Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)–rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

Mann, Georg; Attarbaschi, Andishe; Schrappe, Martin; Lorenzo, Paola De; Peters, Christina; Hann, Ian; Rossi, Giulio De; Felice, Marı́a Sara; Lausen, Birgitte; Leblanc, Thierry; Szczepański, Tomasz; Ferster, Alina; Janka‐Schaub, Gritta; Rubnitz, Jeffrey E.; Silverman, Lewis B.; Starý, Jan; Campbell, Myriam; Li, Chi Kong; Suppiah, Ram; Biondi, Andrea; Vora, Ajay; Valsecchi, Maria Grazia; Pieters, Rob

doi:10.1182/blood-2010-03-273532

Cited by 143 publications

(119 citation statements)

References 31 publications

Supporting

Mentioning

107

Contrasting

Unclassified

Order By: Relevance

“…14 For infants and patients with bcr-abl rearrangement after 2005, indications of HSCT were as described in the INTERFANT and ESPHALL trials. 15,16 Patients with relapsed ALL were treated according to the risk stratification of BFM relapses protocols. 17 For AML patients in CR1, HSCT was recommended for all patients with monosomy 5 or 7, translocation t(6,9) and mixed lineage leukemia rearrangement, except for translocation t(9,11) with related or unrelated donors, and was performed in other cases with matched sibling donors (MSDs) only, except for patients with translocation t (8,21).…”

Section: Patients and Methods Patientsmentioning

confidence: 99%

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

Bleyzac

Cuzzubbo

Rénard

et al. 2016

Bone Marrow Transplant

View full text Add to dashboard Cite

There is currently a major concern regarding the optimal immunosuppression therapy to be administered after hematopoietic stem cell transplantation (HSCT) to reduce both the toxicity of GvHD and the rate of relapse. We report the outcome of high-risk leukemia children transplanted with a new way of managing cyclosporine (CsA)-based GvHD prophylaxis. A total of 110 HSCT in 109 ALL or AML children who received CsA without mycophenolate or methotrexate in matched related as well as in matched or mismatched unrelated stem cell transplantation were included. CsA dosage regimens were individualized to obtain specific trough blood concentrations values. The incidences of grade I-II and III-IV acute GvHD were 69.1% and 1.8%, respectively, and 8.4% for chronic GvHD. GvHD was neither more frequent nor severe in unrelated than in related HSCT. GvHD occurred in 87% of patients with a mean CsA trough concentration ⩽ 120 ng/mL versus 43% with concentration 4120 ng/mL (Po 0.0001). Five-year disease-free survival (DFS) and overall survival were 78% and 83.6%, respectively. DFS was 76.9% for ALL and 80.4% for AML patients. There was no difference in DFS between matched siblings and matched unrelated or mismatched unrelated HSCT. DFS in patients with minimal residual disease (MRD) ⩾ 10 − 3 and in those with MRD o 10 − 3 before SCT was comparable. Our results indicate that a GvHD prophylaxis regimen based on CsA without mycophenolate or methotrexate is safe and effective whatever the donor compatibility is. These results suggest that GvL effect may be enhanced by this strategy of GvHD prophylaxis.

show abstract

Section: Patients and Methods Patientsmentioning

confidence: 99%

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

Bleyzac

Cuzzubbo

Rénard

et al. 2016

Bone Marrow Transplant

View full text Add to dashboard Cite

show abstract

“…The authors concluded that HSCT should be considered in CR1 due to risk for unsuccessful salvage post-relapse and poor survival rates for HSCT in CR2. Over the years the paradigm appears to have shifted from HSCT in CR1 to more intensive multiagent chemotherapy for previously considered HR patient groups (20)(21)(22)(23). But at the same time, the definition of HR leukemia is changing given recent discoveries with new genomic lesions and continued MRD testing.…”

Section: Contextmentioning

confidence: 99%

“…Previous studies have identified younger age at diagnosis (< 6 months of age), MLL (mixed lineage leukemia) rearrangement, high presenting WBC (> 300,000 µL/mL) and poor prednisone response as poor prognostic factors for infants (21,45,47). Historical data would suggest transplant in CR1 is advantageous for infants with MLL-R ALL.…”

Section: Infant Allmentioning

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

View full text Add to dashboard Cite

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.

show abstract

“…15 The use of SCT to intensify therapy for infants has not shown clear benefit, but the risk of relapse may be reduced for those in the highest risk group. 16,77 TRM in high-risk ALL Morbidity, both short-term and long-term, affects every patient treated for ALL. Despite improvements in supportive care, mortality as a consequence of therapy persists as a cause of death.…”

Section: Treatment For High-risk Allmentioning

confidence: 99%

“…14 Infants, those Ͻ1 year of age at the time of diagnosis, remain at very high risk of relapse, even with aggressive contemporary therapy. 15,16 Risk stratification within the infant group is based on presence of MLL gene rearrangement, found in ϳ75% and in the majority of younger infants. In addition, months of age at the time of diagnosis, with those Ͻ3 or 6 months fairing worse and high presenting WBC (Ͼ100 000 or Ͼ300 000) are important prognostic factors within this group of patients.…”

Section: Clinical Featuresmentioning

confidence: 99%

Clinically defining and managing high-risk pediatric patients with acute lymphoblastic leukemia

Alexander

2014

Hematology

View full text Add to dashboard Cite

For children with acute lymphoblastic leukemia, the identification of those at higher risk of disease recurrence and modifying therapy based on this risk is a critical component to the provision of optimal care. The specific definitions of high-risk ALL vary across cooperative groups, but the themes are consistent, being largely based on leukemia biology and disease response. Intensification of conventional chemotherapy for those with high-risk disease has led to improved outcomes. It is anticipated that the development of rational targeted therapy for specific biologically unique subsets of children with leukemia will contribute to ongoing progress in improving the outcomes for children with acute lymphoblastic anemia. Learning Objectives• To understand current criteria used to identify children with high-risk ALL • To understand therapeutic strategies for children with highrisk ALL

show abstract

Improved outcome with hematopoietic stem cell transplantation in a poor prognostic subgroup of infants with mixed-lineage-leukemia (MLL)–rearranged acute lymphoblastic leukemia: results from the Interfant-99 Study

Cited by 143 publications

References 31 publications

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

Improved outcome of children transplanted for high-risk leukemia by using a new strategy of cyclosporine-based GVHD prophylaxis

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

Clinically defining and managing high-risk pediatric patients with acute lymphoblastic leukemia

Contact Info

Product

Resources

About