Autologous bone marrow transplantation for high risk acute lymphoblastic leukemia: clinical relevance of ex vivo bone marrow purging with monoclonal antibodies and complement.

Herein we describe our experience with 75 consecutive autologous BM transplants for patients with high-risk ALL, with special attention to the clinical impact of BM purging. Fifty-two patients received purged BM using monoclonal antibody (MoAb) cocktails and complement, and 23 patients received untreated BM. The distribution of prognostic factors was similar in both groups. Hemopoietic reconstitution was adequate and did not differ in the two groups. Transplant-related mortality was 9.6% and 13% in 'purged' and 'unpurged' groups. Median follow up was 11 months (2-71) and overall actuarial probability of disease-free survival (DFS) at 5 years was 40% (53% relapse probability). We found a beneficial effect of purging in patients over 15 years of age and in patients needing more than 1 month to reach CR1. Patients in CR1 receiving purged marrow had a longer DFS and a lower relapse probability (52% vs 12%, P = 0.02 and 35% vs 86%, P = 0.005, respectively) which were related to the efficacy of the purging procedure (more or less than one log of depletion). In further CR, no advantage of purging has been found. Our data strongly suggest the clinical relevance of BM purging in autologous BMT in high-risk ALL patients and support the need for prospective randomized studies.

Bone marrow purging in acute lymphoblastic leukemia: biological and clinical features.

A group of 56 patients with immunophenotyped acute lymphoblastic leukemia had their bone marrow purged using monoclonal antibody (MAb) and complement. Mononuclear marrow cells were treated with panels of MAb directed against T cells (n = 19), CD10-CALLA (n = 16), and B cells (n = 21), resulting in median specific cell depletions of 96.50, 97.59, and 96.97%, respectively. The resulting CFU-GM recoveries were 60.15, 110.6, and 72.9%. Long-term bone marrow cultures showed normal formation of adherent cell layers in 17 of 23 cases, and failure to form an adherent layer correlated with poor hematological reconstitution. A total of 32 patients (aged 4-40 years) received purged marrow grafts containing a median of 1.32 x 10(7) mononuclear cells/kg and 1.64 x 10(4) CFU-GM/kg; 7 patients required backup marrow. Time to engraftment of 500 granulocytes, 1000 leukocytes, 20,000 platelets, and 50,000 platelets was 37, 38, 39, and 57 days, respectively. A total of 16 patients (50%) remain alive and in complete remission 313-913 days posttransplant (median 565 days); 13 patients (41%) relapsed between 50 and 365 days posttransplant (median 100 days), and 3 patients (9%) died from transplant-associated complications.

Autologous bone marrow transplantation for acute leukemia: results and prognostic factors in 90 consecutive patients.

The results of autologous bone marrow transplantation (ABMT) in acute leukemia (AL) and the prognostic factors for outcome were analyzed in a series of 90 consecutive patients treated at a single institution (mean +/- SD age: 25 +/- 11 years). Diagnosis was: AML (n = 43), ALL (n = 44), acute undifferentiated leukemia (n = 2) and acute bilineage (n = 1). Disease stage at ABMT was: first complete remission (CR1) 46 cases, CR2 33, other stages 11. Conditioning consisted of cyclophosphamide and total body irradiation in 88 patients. The 3 year probability of disease-free survival (DFS) was influenced by disease stage at ABMT: CR1 48%, CR2 28%, CR3 plus CR4 15%. The characteristics associated with a high probability of relapse were: in AML a FAB subtype other than M1 or M3 (p = 0.01) and in ALL an interval between CR1 and ABMT of < 3 months (p = 0.002). A WBC > 15 x 10(9)/l at diagnosis (p = 0.01), splenomegaly at diagnosis (p = 0.002) and time to CR1 > 4 weeks (p = 0.06) increased the risk of relapse in the entire group in CR1. In multivariate analysis, WBC at diagnosis (p = 0.006) and disease stage at ABMT (p = 0.03) independently influenced DFS. This study confirms the encouraging results of ABMT in CR1 but further antileukemia measures are necessary in patients with adverse prognostic features.

Hematological recovery after autologous bone marrow transplantation in acute leukemia: predictive factors.

The kinetics of hematological recovery after autologous marrow transplantation have been studied in 70 patients with acute leukemia (38 acute nonlymphoblastic leukemia [ANNL] and 32 acute lymphoblastic leukemia [ALL]). The incidence of graft failure in this group was 3.2%, and a persistent severe thrombocytopenia was observed in 24% of the cases. Variables influencing engraftment have been studied using univariate and multivariate statistical analysis. Analysis of the entire group showed a correlation between graft colony-forming unit granulocyte-macrophage (CFU-GM) content and granulocyte recovery (p < 0.001). Marrow purging was associated with a delayed engraftment (p < 0.001). In ANLL patients, we found that high cummulated AraC doses before marrow cryopreservation correlated with poor granulocyte recovery after marrow infusion (p < 0.002). Platelet recovery was essentially affected by age, with shorter thrombocytopenia periods in younger patients (p < 0.001). Finally, excluding autotransplants with purged marrows, ALL patients showed better platelet recoveries than ANLL patients (p < 0.005). These findings will be useful to evaluate the risk of delayed engraftment after autologous bone marrow transplantation (ABMT) in patients with acute leukemia.

[Bone marrow autotransplant: preliminary results in 20 patients with acute leukemia]. / Autotrasplante de medula ósea: resultados preliminares en 20 pacientes con leucemia aguda.

The results of bone marrow autograft (BMAG) in 20 patients with acute leukemia (AL) consecutively treated from October 1985 and May 1988 are reported. The follow up was continued until November 1988. The mean age of the patients was 20 years (range 10-48) and their diagnoses were acute myeloblastic leukemia (AML) in 12 and acute lymphoblastic leukemia (ALL) in 8. The preparation for BMAG included cyclophosphamide and whole body radiation in all cases. The procedure was carried out in the first complete remission (CR-1) in 5 patients, in CR-2 in 11, in CR-3 in 2, and in CR-4 in another 2. Two patients died as a direct consequence of BMAG, 11 relapsed and 7 are alive and free from relapse. The likelihood of survival free from prolonged illness was calculated as 24% for the whole series, 60% for the cases of BMAG in CR-1 and 50% for the group of patients with AML. The results were poor in the cases of BMAG carried out for AL in an advanced stage. On the basis of these results the experience of other authors with this therapeutic modality is reviewed, and its current indications are discussed.