A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial

Lauer, Stephen J.; Shuster, Jonathan J.; Mahoney, Donald H.; Winick, Naomi J.; Toledano, Stuart; Munoz, Louis L.; G, Kiefer; Pullen, Jeannette; Steuber, C. Philip; Camitta, Bruce M.

doi:10.1038/sj.leu.2402132

Cited by 28 publications

(26 citation statements)

References 33 publications

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“…23 In the Pediatric Oncology Group studies, among patients with B-cell precursor ALL, only those with CNS-3 status received craniospinal irradiation (24 Gy cranial and 15 Gy spinal). 24 In Study XIIIB, only 12% of the patients received cranial irradiation, compared with 22% of those in Study XIIIA. The cumulative risks of isolated CNS and isolated plus combined CNS relapse remained low in this study, compared with those in Study XIIIA: 1.7% versus 1.2%, and 3.0% versus 3.2%, respectively.…”

Section: Discussionmentioning

confidence: 92%

Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital

Pui

Sandlund

Pei

et al. 2004

Blood

420

341

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St Jude Total Therapy Study XIIIB for childhood acute lymphoblastic leukemia (ALL) incorporated more stringent risk classification, early intensification of intrathecal chemotherapy, reinduction treatment, and the addition of dexamethasone to postremission therapy to increase the proportion of event-free survivors without jeopardizing their quality of life. Cranial irradiation was reserved for the 12% of patients who had T-cell ALL and a presenting leukocyte count of 100 ؋ 10 9 /L or more, or CNS-3 (5 or more leukocytes/L with identifiable blast cells in an atraumatic sample or the presence of cranial nerve palsy) status. Among the 247 consecutive patients enrolled in the study, 117 were classified as having lowerrisk leukemia and received mainly antimetabolite-based continuation therapy; the 130 cases with higher-risk leukemia received more intensive continuation chemotherapy with multiple drug pairs administered in weekly rotation. The 5-year event-free survival estimate was 80.8% ؎ 2.6% (SE); the 8-year rate was 78.6% ؎ 5.8%. The 5-year cumulative risk of an isolated central nervous system (CNS) relapse was 1.7% ؎ 0.8%, and that of isolated plus combined CNS relapse was 3.0% ؎ 1.1%. The 5-year cumulative risks of etoposide-related myeloid malignancies were 1.8% ؎ 1.3% in the lowerrisk patients who received a cumulative dose of 1.2 g/m 2 and 5.0% ؎ 2.0% in the higher-risk patients who received a cumulative dose of up to 14.4 g/m 2 (P ‫؍‬ .18). Independent adverse prognostic features included the presence of MLL-AF4 or BCR-ABL fusion gene and minimal residual leukemia of 0.01% or more at the end of the 6-week remission induction phase. Our results suggest the efficacy of early intensification of intrathecal chemotherapy and provide the basis for studies omitting cranial irradiation altogether.

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Section: Discussionmentioning

confidence: 92%

Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital

Pui

Sandlund

Pei

et al. 2004

Blood

420

341

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“…POG 9006 attempted to study this question. 12 There was inconclusive benefit to rotating pairs when compared to repeated IDMTX for consolidation. This could mean that the Goldie-Coldman hypothesis is incorrect.…”

Section: Discussionmentioning

confidence: 99%

Long-term results of treatment studies for childhood acute lymphoblastic leukemia: Pediatric Oncology Group studies from 1986–1994

et al. 2000

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This paper presents the long-term results of treatment for children with acute lymphoblastic leukemia (ALL) as conducted by the Pediatric Oncology Group (POG) from 1986 to 1994. The data are presented using standard NCI/Rome risk criteria. The overall event-free survival (EFS) at 5 and 10 years were 70.9% and 67.3% for children with B-precursor ALL, 51.0% and 50.2% for patients with T cell ALL, and 22.4% and 20.9% for infants with ALL. Concomitant biologic studies found that in B-precursor ALL a DNA index (DI) of у1.16 and trisomies of both chromosomes 4 and 10 were good prognostic indicators for patients with B-precursor ALL. The traditional prognostic indicators (age and white count), DI and trisomies did not predict outcome in patients with T cell disease. Infants continued to do poorly overall despite more intensive therapy with rotating pairs of chemotherapy. We recommend continued reporting of study results using common risk criteria in order to facilitate comparisons both within and across study groups. Leukemia

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“…6 More recently, CNS irradiation has been replaced with systemic high-dose MTX, extended IT or additional doses of IT for prophylaxis for most low-risk ALL patients and even some high-risk patients in some protocols. [10][11][12][13][14] Regardless of these measures, approximately 1-7% of ALL patients still develop CNS relapse. 3,[7][8][9] ALL patients with CNS relapse have typically been treated with systemic re-induction chemotherapy and triple intrathecal therapy (MTX/cytosine arabinoside (Ara-C)/hydrocortisone, TIT) followed by cranial or cranio-spinal irradiation and systemic maintenance therapy; 6 however, hematopoietic stem cell transplantations (SCT) have recently been performed in a limited number of patients.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic stem cell transplantation in children with acute lymphoblastic leukemia after isolated central nervous system relapse: our experiences and review of the literature

Yoshihara

Morimoto

Kuroda

et al. 2005

Bone Marrow Transplant

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The prognosis of patients with acute lymphoblastic leukemia (ALL) and central nervous system (CNS) relapse has historically been very poor. Although chemoradiotherapy has improved outcomes, some patients still have a poor prognosis after CNS relapse. Therefore, allogeneic hematopoietic stem cell transplantation (allo-SCT) has recently become an option for treatment of CNS leukemia; however, information, particularly on the long-term outcome of transplant recipients, is limited. We performed allo-SCT in eight pediatric patients with ALL (n ¼ 7) or T-cell type non-Hodgkin's lymphoma (n ¼ 1), who had isolated CNS relapse. All patients survived for a median of 70.5 (range, 13-153) months after SCT. Sequelae developed late in some patients: mental retardation (IQ ¼ 47) in one patient, severe alopecia in two patients, limited chronic graft-versus-host-disease in three patients, and amenorrhea and/or hypothyroidism in three patients. Except for a pre-school child with post transplant CNS relapse, six out of seven patients show normal school/social performance. Our results clearly indicate a high cure rate of isolated CNS relapse by allo-SCT in pediatric lymphoid malignancies; however, there needs to be further studies to determine which are the appropriate candidates for transplantation and what is the best transplant regimen to achieve high cure rate and maintain good quality of life.

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A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial

Abstract: A prospective, randomized multicenter study was performed to evaluate the relative efficacy of two different concepts for early intensive therapy in a randomized trial of children with B-precursor acute lymphoblastic leukemia (ALL) at high risk (

Cited by 28 publications

References 33 publications

Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital

Improved outcome for children with acute lymphoblastic leukemia: results of Total Therapy Study XIIIB at St Jude Children's Research Hospital

Long-term results of treatment studies for childhood acute lymphoblastic leukemia: Pediatric Oncology Group studies from 1986–1994

Allogeneic stem cell transplantation in children with acute lymphoblastic leukemia after isolated central nervous system relapse: our experiences and review of the literature

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