Outcome of Treatment in Children with Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

Aricò, Maurizio; Valsecchi, M.G.; Camitta, Bruce M.; Schrappe, Martin; Chessells, Judith M.; Baruchel, André; Gaynon, P. S.; Silverman, Lauren; Janka‐Schaub, Gritta; Kamps, Willem A.; Pui, CH; Masera, Giuseppe

doi:10.1056/nejm200004063421402

Cited by 532 publications

(369 citation statements)

References 35 publications

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“…15,33,65 The percentage of patients found prednisone resistant may vary, but the prognosis is uniformly inferior to that of the corresponding patients with PGR. PPR can be used to adapt treatment intensity, 17,21,32 to identify HR subsets of Ph þ ALL 65,66 and to target alloSCT to very-high-risk subgroups of T-ALL. 24 (6) The role of alloSCT in first CR is limited to very-high-risk patients.…”

Section: Discussionmentioning

confidence: 99%

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

Möricke¹,

Zimmermann

Reiter³

et al. 2009

Leukemia

468

303

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Section: Discussionmentioning

confidence: 99%

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

Möricke¹,

Zimmermann

Reiter³

et al. 2009

Leukemia

468

303

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“…3,16 Of the 32 patients, 6 were considered high-risk (WBC4100 k, any age), 8 low-risk (WBCo50 k, ageo10 years) and the remaining 18 patients were intermediate-risk (WBCo100 k, any age). Fifteen patients received imatinib therapy either pre-or post-HCT (9 pre-HCT, 2 pre/ post-HCT, 2 post-HCT and 2 pre-HCT and at relapse) comprising the imatinib group, whereas the remaining 17 patients either never received imatinib (n ¼ 11) or received it only at the time of relapse post-HCT (n ¼ 6) were the nonimatinib group (Table 1).…”

Section: Methodsmentioning

confidence: 99%

“…Disease-free survival (DFS) using standard chemotherapy is reported to be 25-30% in children and less than 20% for adults. 3 Earlier studies have shown that allo-hematopoietic cell transplant (HCT) from a matched-related donor decreases relapse rates, resulting in improved DFS to 40-60%. [4][5][6][7] At the gene level, the Ph þ chromosome is created by a translocation of the 5 0 portion of the bcr gene to the kinase domain of the abl gene, resulting in a novel fusion protein with unregulated tyrosine kinase (TK) activity.…”

Section: Introductionmentioning

confidence: 99%

Allo-hematopoietic cell transplantation for Ph chromosome-positive ALL: impact of imatinib on relapse and survival

Burke

Trotz

Luo

et al. 2008

Bone Marrow Transplant

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The utility of imatinib in either the pre-or post-transplant period for Ph chromosome-positive (Ph þ ) ALL is uncertain. In addition, there have been recent concerns regarding imatinib and cardiac toxicity. We investigated the outcome of 32 patients with Ph þ ALL who received an allo-hematopoietic cell transplant (HCT) at the University of Minnesota between 1999 and 2006. The median age at HCT was 21.9 years (range: 2.8-55.2). All patients were conditioned with CY and TBI. GVHD prophylaxis was CsA based. Of the 32 patients, 15 received imatinib therapy pre-or post-HCT (imatinib group) and 17 patients received either no imatinib (n ¼ 11) or only after relapse (n ¼ 6) (non-imatinib group). Overall survival, relapse-free survival and relapse at 2 years was 61, 67 and 13% for the imatinib group as compared with 41, 35 and 35% for the non-imatinib group (P ¼ 0.19, 0.12 and 0.20, respectively). Cardiac toxicity and TRM at 2 years were similar between groups. Thus, patients treated with imatinib in either the pre-or post-transplant setting had trends toward improved outcomes and no increase in cardiac toxicity. We suggest that imatinib be included in the peri-transplant management of all patients with Ph þ ALL.

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“…3 In a retrospective analysis, children with translocation t(9;22) undergoing SCT from an HLA-identical sibling donor achieved 65% EFS, which is significantly better than the outcome from chemotherapy, 25% EFS. 4 Fewer relapses among the SCT recipients accounted for the improved outcome. More recent prospective multi-institution clinical trials corroborate the advantage of SCT.…”

Section: Sct In First Remissionmentioning

confidence: 99%

Transplantation for children with acute lymphoblastic leukemia

Krance

2008

Bone Marrow Transplant

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EFS for children with ALL continues to increase and is predicted to reach 90% with current therapy. Better understanding of leukemia cell biology and pharmacogenetics has led to the design of more effective treatment and also refined the prognostic features associated with a poor outcome. ALL characterized by the translocation t(9;22) or t(4;11), or by a hypodiploid karyotype or by an incomplete response to induction therapy is likely to relapse. SCT for ALL is largely used to treat patients failing primary chemotherapy but is selectively included as part of initial therapy for children at high risk for relapse. If SCT is going to become the primary therapy for children with ALL in first remission, the regimen-related mortality must approach 0%, and the risk for severe acute and chronic GVHD should be less than 5%. Salvage therapy after ALL relapse remains the major indication for SCT. The time required to find a suitable match has led to the use of cord blood and haploidentical related donors as stem cell sources. For children who relapse, SCT is likely to remain the principal option to promote survival. Efforts to reduce both the risk of relapse and the transplant regimen toxicity, both immediate and delayed, must continue.

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Outcome of Treatment in Children with Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia

Cited by 532 publications

References 35 publications

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

Long-term results of five consecutive trials in childhood acute lymphoblastic leukemia performed by the ALL-BFM study group from 1981 to 2000

Allo-hematopoietic cell transplantation for Ph chromosome-positive ALL: impact of imatinib on relapse and survival

Transplantation for children with acute lymphoblastic leukemia

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