Autologous bone marrow transplantation for treatment of isolated central nervous system relapse of childhood acute lymphoblastic leukemia

Abstract

Summary:The purpose of this study was to assess the role of ABMT in children with ALL who are in 2nd CR after an early isolated CNS relapse. All children experiencing an isolated CNS relapse at 10 AIEOP centers (Associazione Italiana Emato-Oncologia Pediatrica) from 1986 to 1992 were eligible for this study. The series included 69 patients who relapsed within 3 years from diagnosis: 19 underwent ABMT, nine patients underwent ALLO-BMT from an HLA-identical sibling, and 41 received conventional chemotherapy (CHEMO). Statistical analysis was performed using a Cox's regression model, adjusting for the waiting time before transplantation and prognostic factors. The 5 years DFS was 56.3% (s.e. 12.3) for patients in the ABMT group. This compared favorably with the poor result (12.6% (s.e. 5.9) ) seen in the CHEMO group. The risk of failures was reduced by one-third in the ABMT group as compared to the CHEMO group in the multivariate analysis (P Ͻ 0.01). In the ALLO group four out of nine patients were in CCR 4-5 years post-transplant. This study suggests that ABMT may also represent a valuable therapeutic choice for patients lacking a matched familiar donor in 2nd CR after an early isolated CNS relapse. Keywords: childhood lymphoblastic leukemia; meningeal relapse; autologous marrow transplantation Isolated CNS relapse occurs in 5-10% of children with ALL treated with risk-directed therapy.1,2 In most experiences, patients who despite an adequate front-line CNS prophylaxis experience a meningeal relapse have a poor 3 Retreatment induces a second CR but due to further relapses the event-free-survival (EFS) is in the 20-30% range, with few exceptions.2-8 Successful treatment of CNS relapse must include CNS-directed and intensive systemic therapy. Major CNS problems have been described in long-term survivors after conventional retreatment. 9 The role of BMT in the therapeutic strategy of isolated CNS relapse has only recently been explored, with controversial results.7,10-12 Our study investigates the role of ABMT in a relatively large series of 60 children with ALL, who developed a first isolated CNS relapse early, ie within 3 years of diagnosis. Of these, 19 underwent ABMT, while 41 had chemotherapy only; we also include our limited experience on nine patients who had ALLO-BMT. This retrospective study has been based on the experience of all the AIEOP centers that considered ABMT as a therapeutic option for ALL children after an isolated CNS relapse from 1986 to 1992. The analytical method adopted here aimed to exclude any biases related to the retrospective nature of the study and the waiting time before transplantation. Patients and methods PatientsCNS relapse was defined as the presence in the cerebrospinal fluid of Ͼ5 mononuclear cells per microliter, morphologically identified as lymphoblasts on cytospinning. ABMT and, to a lesser degree, also ALLO-BMT, have been considered as a therapeutic option after an isolated CNS relapse at 10 AIEOP transplantation centers since 1986. From 1986 to 1993, 20 consecutive childre...

Autologous bone marrow transplantation with monoclonal antibody purged marrow for children with acute lymphoblastic leukemia in second remission

“…Similar results with ABMT have been reported in another recent Italian Study which compared ABMT and chemotherapy in CNS relapses. 29 Although no definitive conclusions can be established from these experiences, extramedullary relapses appear to be treatable with ABMT.…”

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.…”

“…[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 bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission – long-term follow-up

“…20 It was suggested that ABMT represents a valuable therapeutic option for patients with no matched sibling in second remission after an isolated CNS relapse. 21 Different conditioning regimens have been used prior to BMT in an attempt to reduce leukaemic relapse without increasing toxicity from BMT. 11 Melphalan and TBI have been used in this institution as a conditioning regimen for more than a decade instead of the more commonly used regimen of cyclophosphamide and TBI.…”