Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3 internal tandem duplication using the combination of induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases

Abstract

This content is licensed under a Creative Commons Attribution 4.0 International License.Successful treatment of post-transplant relapsed acute myeloid leukemia with FLT3 internal tandem duplication using the combination of induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Report of three cases ABSTRACTAcute myeloid leukemia is a hematopoietic stem cell neoplastic disease associated with high morbidity and mortality. The presence of FLT3 internal tandem duplication mutations leads to high rates of relapse and decreased overall survival. Patients with FLT3 internal tandem duplication are normally treated with hematopoietic stem cell transplantation in first complete remission. Nevertheless, the incidence of post-transplant relapse is considerable in this group of patients, and the management of this clinical condition is challenging. The report describes the outcomes of patients with FLT3 internal tandem duplication positive acute myeloid leukemia who relapsed after allogeneic hematopoietic stem cell transplantation and were treated with the combination of re-induction chemotherapy, donor lymphocyte infusion, sorafenib and azacitidine. Three cases are described and all patients achieved prolonged complete remission with the combined therapy. The combination of induction chemotherapy followed by donor lymphocyte infusion, and the maintenance with azacitidine and sorafenib can be effective approaches in the treatment of post-hematopoietic stem cell transplant and relapsed FLT3 internal tandem duplication positive acute myeloid leukemia patients. This strategy should be further explored in the context of clinical trials.

Feasibility, accuracy, and usability analysis of MapAML, a first‐in‐class app for integrated diagnosis in acute myeloid leukemia

“…The integration of multidisciplinary data, including clinical information, morphology, cytogenetics, immunophenotyping, and molecular data, is essential for an accurate diagnosis, risk stratification, and optimal therapy in AML. 5,15,16 In this study, we performed an analysis of the accuracy and usability of the smartphone application MapAML for integrated diagnosis in AML. Until the present moment, there is no similar tool that takes into account this wide range of clinical and laboratory information and produces an integrated AML diagnostic report.…”

“…The integration of multidisciplinary data, including clinical information, morphology, cytogenetics, immunophenotyping, and molecular data, is essential for an accurate diagnosis, risk stratification, and optimal therapy in AML 5,15,16 . In this study, we performed an analysis of the accuracy and usability of the smartphone application MapAML for integrated diagnosis in AML.…”

The role of FLT3 inhibitors as maintenance therapy following hematopoietic stem cell transplant

“… 6 patients were administered Sorafenib as relapse prophylaxis and 9 patients were administered Sorafenib at time of relapse Sorafenib max tolerated dose 200 mg BID. Median initial dosing 150 mg/m 2 qday (range 75 mg–340 mg/m 2 /day) 10/15 (67%) patients alive at median followup of 21 mo from start of Sorafenib 8/10 remain in CR with median survival 3.7years from HSCT - 4/8 in CR from Sorafenib prophylaxis group 7/15 PD or recurrent disease on Sorafenib 11/15 experienced medically significant toxicities including myelosuppression ( n = 3), thrombocytopenia ( n = 3), GI upset ( n = 2), rash ( n = 4), infection ( n = 2), transaminitis ( n = 2), cardiac dysfunction ( n = 2), palmar plantar erythrodesia ( n = 2) Salem et al [70] Retrospective study 10 patients (30–65yo) with FLT-ITD + and NPM1 + AML treated with Sorafenib maintenance post-alloHSCT 10patients proceeded to alloHSCT (7MRD, 3HID) and received Sorafenib as post-alloHSCT maintenance therapy Sorafenib started median 55d post-alloHSCT Sorafenib initial dose 400 mg BID and dose adjusted per side effects At median 12.5 mo post-alloHSCT follow-up, 9/10 patients CMR, MRD neg for both FLT3 and NPM1 1/10 patient died from severe, refractory liver GvHD 7mo post alloHSCT Rash, hematologic toxicity 3/10 patients developed acute GVHD before sorafenib Campregher et al [71] Case series 3 patients with FLT3-ITD + AML relapsed post-alloHSCT treated with combination chemotherapy, DLI, Sorafenib and azacitidine Patient 1: relapsed day +54, treated with fludarabine, cytarabine followed by DLI with Sorafenib and Azacitidine beginning 1 mo post DLI Patient 2: relapse 1 year, treated with HIDAC followed by DLI with Sorafenib and Azacitidine after count recovery from HIDAC Patient 3: relapse day + 84, treated with FLAG then FLAMSA MEL followed by DLI and azacitidine. Sorafenib started 3 mo later but discontinued due to AE.…”

A Unique Case of Durable Complete Remission after Salvage with Azacitidine and DLI for High Risk FLT-3 Positive Acute Myeloid Leukemia, Following Relapse 18 Months Post Allogeneic Stem Cell Transplant

“…7-10 Despite this, recent case reports have suggested that the FLT3 inhibitor sorafenib, used in combination with azacitadine and donor lymphocyte infusions in patients with FLT3-itd mutated AML, who have relapsed post-transplant, can be an effective approach that warrants further evaluation in clinical trials. 11…”