Autologous bone-marrow transplants compared with chemotherapy for children with acute lymphoblastic leukaemia in a second remission: a matched-pair analysis

Summary:We present a retrospective study of long-term outcome and predictive factors of survival and relapse in 219 paediatric patients with acute lymphoblastic leukaemia (ALL) in second remission. They received allogeneic (allo) or autologous (auto) haemopoietic cell transplantation (HCT) depending on the availability of a matched sibling donor. The probability of event-free survival (EFS) for the total patient group was 0.35 þ 0.03 at 14 years. No significant differences were observed for EFS between allo-and auto-HCT: 0.39 þ 0.05 vs 0.32 þ 0.04 (P ¼ 0.43). A better EFS was seen in patients with a late relapse (LR) (P ¼ 0.06 and 0.02, for allogeneic and autologous respectively). Significantly better EFS was observed in allo-HCT patients under 10 years of age and in auto-HCT patients with leukocytes at diagnosis below 25 Â 109/l and late relapse. Predictive factors of failure in both groups were early relapse (ER), medullary relapse and age over 10 years. The probability of relapse (RP) for the total group of patients was 0.57 þ 0.03, and it was significantly higher in auto-HCT patients: 0.65 þ 0.04 vs 0.42 þ 0.06 (P ¼ 0.002). Factors predictive for relapse were medullary and early relapse, auto-HCT and WBC 425 Â 109/l at diagnosis. The intensive chemotherapy regimen presently used for childhood lymphoblastic leukaemia allows a prolonged disease-free survival in more than 70% of patients. 1 Relapse is observed in approximately 20-25% of patients, mostly within the first 5 years after diagnosis. 2,3 Optimal therapy for relapsed patients remains controversial in some areas. 4 With the use of intensive chemotherapy, 80-95% of patients achieved a complete second remission. However, less than 5% of the patients with an early relapse (during therapy or within 30 months of diagnosis) and 25-40% of those with a late relapse (after 6 months of completion of therapy or as of 30 months since diagnosis) are long-term survivors. 5-7 Allogeneic haemopoietic cell transplantation (allo-HCT) from a matched sibling donor has been shown to be superior to chemotherapy, especially for patients with an early relapse; 8-13 for late isolated extramedullary relapse, chemotherapy alone may play a role. 14,15 However, the lack of a compatible matched sibling donor limits the use of this treatment. The safety and efficacy of autologous HCT (auto-HCT) in children with acute lymphoblastic leukaemia (ALL) has been previously reported. [16][17][18][19][20][21][22] Comparison studies of auto-and allo-HCT have suggested different failure patterns, but comparable survival rates. Auto-HCT offers the advantages of an accelerated immunological recovery and the absence of graft-versus-host disease (GVHD) compared with allo-HCT. By contrast, a higher relapse rate is observed in patients receiving an autologous transplant. [23][24] However, the heterogeneity of populations used for comparison (stage of disease, risk factors, prior therapy, conditioning regimens) makes it difficult to reach any conclusions which may be useful in therapeutic decision-ma...

Section: Discussionsupporting

confidence: 81%

Long-term outcome of allogeneic or autologous haemopoietic cell transplantation for acute lymphoblastic leukaemia in second remission in children. GETMON experience 1983–1998

Badell

Muñoz

Ortega

et al. 2005

“…[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.…”

Section: Discussionmentioning

confidence: 99%

“…[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.…”

Section: Introductionmentioning

confidence: 99%

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

Balduzzi

Bonanomi

Valsecchi

et al. 2010

Self Cite

The treatment of childhood B-cell-precursor ALL after isolated-extramedullary or late relapse is controversial. Most approaches are based on chemotherapy or allogeneic transplantation. The aim of this report is to assess the long-term outcome of children with 'low-risk' relapsed ALL treated according to a prospective purified autotransplantation protocol. From January 1997 to March 2004, at a single pediatric Center, 30 ALL consecutive children, lacking an HLA-identical sibling, were treated according to the autologous purified peripheral blood stem cell protocol after isolated-extramedullary (7) or late medullary (24) relapse. After the 'DIAVE' mobilizing regimen a median of 11.6 Â 10 6 CD34 þ /Kg (range 3.9-27.4) were collected. Leukaphereses were depleted by 99% of CD19 þ cells (range 98-100) by means of a double step immunological purification. The conditioning regimen included TBI. No early severe complications nor transplant-related deaths occurred; late effects, as expected, mostly consisted in endocrinological issues and were assessed at a median follow-up of 8.5 years. Five-year-EFS and survival were 68.5% (s.e. 7.9) and 85.7% (s.e. 5.9), respectively, for the 35 eligible patients and 70.0% (s.e. 8.4) and 86.7% (s.e. 6.2) for the 30 patients actually transplanted as per protocol. The outcome of this series favorably compares with historical data regarding both autologous transplantation and standard salvage chemotherapy.

“…[1][2][3] When a compatible related donor is not available, it is still controversial when highdose chemotherapy followed by autologous HSC rescue or allogeneic transplantation from an alternative donor should be undertaken, according to the prognosis of the disease. 4,5 For children with acute lymphoblastic leukemia (ALL) in second complete remission (CR2) after a late relapse or with acute non-lymphoblastic leukemia (ANLL) in first CR (CR1) the prognosis is not usually so dismal as to make allogeneic transplantation from an alternative donor acceptable, due to the transplant-related morbidity and mortality rates which are still high. High-dose chemotherapy followed by autologous stem cell rescue may then be considered as an alternative to 'conventional' chemotherapy.…”

mentioning

confidence: 99%

Peripheral blood stem cell collection in children with acute leukemia: effectiveness of the ‘DIAVE’ mobilizing regimen

Balduzzi

Perseghin

Dassi

et al. 2002

Summary:Few experiences of peripheral blood (PB) hematopoietic stem cell mobilization for autologous transplantation have been reported to date in children with acute leukemia (AL). The five-drug-chemotherapy 'DIAVE' (dexamethazone, idarubicine, cytosine-arabinoside, vincristine, etoposide), followed by G-CSF, previously reported as consolidation, was adopted as a mobilization regimen in 29 children (median age: 8 years, range: 3-21; median weight: 34 kg, range: 15-73) with ALL in second remission (CR2: 21), in CR3 (2) or ANLL in CR1 (6). A median peak of 94 ؋ 10 6 CD34 + cells/l (range: 10-604) was reached at a median time of 12 days (range: 10-18) after the beginning of the mobilizing regimen, which was well tolerated. A median of 10.9 ؋ 10 6 CD34 + cells/kg (range: 2.4-56.6) were collected in 25 patients (86%), approaching 40 ؋ 10 6 /l CD34 + cells in the PB (ALL in CR2: 20/21, in CR3: 0/2; ANLL: 5/6) by means of one (20) or two (5) leukaphereses; a median of 2.5 blood volumes was processed. Patients with ANLL mobilized more cells than patients with ALL; moreover, the shorter the interval between remission and mobilizing therapy, the higher was the yield. The products collected underwent purification, aiming at achieving complete removal of possibly contaminating leukemic cells, in 21 cases; also, unmanipulated aliquots were stored as rescues for all but one patient. All the 23 patients undergoing transplantation engrafted (ANC Ͼ0.5 ؋ 10 9 /l) at a median of 12 days. In conclusion, the DIAVE regimen compares favorably with conventional mobilizing regimens, usually containing cyclophosphamide, in terms of low toxicity, collection time predictability, and efficacy, as shown by the high proportion of patients mobilizing, the large amounts of stem cell collected by means of one or two leukaphereses only, and the prompt engraftment after infusion.