Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials

We reviewed 70 consecutive children with AML who received hematopoietic stem cell transplantation (HSCT) in our institution between 1994 and 2005. Forty-seven children were transplanted in CR1 and 23 were transplanted in CR2. BU/CY was the most common pretransplant conditioning regimen for CR1 patients and a TBI-based conditioning regimen was the most common regimen for CR2 patients. Most patients transplanted in CR1 (81%) received related donor HSCT, whereas most of the CR2 patients (74%) received unrelated donor HSCT. Expectedly, there was a significant increase in acute GVHD incidence in CR2 patients (40 vs 25% for grades I-II and 30 vs 10% for grades III-IV; P ¼ 0.02) and a significant increase in transplant-related mortality (38 vs 11%; P ¼ 0.01). Although the difference between 3-year EFS for CR1 and CR2 was not statistically significant, there was a significantly superior 3-year overall survival for CR1 patients (74 vs 51%; P ¼ 0.05). Children with relapsed AML who achieve and maintain remission until HSCT, have a reasonable survival, but the outcome of children receiving HSCT in CR1 remains superior.

Section: Discussionmentioning

confidence: 76%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

A comparison of the outcomes of children with acute myelogenous leukemia in either first or second complete remission (CR1 vs CR2) following allogeneic hematopoietic stem cell transplantation at a single transplant center

Gassas

Ishaqi

Afzal

et al. 2008

“…Nevertheless, randomization between transplantation and chemotherapy is hardly feasible and likely to fail, as shown earlier by other groups in the same or different settings. 62,63 Treatment assignment in ongoing ALL relapse trials is mostly MRD based; chemotherapy plus cranial irradiation is planned for patients with MRD levels lower than 1 Â 10 3 (low risk) after induction and allogeneic transplantation for those with MRD levels higher than 1 Â 10 3 (high risk), whose EFS would be lower than 20% with chemo/ radiotherapy only. 34,64,65 Assessing the best available treatment for ALL in CR2 and defining the role of autologous transplantation is beyond the purpose of this study.…”

Section: Discussionmentioning

confidence: 99%

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

Balduzzi

Bonanomi

Valsecchi

et al. 2010

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.

“…Allo-SCT was advocated for 'poor'-risk children, including children with more than 15% blasts in the BM after the first course of chemotherapy; those with adverse cytogenetic abnormalities of À5, À7, del(5q) and abn(3q); and those with complex karyotype and without favorable genetic abnormalities (t(8;21), inv (16), t (15;17)). 1 However, SCT using conditioning with TBI 1440 cGY and CY 120 mg/kg did not translate into an improved disease-free survival, and the use of unrelated donors in 'poor'-risk patients was associated with a significant TRM. 2 Most children with relapsed AML proceed to SCT once a second CR has been achieved; up to 40% of children are salvaged in this way.…”

Section: Introductionmentioning

confidence: 99%

Successful outcome of allo-SCT in high-risk pediatric AML using chemotherapy-only conditioning and post transplant immunotherapy

Bonanomi

Connor

Webb

et al. 2008

Self Cite

We report successful outcome in 13 children (median age 2.2 years) with high-risk AML who received SCT from an unrelated (11) or identical sibling (2) donor after a preparative regimen consisting of BU, CY and melphalan. Three children were 'poor'-risk in first CR, three in the second CR, five in PR and two had resistant disease. Immunotherapeutic strategies were employed to maximize a GVL response escalating through a reduced dose of alemtuzumab, early taper of CsA, donor lymphocyte infusion and treatment with a-IFN. Ten out of 13 (77%) children are alive in CR at a median of 41 months (range: 17-88) from SCT. There was no TRM, but three children relapsed and died 3, 4 and 17 months after SCT. These encouraging early results warrant further studies in children with very high-risk AML.