Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

Sander, Annette; Zimmermann, Martin; Dworzak, Michael; Fleischhack, Gudrun; Neuhoff, Christine von; Reinhardt, Dirk; Kaspers, Gertjan J. L.; Creutzig, Ursula

doi:10.1038/leu.2010.127

Cited by 122 publications

(167 citation statements)

References 28 publications

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“…This fits to the good results after HSCT in CR1 in infants reported here and further indicates that acute toxicities can be better handled than in the past. 15 One problem in infants is the high rate of patients with CNS involvement, which may be due to the high frequency of monoblastic leukemias, as these cells are able to penetrate directly through the cytoplasm of the endothelial cells into the brain. 24 There is no satisfying treatment option, as cranial irradiation is associated with neurological late effects.…”

Section: Discussionmentioning

confidence: 99%

“…13 From October 2001, patients were enrolled in the international protocol relapsed AML-2001/01 with a randomized FLAG (fludarabine, cytarabine, granulocytecolony-stimulating factor) or FLAG/DNX (plus liposomal daunorubicin) induction. 14,15 There were no major changes in supportive-care strategies between the studies. The protocol guidelines recommend general prophylaxis for pneumocystis carinii pneumonia, and also to consider prophylaxis against viridans group streptococci and antifungal prophylaxis.…”

Section: Treatment Planmentioning

confidence: 99%

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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: Discussionmentioning

confidence: 99%

Section: Treatment Planmentioning

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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“…Five-year OS was 32%. 6 HSCT is currently considered to be the most promising therapeutic element in second remission (CR2). Germany has about 82 million inhabitants out of which 100 children are newly diagnosed with AML per year.…”

Section: Introductionmentioning

confidence: 99%

Allo-SCT using BU, CY and melphalan for children with AML in second CR

Beier

Albert

Bader

et al. 2012

Bone Marrow Transplant

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Based on the results from the AML-BFM 98 trial, hematopoietic SCT (HSCT) is recommended for children with AML in second CR only. Here, we retrospectively analyze interphase data of children who underwent HSCT after myeloablative conditioning with BU, CY, and melphalan (BuCyMel) for AML in second remission (CR2) between 1998 and 2009. Out of 152 children, transplant data were available on 109 individuals. Sixty out of 109 children (55%) received BuCyMel. Median age at HSCT was 12.2 years (range 3.0; 18.3). GVHD prophylaxis mostly consisted of CsA and short term MTX with or without antithymocyte globulin. Matched-sibling donors were used for 6/60 analyzed recipients, the remainder either received grafts from matched unrelated (30/60) or mismatched donors. OS after 5 years was 62% (s.e. 6%), relapse incidence 35% (18/60 children) and treatment-related mortality accounted for 12% (7/60) of fatal events. In conclusion, even taking into account possible selection bias in this retrospective analysis, HSCT in CR2 using BuCyMel resulted in a respectable OS. Based on this data the prospective, controlled and centrally monitored AML SCT-BFM 2007 trial has started to recruit patients in January 2010 aiming to generate valid outcome data for further strategy decisions.

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“…First, since standardization of therapy and testing new regimens on a common backbone was thought to be important to the improvement of disease control, by analogy, standardization of supportive care measures and testing of interventions with a common backbone of sup- portive care strategies may allow us to reduce infectious complications in a more rapid and more efficient manner. 7,8 Secondly, since restrictions may negatively affect the quality of life of children and their families, variability in supportive care measures may ultimately result in dissatisfaction of patients and lower compliance. 10 On the other hand, we may be able to describe comparative effectiveness of such practices if we could identify institutions that are otherwise similar with different practices although such an analysis would be highly susceptible to confounding variables.…”

Section: Number Of Centers Responding (% Of Total Centers)/ Number Ofmentioning

confidence: 99%

“…First, standardization of supportive care may result in improved outcomes. This has primarily been shown for disease treatment outcomes through standardization of cancer therapy and testing new regimens on a common backbone, 7,8 but has also been demonstrated for supportive measures. 9 Second, variability in management complicates care at an institutional level and may lead to dissatisfaction in patients if therapy changes as they move between different institutions.…”

Section: Introductionmentioning

confidence: 99%

Variations in non-pharmacological anti-infective measures in childhood leukemia - results of an international survey

et al. 2012

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The online version of this article has a Supplementary Appendix. BackgroundStandardization in clinical practice may lead to improved outcomes. Unfortunately, little is known about the variability of non-pharmacological anti-infective measures in children with cancer. Design and MethodsA web-based survey assessed institutional recommendations regarding restrictions of social contacts, pets and food and instructions on wearing face masks in public for children with standard-risk acute lymphoblastic leukemia and acute myeloid leukemia during intensive chemotherapy. ResultsA total of 336 institutions in 27 countries responded to the survey (range, 1-76 institutions per country; overall response rate 61%). Most institutions recommend that patients with acute myeloid leukemia avoid indoor public places and daycare, kindergarten and school, whereas recommendations for patients with acute lymphoblastic leukemia differ considerably by institution. In terms of restrictions related to pets, there was a wide variability between institutions for both acute lymphoblastic and acute myeloid leukemia patients. Most, but not all institutions do not allow children with either acute lymphoblastic or acute myeloid leukemia to eat raw meat, raw seafood or unpasteurized milk. Whereas most institutions do not routinely recommend that patients with acute lymphoblastic leukemia wear face masks in public, advice on this matter varies for patients with acute myeloid leukemia. ConclusionsThe survey demonstrates that there is a wide variation in recommendations on non-pharmacological anti-infective measures between different institutions, countries and continents. This information may be used to encourage harmonization of supportive care practices and future clinical trials.

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Consequent and intensified relapse therapy improved survival in pediatric AML: results of relapse treatment in 379 patients of three consecutive AML-BFM trials

Cited by 122 publications

References 28 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

Allo-SCT using BU, CY and melphalan for children with AML in second CR

Variations in non-pharmacological anti-infective measures in childhood leukemia - results of an international survey

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