Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia

Sanders, Jean E.; Im, Ho Joon; Hoffmeister, Paul A.; Gooley, Ted; Woolfrey, Ann E.; Carpenter, Paul A.; Andrews, Robert G.; Bryant, Eileen; Appelbaum, Frederick R.

doi:10.1182/blood-2004-08-3312

Cited by 79 publications

(73 citation statements)

References 44 publications

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“…Very young children are considered particularly vulnerable patients who may not tolerate intensive treatment and hold a high risk for long-term sequelae after intensive chemotherapy, cranial irradiation and even more after hematopoietic stem cell transplantation (HSCT). 4 Whereas it is well known that infants with ALL have worse outcome than older children, 5 it was suggested that this might not be the case in AML. 6,7 During the past decade, prognosis improved not only in standardrisk (SR) but also in HR pediatric AML.…”

Section: Introductionmentioning

confidence: 99%

Favorable outcome in infants with AML after intensive first- and second-line treatment: an AML-BFM study group report

et al. 2011

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Infants o1 year of age have a high prevalence of prognostically unfavorable leukemias and a presumed susceptibility to treatment-related toxicities. A total of 125 infants with acute myeloid leukemia (AML) were treated in studies AML-BFM-98 (n ¼ 59) and -2004 (n ¼ 66). Treatment regimens of both studies were comparable, consisting of intensive induction followed by four courses (mainly high-dose cytarabine and anthracyclines). Allogeneic-hematopoietic stem-cell-transplantation (allo-HSCT) in 1st remission was optional for high-risk (HR) patients. Most infants (120/125 ¼ 96%) were HR patients according to morphological, cytogenetic/molecular genetic and response criteria. Five-year overall survival was 66±4%, and improved from 61±6% in study-98 to 75±6% in study-2004 (P logrank 0.14) and event-free survival rates were 44±6% and 51±6% (P logrank 0.66), respectively. Results in HR infants were similar to those of older HR children (1-o2-or 2-o10-year olds, P logrank 0.90 for survival). Survival rates of HSCT in 1st remission, initial partial response and after relapse were high (13/14, 2/8 and 20/30 patients, respectively). The latter contributes to excellent 5-year survival after relapse (50±8%). Despite more severe infections and pulmonary toxicities in infants, treatment-related death rate was identical to that of older children (3%). Our data indicate that intensive frontline and relapse AML treatment is feasible in infants, toxicities are manageable, and outcome is favorable.

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Section: Introductionmentioning

confidence: 99%

Favorable outcome in infants with AML after intensive first- and second-line treatment: an AML-BFM study group report

et al. 2011

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“…9 We recognise that the use of TBI in our approach can be challenged and that some of the toxicities observed may be attributed to the addition of this low-dose irradiation to the conditioning regimen, although doses of 1200 cGy for infants with ALL have been shown to be tolerable, albeit in a recipient with likely different comorbidities. 12 In summary, these data suggest that our conditioning regimen is feasible in the treatment of JMML. Such conditioning, although potentially curative, still carries notable risks for children with this disease.…”

mentioning

confidence: 95%

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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“…Unfortunately, EFS is poor for infants transplanted after relapse, and it is unlikely to improve especially for patients coming for SCT after extremely aggressive primary chemotherapy. 10,11 Children with either B-cell or T-cell ALL and specific highrisk features, for example, marked leukocytosis at presentation, hypodiploid karyotype, inadequate response to induction chemotherapy or persistent minimal residual disease, have experienced a high failure rate on contemporary chemotherapy regimens. 3 If an HLA-matched related donor is available, SCT in first remission may be a more effective approach for these very high-risk subsets.…”

Section: Sct In First Remissionmentioning

confidence: 99%

“…9 Results following SCT, from both related and unrelated donors, find that for infants in first remission, EFS ranges between 64 and 76%. [10][11][12] These infants underwent fully ablative conditioning, many receiving TBI, which increases the concern for late effects on growth and neurocognitive development. Although the risk of relapse with chemotherapy is high, it may be proposed to limit SCT to just those infants who relapse.…”

Section: Sct In First Remissionmentioning

confidence: 99%

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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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Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia

Cited by 79 publications

References 44 publications

Favorable outcome in infants with AML after intensive first- and second-line treatment: an AML-BFM study group report

Favorable outcome in infants with AML after intensive first- and second-line treatment: an AML-BFM study group report

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

Transplantation for children with acute lymphoblastic leukemia

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