Allogeneic hematopoietic cell transplantation in patients with AML not achieving remission: potentially curative therapy

Gyurkocza, Boglarka; Lazarus, Hillard M.; Giralt, Sergío

doi:10.1038/bmt.2017.8

Cited by 38 publications

(21 citation statements)

References 57 publications

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“…Several studies have shown that APMF is associated with poor response to chemotherapy, and median survival time is usually less than 1 year [2][3][4][5]. Because allogeneic HCTs have curative potential for relapsed, refractory, and poor prognostic myeloid malignancies [19], HCT has been attempted to treat APMF. Although a limited number of APMF cases treated with HCT have been reported [8][9][10][11][12], the outcome of HCT in patients with APMF has never been systematically studied.…”

Section: Discussionmentioning

confidence: 99%

Hematopoietic Cell Transplantation for Acute Panmyelosis with Myelofibrosis: A Retrospective Study in Japan

Konuma

Kondo

Kawata

et al. 2019

Biology of Blood and Marrow Transplantation

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Acute panmyelosis with myelofibrosis (APMF) is a rare subtype of acute myeloid leukemia characterized by acute onset of cytopenias and bone marrow fibrosis in the absence of splenomegaly. Because the prognosis of APMF is extremely poor even after chemotherapy, hematopoietic cell transplantation (HCT) has been used to treat APMF. However, the outcome after HCT for APMF remains unclear. To evaluate the outcomes and prognostic factors after HCT as a therapeutic modality for APMF, we retrospectively analyzed the Japanese registration data of 40 APMF patients who received allogeneic and syngeneic HCT between 2005 and 2015. The median age at HCT was 53.5years (range, 16 to 70). The disease status at HCT was first complete remission (CR1) in 13 patients (33%). The probability of overall survival and the cumulative incidence of relapse at 3years were 24% and 59%, respectively. Univariate analysis identified that female sex and disease status CR1 at the time of HCT were significantly associated with higher overall survival. Although APMF patients have a poor long-term prognosis even after syngeneic and allogeneic HCT, these data suggested that allogeneic HCT offered a curative option for APMF.

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Section: Discussionmentioning

confidence: 99%

Hematopoietic Cell Transplantation for Acute Panmyelosis with Myelofibrosis: A Retrospective Study in Japan

Konuma

Kondo

Kawata

et al. 2019

Biology of Blood and Marrow Transplantation

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“…Pursuing stem cell transplantation depends on the fitness and age of the patient, risk of relapse after having achieved a CR, availability of a donor, access to a transplant center, and financial eligibility. Patients with higher risk features such as poor‐risk cytogenetics or adverse mutations, patients with therapy‐related AML, patients who fail to obtain a CR after induction (primary induction failure), or patients with relapsed refractory disease may be appropriate candidates for transplantation . The use of alternative stem cell sources (haploidentical donors, umbilical cord blood, and matched unrelated donors) and reduced intensity and nonmyeloablative conditioning regimens have expanded the eligibility for transplantation .…”

Section: Treatment Of Acute Myeloid Leukemiamentioning

confidence: 99%

“…15 The use of alternative stem cell sources (haploidentical donors, umbilical cord blood, and matched unrelated donors) and reduced intensity and nonmyeloablative conditioning regimens have expanded the eligibility for transplantation. 15 A donor search should be initiated in patients with any nonfavorable risk while the patient is undergoing induction chemotherapy. 8 Although no standard maintenance treatment exists, maintenance may be used after postremission chemotherapy or posttransplantation in certain patients who are at a high risk of relapse (such as those who are FLT3-positive and/or who have detectable residual disease after transplantation), and may consist of tyrosine kinase inhibitors (TKIs), hypomethylating agents, and/or prophylactic donor lymphocyte infusions (in posttransplantation patients only).…”

Section: Standard Aml Treatmentmentioning

confidence: 99%

Midostaurin: A New Oral Agent Targeting FMS‐Like Tyrosine Kinase 3‐Mutant Acute Myeloid Leukemia

Stansfield

Pollyea

2017

Pharmacotherapy

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Acute myeloid leukemia (AML), a clonal hematologic malignancy that results in bone marrow failure, is the most common acute leukemia in adults (median age of diagnosis 67 yrs), and treatment options, especially in the elderly population, are limited. Induction chemotherapy with 7 + 3, the combination of continuous-infusion cytarabine and intermittent dosing of an anthracycline administered over 7 and 3 days, respectively, has remained the standard of care since its introduction in 1973 in the United States. Midostaurin is a first-generation FMS-like tyrosine kinase 3 (FLT3) inhibitor (TKI) that was approved by the U.S. Food and Drug Administration in April 2017 for the treatment of FLT3-mutant AML. We performed a search of the PubMed database (January 1990-January 2017) to review pertinent clinical trials of midostaurin. Phase I, II, and III trials reported in English evaluating the safety and efficacy of midostaurin in patients with AML or myelodysplastic syndrome were included. The ClinicalTrials.gov database was also searched for ongoing trials. In the only phase III trial that has been conducted to date, midostaurin demonstrated significant improvement compared with placebo in overall and event-free survival in patients aged 18-59 years with newly diagnosed FLT3-mutant AML treated with standard induction chemotherapy. The median overall survival for patients randomized to the midostaurin group was 74.7 months versus 25.6 months in the placebo group (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.63-0.96, p=0.009). Median event-free survival was 8.2 months with midostaurin compared with 3.0 months with placebo (HR 0.78, 95% CI 0.66-0.93, p=0.002). In addition to being evaluated in combination with conventional chemotherapy, midostaurin has been studied as monotherapy, in combination with the hypomethylating agents azacitidine and decitabine, and as single-agent maintenance. Studies evaluating midostaurin in the maintenance setting after allogeneic stem cell transplantation are underway. Midostaurin is the first oral multitargeted TKI to improve overall survival in patients with FLT3-mutant AML and represents an important addition to the limited armamentarium against AML.

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“…Allogeneic hematopoietic cell transplantation (HCT) is the only potential curative therapy for patients with nonremission myeloid malignancies [1][2][3]. Cord blood transplantation (CBT) is an acceptable alternative donor source for patients without HLA-matched related or unrelated donors in need of allogeneic HCT [4][5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Reduced-Toxicity Myeloablative Conditioning Consisting of Fludarabine/Busulfan/Low-Dose Total Body Irradiation/Granulocyte Colony-Stimulating Factor–Combined Cytarabine in Single Cord Blood Transplantation for Elderly Patients with Nonremission Myeloid Malignancies

Konuma

Kato

Isobe

et al. 2019

Biology of Blood and Marrow Transplantation

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A B S T R A C TThe optimal intensity of a conditioning regimen might be dependent on not only age and comorbidities but also disease activity and the type of graft source. We evaluated the outcome of unrelated single cord blood transplantation (CBT) using a conditioning regimen of fludarabine 180 mg/m 2 , i.v. busulfan 9.6 mg/kg, 4 Gy total body irradiation, granulocyte colony-stimulating factorÀcombined high-dose cytarabine (12 g/m 2 ) in 23 elderly patients (median, 64 years) with nonremission myeloid malignancies between 2013 and 2018 in our institution. All but 1 patient achieved neutrophil engraftment at a median of 23.5 days (range, 18 to 50). With a median follow-up of 28 months, the probabilities of overall survival (OS), disease-free survival (DFS), and cumulative incidence of relapse at 2 years were 62%, 52%, and 26%, respectively. The cumulative incidences of nonrelapse mortality at 100 days and 2 years were 9% and 22%, respectively. In the univariable analysis a higher proportion of blasts in bone marrow and in peripheral blood and a monosomal or complex karyotype were significantly associated with inferior OS and DFS. Poor cytogenetics were significantly associated with inferior DFS and increased relapse incidence. These data demonstrate that this reduced-toxicity myeloablative conditioning regimen was tolerable and effective in terms of engraftment, relapse, and survival in single CBT for elderly patients with nonremission myeloid malignancies.

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Allogeneic hematopoietic cell transplantation in patients with AML not achieving remission: potentially curative therapy

Cited by 38 publications

References 57 publications

Hematopoietic Cell Transplantation for Acute Panmyelosis with Myelofibrosis: A Retrospective Study in Japan

Hematopoietic Cell Transplantation for Acute Panmyelosis with Myelofibrosis: A Retrospective Study in Japan

Midostaurin: A New Oral Agent Targeting FMS‐Like Tyrosine Kinase 3‐Mutant Acute Myeloid Leukemia

Reduced-Toxicity Myeloablative Conditioning Consisting of Fludarabine/Busulfan/Low-Dose Total Body Irradiation/Granulocyte Colony-Stimulating Factor–Combined Cytarabine in Single Cord Blood Transplantation for Elderly Patients with Nonremission Myeloid Malignancies

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