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

Abstract

Summary:From 1984 to 1996, 31 consecutive children without sibling donors, aged 5-19 years (median 8) with acute lymphoblastic leukaemia (ALL) in second complete remission (CR), received unpurged autologous bone marrow transplantation (ABMT) after melphalan and single fraction total body irradiation (TBI). ABMT was performed using fresh unmanipulated marrow harvested after standard reinduction and consolidation therapy 2-11 months (median 5) after relapse. With a median survival of 2.9 years the probability of survival for all patients in continuing second CR was 45.1% (95% CI, 24%-62%) after 5 years. Regimen-related and non-leukaemia mortality was 7% (95% CI, 2%-26%). The longest time to second relapse from ABMT was 3.1 years. Pituitary and gonadal dysfunction requiring hormonal replacement therapy occurred in the majority of long-term survivors. Twelve patients developed cataracts. ABMT with melphalan/single fraction TBI has proved an effective anti-leukaemia treatment with low regimen-related mortality but significant long-term morbidity. The current approach of allogeneic BMT from an unrelated donor when no sibling donor is available, following conditioning with cyclophosphamide/ fractionated TBI has resulted in a reduced relapse rate and improved short-term overall survival in the treatment of relapsed childhood ALL. However, long-term results are awaited. Bone Marrow Transplantation (2000) 25, 599-603. Keywords: childhood ALL; autologous BMT; melphalan/TBI; second remission Childhood acute lymphoblastic leukaemia (ALL) is curable in 60-70% of patients in first complete remission (CR) with first-line therapy. 1,2 However, the outcome of children in second or subsequent CR is much less favourable following second-line therapy with or without bone marrow transplantation (BMT). 3,4 The two most important factors that affect the long-term prognosis post relapse are the site of relapse (bone marrow vs extramedullary sites) and duration of first remission. 3,4 Allogeneic BMT from an HLA-matched sib-

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.…”

TBI during BM and SCT: review of the past, discussion of the present and consideration of future directions

“…Finally, largely to address problems identifying donors, as well as higher side-effect profiles for patients receiving unrelated donor marrow, research in the 1980s led to development of autologous SCT techniques. These allowed patients to receive their own stem cells with no concern for immunocompatibility [13][14][15][16] (Table 1).…”

Long-term renal function following bone marrow transplantation

“…[1][2][3][4][5][6][7][8] The growing number of patients who have survived childhood malignancy has increased the importance of monitoring the long-term side effects. Acute renal impairment is a major side effect of BMT, often leading to permanent renal failure.…”