Outcome of children with acute myeloid leukaemia (<scp>AML</scp>) experiencing primary induction failure in the <scp>AIEOP AML</scp> 2002/01 clinical trial

Quarello, Paola; Fagioli, Franca; Basso, Giuseppe; Putti, M. C.; Berger, Massimo; Luciani, Matteo; Rizzari, Carmelo; Menna, Giuseppe; Masetti, Riccardo; Locatelli, Franco

doi:10.1111/bjh.13611

Cited by 18 publications

(33 citation statements)

References 40 publications

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“…However, pediatric patients often present little comorbidity, and can afford heavy chemotherapies. Moreover, HSCT remains the only curative treatment for refractory AML 20 . The present data are in favor of the use of preventive defibrotide during HSCT procedure in patients who previously received more than 9 mg/m² of GO, consistent with previous studies showing that defibrotide reduces the severity of SOS 21 …”

Section: Discussionsupporting

confidence: 90%

Association of fludarabin, cytarabine, and fractioned gemtuzumab followed by hematopoietic stem cell transplantation for first‐line refractory acute myeloid leukemia in children: A single‐center experience

Penel‐Page

Pleşa

Girard

et al. 2020

Pediatric Blood & Cancer

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Context: Acute myeloid leukemia (AML) is a rare disease in children, with only 50% to 60% eventfree survival. Among patients with AML, 10% do not respond to first-line chemotherapy. There is no recommendation concerning second-line treatments. Gemtuzumab ozogamicin (GO) is a monoclonal antibody targeting CD33, linked to calicheamicin. We report the efficacy and tolerance of a salvage regimen of fludarabin, cytarabine, and GO (FLA-GO) in patients refractory to first-line treatment.Methods: Eight patients (median age 14.5 years), who had more than 2% minimal residual disease (MRD) by flow cytometry (MRD flow), received gemtuzumab 3 mg/m 2 on days 1, 4, 7, associated with cytarabine 2000 mg/m 2 and fludarabin 30 mg/m 2 on days 1 to 5.Results: Six patients achieved complete remission (CR) (blast count morphology ≤5 × 10 −2 , CR-MRD flow <1 × 10 −3 for four patients). Five patients received a second course. We observed 11 episodes of febrile neutropenia, including 6 septicemias without complication. There was no fungal infection or toxic death. Two patients received granulocyte colony stimulating factor.One patient had partial platelet recovery; one, prolonged pancytopenia. All patients received hematopoietic stem cell transplantation (HSCT). We observed five mild-to-severe sinusoidal obstruction syndromes during HSCT procedures, particularly in patients who did not receive defibrotide prophylaxis. At the date of last contact (median follow-up: 58 months; range: 22-78), six patients were in continuous CR with negative MRD. Two patients died of post-HSCT relapse. Conclusion:FLA-GO is a good salvage regimen for pediatric refractory AML, with significant but acceptable toxicity. HSCT is mandatory to achieve sustained CR in these patients.

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Section: Discussionsupporting

confidence: 90%

Association of fludarabin, cytarabine, and fractioned gemtuzumab followed by hematopoietic stem cell transplantation for first‐line refractory acute myeloid leukemia in children: A single‐center experience

Penel‐Page

Pleşa

Girard

et al. 2020

Pediatric Blood & Cancer

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“…Five to 10% of children with de novo AML and as many as 23% of patients with relapsed AML have a refractory disease, defined as failure to achieve a morphological remission after two courses of chemotherapy. [1][2][3][4] Since the incidence of AML in the pediatric population in the UK is 70 cases per year, between 8 and 12 children per year are expected to present with refractory AML in the country. Historically, the prognosis for this subgroup of patients has been dismal, with recent cooperative trials suggesting an overall survival (OS) of 22 and 14% for primary refractory and relapsed refractory pediatric AML.…”

Section: Introductionmentioning

confidence: 99%

“…Historically, the prognosis for this subgroup of patients has been dismal, with recent cooperative trials suggesting an overall survival (OS) of 22 and 14% for primary refractory and relapsed refractory pediatric AML. 3,4 The best treatment for these patients is yet to be identified. Allogeneic hematopoietic stem cell transplantation (SCT) represents the standard of care for high-risk frontline or relapsed AML.…”

Section: Introductionmentioning

confidence: 99%

Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience

O’Hare

Lucchini

Cummins

et al. 2017

Bone Marrow Transplant

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We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%. Relapse was the major cause of treatment failure and occurred in 32% of patients at a median of 61 days post SCT. Five-year overall survival and leukemia-free survival (LFS) were 43% (95% CI 31-61%). All patients with favorable cytogenetics (n=6) are alive in CR. Outcomes in patients with primary refractory disease were equivalent to those with relapsed refractory AML. Blast percentage ⩽30% in the BM pre-SCT, myeloablative conditioning and acute GVHD proved to be favorable prognostic features. We could stratify patients according to age ⩾10 years and >30% blasts in BM pre-SCT. Patients with none/one of these risk factors were highly salvageable (5 years LFS 53%) whereas those with both factors had a very poor prognosis (5 years LFS 10%). This may facilitate decision making on whether it is appropriate to consider transplant in such patients.

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“…The subsequent outcomes for a patient with induction failure are similar to the patient with AML who relapsed early (<12 months after remission) [60,61]. These patients, similar to patients that have relapsed, have been shown to have the highest end free survival after stem cell transplantation in comparison to after chemotherapy (31.2 vs. 5%, p < 0.0001) [62].…”

Section: Pediatric Aml Treatmentmentioning

confidence: 64%

Acute Myeloid Leukemia in Pediatric Patients: A Review About Current Diagnostic and Treatment Approaches

Derwich¹,

Mitkowski²,

J³

2018

Myeloid Leukemia

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Acute leukemia is the most common childhood malignancy, accounting for almost 35% of all childhood cancers. Acute myeloid leukemia (AML) represents 15-20% of pediatric acute leukemia. Majority of AML cases appear de novo, however a minority of cases can present as a secondary malignancy. AML is a highly heterogeneous disease and its diagnosis involves a combination of diagnostic analyses including morphology, immunophenotyping, cytochemistry, and leukemic blasts derived from peripheral blood or bone marrow demonstrating cytogenic and molecular characteristics. Through the identification of recurrent genetic mutations, it has been made possible to refine individual prognosis and guide therapeutic management. The current survival rate of children with AML is approximately 70%. The standard therapeutic regimen is a combination of cytarabine-and anthracycline-based regimens with allogenic stem cell transplantation in appropriate patients. Relapse in pediatric patients suffering from AML occurs in approximately 30% of cases, whereas death occurs in 5-10% of patients as a result of disease complications or chemotherapeutic side effects. In understanding the genetic basis of AML, targeted therapies will have the ability to reduce treatment-related morbidity and mortality. Here, we provide a comprehensive review of AML, its biology, diagnosis and therapeutic management in pediatric patients.

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Outcome of children with acute myeloid leukaemia (AML) experiencing primary induction failure in the AIEOP AML 2002/01 clinical trial

Cited by 18 publications

References 40 publications

Association of fludarabin, cytarabine, and fractioned gemtuzumab followed by hematopoietic stem cell transplantation for first‐line refractory acute myeloid leukemia in children: A single‐center experience

Association of fludarabin, cytarabine, and fractioned gemtuzumab followed by hematopoietic stem cell transplantation for first‐line refractory acute myeloid leukemia in children: A single‐center experience

Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience

Acute Myeloid Leukemia in Pediatric Patients: A Review About Current Diagnostic and Treatment Approaches

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