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.

Abstract

CONTEXT:

Acute myeloid leukemia (AML) is a rare disease in children, with only 50% to 60% event-free 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/m² on days 1, 4, 7, associated with cytarabine 2000 mg/m² and fludarabin 30 mg/m² 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.

• Authors: Mathilde Penel-Page, Adriana Plesa, Sandrine Girard, Alice Marceau-Renaut, Cécile Renard, Yves Bertrand
• Journal: Pediatric blood & cancer (Pediatr Blood Cancer) Vol. 67 Issue 6 Pg. e28305 (06 2020) ISSN: 1545-5017 [Electronic] United States
• PMID: 32307866 (Publication Type: Clinical Trial, Journal Article)
• Copyright: © 2020 Wiley Periodicals, Inc.

Chemical References

• Cytarabine
• Gemtuzumab
• Vidarabine
• fludarabine

Topics

• Adolescent
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Child
• Combined Modality Therapy
• Cytarabine (administration & dosage)
• Drug Resistance, Neoplasm
• Female
• Follow-Up Studies
• Gemtuzumab (administration & dosage)
• Hematopoietic Stem Cell Transplantation (mortality)
• Humans
• Leukemia, Myeloid, Acute (pathology, therapy)
• Male
• Neoplasm Recurrence, Local (pathology, therapy)
• Prognosis
• Retrospective Studies
• Salvage Therapy
• Survival Rate
• Vidarabine (administration & dosage, analogs & derivatives)