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

Abstract

Summary: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. Keywords: autologous BMT; acute lymphocytic leukemia; bone marrow purging Therapy for acute leukemia has become more and more efficient during the past decade. Most children with acute lymphoblastic leukemia (ALL) can be cured with current chemotherapy strategies. 1-3 Similarly, the majority of patients with acute myeloid leukemia (AML), regardless of their age, can achieve a complete remission (CR) using combined chemotherapy with anthracyclines, cytosine arab- inoside, etoposide, carboplatinum and other drugs in different combinations. [4][5][6] However, many of these AML patients and high-risk ALL patients will never be cured with chemotherapy due to the high incidence of relapse. 5,6 Bone marrow transplantation (BMT) technologies have improved significantly over the past 15-20 years and now constitute a regular therapeutic approach for poor-risk ALL patients. 7,8 Although allogeneic BMT is currently curative for approximately 50% of the patients, [8][9][10][11][12] unfortunately, this kind of transplant can only be applied to those patients having an HLA-identical donor, either family related or unrelated. The probability of finding an HLA-matched donor in a family with at least two children is 25-30%, and unrelated donors can be found for 50% of patients who do not have a family donor. Also the probability of being in CR rapidly decreases during the first 4 to 5 months, which is the median time necessary for a successful search for an unrelated donor. Thus 40-50% of patients will not be eligible for this potentially curative therapeutic option.Autologous BMT is an alternative to allogeneic BMT for many of these patients. 13,14 There are at least two factors that make autologous BMT less likely to be curative when compared to allogeneic t...

Autologous purified peripheral blood SCT in childhood low-risk relapsed ALL

“…[43][44][45][46] This study compares favorably with previous experiences using chemotherapy and historical unmanipulated autografting, reporting EFS ranging from 33 to 56% for CNS relapses, 69% for any extramedullary relapse and from 41 to 61% for late relapses. [12][13][14][15][16][17][18][19][20][21][22][23][24][25] In a previous matched-pair analysis for late medullary relapses, autologous transplantation, reporting an EFS of 41%, was of no benefit, compared with chemotherapy. 20 Patient selection may differ, as T-lineage ALL was excluded from this B-lineage ALL study.…”

“…Analyses were performed by SAS and S-plus. (24) or 2000 (5) frontline protocols; one patient was treated abroad. [35][36][37][38] Mobilization, collection, purification Thirty-one patients were actually enrolled in the mobilization protocol and underwent autologous transplant.…”

“…[10][11][12][13][14] Autologous transplantation may be an alternative to chemotherapy for ALL in CR2 after low-risk relapse. [15][16][17][18][19][20][21][22][23][24][25] In 2001, we reported a study that showed the feasibility and efficacy of an innovative protocol for autologous transplantation of purified peripheral hematopoietic stem cells in 12 pediatric patients with pediatric B-cell-precursor ALL after isolated extramedullary and/or late relapse. 26 This strategy aimed to ensure the best available treatment for low-risk relapsed ALL children and to avoid the toxicity of allogeneic transplantation.…”

Autologous stem cell transplantation in adults with acute lymphoblastic leukemia in first complete remission: analysis of the LALA-85, -87 and -94 trials

“…Some retrospective reports, mostly performed in patients actually receiving ASCT and not based on the intent-to-treat principle, have suggested that ASCT may be associated with prolonged DFS. [17][18][19][20][21][22][23][24][25] However, reported prospective studies enrolling either standard-risk (Truchan-Graczyk et al Blood 2002; 100: 861a, abstract), high-risk, 26,27 or all-risk ALL patients 1,2,28 (and Rowe et al Blood, 2001; 98, 481a, abstract) failed to demonstrate the superiority of ASCT over chemotherapy, perhaps because of the relatively limited populations of patients randomized.…”

The role of maintenance chemotherapy after autotransplantation for acute lymphoblastic leukemia in first remission: single-center experience of 100 patients

“…We have shown 1,2 that results of autologous hematopoietic stem cell transplantation (HSCT) in adult ALL [3][4][5][6][7][8][9][10][11][12][13][14] can be improved by administering post transplant maintenance chemotherapy with 6-mercaptopurine (6-MP), methotrexate and vincristine-prednisone. A recent review of autologous HSCT in ALL 15 suggested that the value of autotransplantation is likely to be underestimated in ALL.…”