Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Treatment of Pediatric Acute Lymphoblastic Leukemia: Update of the 2005 Evidence-Based Review

Oliansky, Denise M; Larson, Richard A.; Weisdorf, Daniel J.; Dillon, Hildy; Ratko, Thomas A; Wall, Donna A.; McCarthy, Philip L.; Hahn, Theresa

doi:10.1016/j.bbmt.2011.12.585

Cited by 94 publications

(48 citation statements)

References 58 publications

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“…Children and adults with high-risk ALL able to tolerate myeloablative therapy have been noted to have superior survival when TBI-based preparative regimens are used compared with chemotherapy regimens, and TBI is currently recommended in American Society for Blood and Marrow Transplantation guidelines for ALL HCT. [16][17][18][19][20][21][22] Concern has been raised about use of these intensive approaches because of known significant late effects of TBI or cranial irradiation in growing children, and adults have a higher risk of secondary malignancies after TBI-based regimens.…”

Section: Discussionmentioning

confidence: 99%

IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients

Pulsipher

Carlson

Langholz

et al. 2015

Blood

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189

144

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Key Points• IgH-V(D)J NGS-MRD detection pretransplant identifies a cohort at low risk for relapse, for which treatment modification could be considered.• Positive NGS-MRD was highly predictive of relapse and survival as early as 30 days after HCT.Positive detection of minimal residual disease (MRD) by multichannel flow cytometry (MFC) prior to hematopoietic cell transplantation (HCT) of patients with acute lymphoblastic leukemia (ALL) identifies patients at high risk for relapse, but many pre-HCT MFC-MRD negative patients also relapse, and the predictive power MFC-MRD early post-HCT is poor. To test whether the increased sensitivity of next-generation sequencing (NGS)-MRD better identifies pre-and post-HCT relapse risk, we performed immunoglobulin heavy chain (IgH) variable, diversity, and joining (V[D]J) DNA sequences J NGS-MRD on 56 patients with B-cell ALL enrolled in Children's Oncology Group trial ASCT0431. NGS-MRD predicted relapse and survival more accurately than MFC-MRD (P < .0001), especially in the MRD negative cohort (relapse, 0% vs 16%; P 5 .02; 2-year overall survival, 96% vs 77%; P 5 .003). Post-HCT NGS-MRD detection was better at predicting relapse than MFC-MRD (P < .0001), especially early after HCT (day 30 MFC-MRD positive relapse rate, 35%; NGS-MRD positive relapse rate, 67%; P 5 .004). Any post-HCT NGS positivity resulted in an increase in relapse risk by multivariate analysis (hazard ratio, 7.7; P 5 .05). Absence of detectable IgH-V(D)J NGS-MRD pre-HCT defines good-risk patients potentially eligible for less intense treatment approaches. Post-HCT NGS-MRD is highly predictive of relapse and survival, suggesting a role for this technique in defining patients early who would be eligible for post-HCT interventions. The trial was registered at www.clinicaltrials.gov as #NCT00382109. (Blood. 2015;125(22):3501-3508)

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Section: Discussionmentioning

confidence: 99%

IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients

Pulsipher

Carlson

Langholz

et al. 2015

Blood

Self Cite

189

144

View full text Add to dashboard Cite

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“…22 Hence, hematopoietic stem cell transplantation (HSCT) in first remission is still offered to patients with hypodiploid (,44 chromosomes) ALL in many contemporary clinical trials. 23 However, treatment outcome of hypodiploid ALL and many other high-risk genetic subtypes of ALL is not uniformly poor because it depends on other leukemia cell variables (eg, cooperative genomic abnormalities, self-renewal capacity, drug resistance), host factors (eg, pharmacogenetics), and efficacy of postremission treatment regimen. 21 Our Total Therapy Studies XV and XVI relied on MRD measurements for final risk assignment, an approach that may over-ride or lessen the prognostic impact of specific genetic abnormalities of leukemic cells.…”

Section: Mrd-directed Treatment Of High-risk Genetic Subtypes Of All mentioning

confidence: 99%

Minimal residual disease–guided therapy in childhood acute lymphoblastic leukemia

Campana

Pui

2017

Blood

115

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A 3-year-old boy presented with a leukocyte count of 5.9 3 10 9 /L and was found to have near-haploid B-lineage acute lymphoblastic leukemia (ALL) with a 27, X, 1Y, 113, 118, 121 karyotype. He was enrolled in the St. Jude Children's Research Hospital Total Therapy XV study. After 19 days of remission induction therapy with 1 high dose of methotrexate, 14 days of prednisone, 2 doses of vincristine and daunorubicin, and 6 doses of Escherichia coli-derived asparaginase, flow cytometry examination of his bone marrow revealed the presence of minimal residual disease (MRD) amounting to 3 leukemic cells per 10 000 mononucleated cells (0.03%). Upon completion of the remaining remission induction therapy consisting of 1 dose of cyclophosphamide, 14 days of mercaptopurine, and 8 onceper-day doses of cytarabine, he attained a morphologic remission on day 46, with undetectable (,0.01%) MRD by flow cytometry and polymerase chain reaction. Because of the near-haploid ALL karyotype and negative day 46 MRD, he was assigned to receive intensive chemotherapy for 3 years. MRD remained undetectable throughout treatment. He has remained in continuous complete remission for 11.6 years. Case 2A 9-year-old boy presented with a 3-month history of progressive pallor and upper respiratory tract infection. He had no hepatosplenomegaly or mediastinal mass. An abnormal blood count with hemoglobin 3.4 g/dL, leukocytes 4.2 3 10 9 /L with 15% neutrophils, 52% lymphocytes, 33% blasts, and platelets 123 3 10 9 /L prompted a bone marrow examination which disclosed 96% replacement with leukemic lymphoblasts. By flow cytometry, the blasts expressed CD45, surface CD3, CD2, CD7, T-cell receptor g/d, CD11b, and CD13, with a subset of cells positive for CD56, a cell profile indicative of T-cell ALL. He was enrolled on the Total Therapy XV study and began remission induction therapy with high-dose methotrexate followed by prednisone once per day, vincristine once per week, daunorubicin once per week, and E coli-derived asparaginase 3 times per week. On day19 of treatment, 62.9% of bone marrow mononucleated cells were leukemic lymphoblasts by flow cytometry (31% of all cells were blasts by morphology). Three additional doses of asparaginase were given, and the remaining remission induction therapy consisted of cyclophosphamide, mercaptopurine, and cytarabine. On day 46, he attained morphologic remission (with 3% lymphoblasts), but MRD by flow cytometry was 5.82%. After consolidation treatment with 4 courses of high-dose methotrexate plus mercaptopurine as well as 1 course of re-intensification therapy with dexamethasone, etoposide, high-dose cytarabine, and asparaginase, MRD decreased to 0.18%. He attained MRD-negative status (,0.01%) after a second course of re-intensification treatment and subsequently underwent a matched-related allogeneic hematopoietic stem cell transplantation. He has remained in continuous complete remission for 11.9 years.

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“…However, as HSCT outcomes continue to improve over time, its role should be re-assessed, particularly for patients with HR biology who have the poorest predicted response rates to chemotherapy alone (9). An expert panel of the American Society for Blood and Marrow Transplantation (ASBMT) has previously provided treatment recommendations through systematic evidence-based reviews (EBRs) every 5-year for various diseases including pediatric ALL (10) date, published in 2012, provided a position statement for HR subsets of pediatric ALL (11).…”

Section: Contextmentioning

confidence: 99%

“…Although previous studies have reported poor outcomes for this subgroup, there is a paucity of data and indications for HSCT in CR1 are unclear. Despite these limitations, the ASBMT EBR from 2012 recommended considering HSCT in CR1 based on expert opinion (11). A previous retrospective review of 130 patients with hypodiploid ALL was performed in 2007 (31).…”

Section: Severe Hypodiploidymentioning

confidence: 99%

The Role of Hematopoietic Stem-Cell Transplantation in First Remission in Pediatric Acute Lymphoblastic Leukemia: A Narrative Review

Bhatt¹,

Phelan²,

Burke³

2017

J Pediatr Rev

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Context: Survival after allogeneic hematopoietic stem-cell transplantation (HSCT) for children with hematologic malignancies including acute lymphoblastic leukemia (ALL) continues to improve in part due to advancement in HLA typing and enhanced supportive care. Despite improved outcomes with HSCT, the decision to offer it in first remission (CR1) in children with ALL remains a topic of debate and uncertainty. This review aims to discuss the role of HSCT in CR1 for children with high-risk subsets of ALL in the current era. Evidence Acquisition: A thorough review of the literature was performed using electronic databases: PubMed, Google Scholar, and bibliographies. Studies focusing on high-risk subsets of ALL (Primary Induction Failure, Severe Hypodiploidy, Philadelphiachromosome positive ALL, T-Cell ALL, Infant ALL, ALL with persistent minimal residual disease (MRD), and Philadelphia-like ALL) were included. Publications in non-English language were excluded. Results: Based on our review of the current literature, HSCT should be considered in first remission for patients with primary induction failure, severe hypodiploidy, T-cell ALL with poor response, high-risk infant ALL, and persistently positive MRD. In contrast, HSCT in CR1 may not be warranted for patients with early T-cell progenitor ALL or Philadelphia-chromosome positive ALL. Further data are needed to make specific recommendations regarding Philadelphia-like ALL. Conclusions: As our understanding of high-risk leukemia biology continues to develop, the role of HSCT in ALL CR1 will need to be revisited.

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Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Treatment of Pediatric Acute Lymphoblastic Leukemia: Update of the 2005 Evidence-Based Review

Cited by 94 publications

References 58 publications

IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients

IgH-V(D)J NGS-MRD measurement pre- and early post-allotransplant defines very low- and very high-risk ALL patients

Minimal residual disease–guided therapy in childhood acute lymphoblastic leukemia

The Role of Hematopoietic Stem-Cell Transplantation in First Remission in Pediatric Acute Lymphoblastic Leukemia: A Narrative Review

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