapy regimens and possibly by marrow purging, but strategies to eliminate minimal residual disease after transplantation may hold the greatest promise.

In alloBMT, graft versus leukemia (GVL) is known to reduce relapse rates following transplantation [70]. Patients with leukemia who develop graft-versus-host disease (GVHD) following alloBMT have lower relapse rates [71], and patients who relapse following alloBMT for chronic myeloid leukemia may enter remission after GVHD is induced by reduction of immunosuppression or infusion of donor leukocytes [72]. These observations provide a rationale to induce GVHD following ABMT [73]. Cyclosporin can induce GVHD in rodent models as well as in some patients undergoing ABMT [74,75]. Mild to moderate cutaneous GVHD has been induced after ABMT for AML, but the clinical significance of this must await results of large prospective studies [76].

Another strategy under investigation is modulation of natural killer (NK) and lymphocyte function to eliminate minimal residual disease following transplant. Interleukin 2 (IL-2) enhances the cytotoxicity of lymphocytes and NK cells and has been administered with or without autologous lymphocyte-activated killer (LAK) cells [77,78]. Early results of single arm studies show some promise; however, toxicity appears to be high, particularly when LAK cells are administered [78]. IL-1ß also modulates immune effector cell function and has been evaluated as immunotherapy post-ABMT for AML [79]. In a Phase I study, IL-1ß was administered i.v. for five days to 17 patients with AML beginning on the day of marrow infusion. Survival was improved compared with 74 historical controls, although toxicity was greater.

Roquinimex (linomide), an oral quinoline derivative, has modulatory effects on T cell, NK cell and monocyte function. Unlike IL-1ß and IL-2, it appears to be well-tolerated and relatively nontoxic. Two Phase III randomized trials evaluating the effect of Roquinimex post-ABMT for AML are underway [80].


   Conclusions
Top
 Abstract
 Introduction
 ABMT, alloBMT and Conventional...
 Timing of ABMT
 Contamination of the Autograft
 Blood Cell Autotransplants
 High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
 Conclusions
References
 
ABMT shows promise in the postremission management of patients with AML. The optimal role of this treatment has not yet been established. Results of large randomized trials currently underway are likely to provide an answer to this question. The value of bone marrow purging remains controversial and will only be settled by comprehensive reviews of registry data or large prospective randomized trials. Further evidence may be obtained from gene marking experiments analyzing the effect of different purging agents on recurrence. Refinements such as the use of blood cells, development of new high-dose regimens, and post-transplant immunotherapy may decrease toxicity associated with the procedure and reduce treatment failure.


   References
Top
 Abstract
 Introduction
 ABMT, alloBMT and Conventional...
 Timing of ABMT
 Contamination of the Autograft
 Blood Cell Autotransplants
 High-Dose Therapy Regimens
 Prevention of Relapse Post-ABMT
 Conclusions
 References
 

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Received May 26, 1995; accepted for publication May 26, 1995.



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