Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial

Locatelli, Franco; Nöllke, Peter; Zecca, Marco; Korthof, Elisabeth T.; Lanino, Edoardo; Peters, Christina; Pession, Andrea; Kabisch, H; Uderzo, C; Bonfim, Carmen S.; Bader, Peter; Dilloo, Dagmar; Starý, Jan; Fischer, Alexandra; Révész, Tom; Führer, Monika; Hasle, Henrik; Trebo, Monika; Heuvel‐Eibrink, Marry M. van den; Fenu, Susanna; Strahm, Brigitte; Giorgiani, Giovanna; Bonora, M. Regazzi; Duffner, Ulrich; Niemeyer, Charlotte M.

doi:10.1182/blood-2004-05-1944

Cited by 290 publications

(376 citation statements)

References 47 publications

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“…There are no reports of SCT for JMML from India and in our series three children successfully underwent allogeneic SCT. The leading cause of death following transplantation continues to be leukemia relapse [5]. One of three transplanted children relapsed in our series.…”

Section: Resultsmentioning

confidence: 61%

“…Both patients who received chemotherapy died (one at our centre and second at another centre). The only curative therapy is allogeneic SCT which is able to cure *50 % of patients [5,6]. There are no reports of SCT for JMML from India and in our series three children successfully underwent allogeneic SCT.…”

Section: Resultsmentioning

confidence: 62%

“…Conventional chemotherapy rarely achieves cure [1]. However, survival up to 57-64 % have been reported post allogeneic stem cell transplant (SCT) [5,6]. There is a paucity of outcome data for JMML from India [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Juvenile Myelomonocytic Leukemia in India: Cure Remains a Distant Dream!

Ramzan

Yadav²,

Dhingra³

et al. 2014

Indian J Hematol Blood Transfus

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There is paucity of outcome data regarding juvenile myelomonocytic leukemia from India. We report a series of eight children. Three had monosomy 7 and one had complex cytogenetics. One with Down's syndrome recovered spontaneously. Three refused therapy of whom only one is alive with disease. One died post chemotherapy. Three underwent allogeneic stem cell transplant after protracted delay with funds arranged from various governmental and non-governmental organizations. Of these two died (relapse-1 and intracranial bleed-1) and one is alive and disease free. In India, it's a milestone to reach transplant due to high cost and cure still remains a distant dream.

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Section: Resultsmentioning

confidence: 61%

Section: Resultsmentioning

confidence: 62%

See 1 more Smart Citation

Juvenile Myelomonocytic Leukemia in India: Cure Remains a Distant Dream!

Ramzan

Yadav²,

Dhingra³

et al. 2014

Indian J Hematol Blood Transfus

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“…17 As outcome after treatment by chemotherapy only is also not satisfying, it was decided to choose a particular conditioning regimen consisting of BU, CY and MEL, as it was shown to be effective in patients with juvenile myelomonocytic leukemia and AML. 18 …”

Section: Conditioning Regimenmentioning

confidence: 99%

Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials

Schrauder

Stackelberg

Schrappe

et al. 2008

Bone Marrow Transplant

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The definition of indications for allogeneic SCT in children with high-risk (HR) ALL in the first remission or after the first or subsequent relapse depends on biological features, response to treatment and survival after chemotherapy alone. As the results of frontline and relapse protocols are improving over time, there is a strong need for prospective SCT trials, ensuring a well-standardized procedure regarding all relevant components that are potentially responsible for heterogeneity in post-SCT outcome. Therefore, in 2003, the ALL-BFM and the ALL-REZ BFM Study Group initiated a prospective, international, multicenter trial (ALL- SCT-BFM 2003). This trial will now be extended to a larger consortium, trial ALL-SCT-BFM-international (ALL-SCT-BFMi). Strict rules define HLA-typing, donor selection, conditioning regimen, GvHD prophylaxis and therapy as well as standards of supportive care to reduce treatmentrelated mortality and establish an early GVL effect. Moreover, comprehensive and closely reviewed documentation and serious adverse event reporting shall ensure high study quality. Case-by-case discussions of any fatal or critical course during annual meetings will improve the culture of failure management and lead to modifications of guidelines of supportive care. Finally, the results of these prospective trials will determine the current potential of the different SCT procedures in HR or relapsed childhood ALL.

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“…[1][2][3] Although allogeneic HSCT is the only curative option, relapse rates remain high (35%) and TRM is also unacceptably high (15%) with myeloablative conditioning. 4 Given that the highest rates of EFS in most series are around 50%, newer approaches are needed to lower rates of relapse and TRM. Eradication of malignant clones at the stem cell level is believed to be necessary to cure JMML and HSCT conditioning approaches have historically maximised alkylating agent exposure with this goal in mind.…”

mentioning

confidence: 99%

Myeloablative BU, fludarabine, antithymocyte globulin and low-dose TBI in the treatment of juvenile myelomonocytic leukaemia with allogeneic haematopoietic cell transplantation

Guilcher

Moorjani

Truong

et al. 2014

Bone Marrow Transplant

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Juvenile myelomonocytic leukaemia (JMML) is a rare, aggressive myeloproliferative neoplasm that responds poorly to conventional chemotherapy. [1][2][3] With the exception of rare cases of spontaneous remission seen in children with specific molecular mutations, allogeneic haematopoietic SCT (HSCT) is the only curative therapy. Myeloablative conditioning is widely considered to be essential to eradicate leukaemic clones and to faciliate engraftment. Owing to historically high rates of treatment-related mortality (TRM) in children with JMML, efforts are ongoing to develop newer approaches to HSCT therapy to reduce toxicities, including reduced-toxicity myeloablative conditioning regimens. We present pilot data on three children who underwent HSCT with such an approach.A search of our institutional database was performed, and three patients were identified with a diagnosis of JMML who received a reduced-toxicity regimen. A retrospective chart review of the clinical records of the three cases was subsequently conducted to gather data. The database and clinical records were housed at Alberta Children's Hospital in Calgary, Alberta, Canada. This retrospective study was approved by the University of Calgary Conjoint Health Research Ethics Board.All patients received the same regimen consisting of i.v. BU (4 mg/kg/day once daily, days − 5 to − 2), i.v. fludarabine (50 mg/ m 2 /day, days − 6 to − 2), i.v. rabbit ATG (0.5 mg/kg on day − 3 and 2.5 mg/kg/day on days − 2 and − 1) and 400 cGy of TBI on day − 1. BU pharmacokinetics were calculated based on an institutional practise of test dosing before the administration of full dosing, usually day − 7. The target area under the curve (AUC) was 3800 μM Á min. GVHD prophylaxis consisted of CYA in combination with MTX for live donor stem cell products or methylprednisolone for umbilical cord blood (UCB) infusions. Filgrastim was given post HSCT with UCB products. Institutional antimicrobial prophylaxis included acyclovir, fluconazole and metronidazole. Seizure prophylaxis with lorazepam was given one day before BU exposure and continued until 1 day after completion.All three cases met modified JMML diagnostic criteria.

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Hematopoietic stem cell transplantation (HSCT) in children with juvenile myelomonocytic leukemia (JMML): results of the EWOG-MDS/EBMT trial

Cited by 290 publications

References 47 publications

Juvenile Myelomonocytic Leukemia in India: Cure Remains a Distant Dream!

Juvenile Myelomonocytic Leukemia in India: Cure Remains a Distant Dream!

Allogeneic hematopoietic SCT in children with ALL: current concepts of ongoing prospective SCT trials

Myeloablative BU, fludarabine, antithymocyte globulin and low-dose TBI in the treatment of juvenile myelomonocytic leukaemia with allogeneic haematopoietic cell transplantation

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