Cytogenetics and outcome of allogeneic transplantation in first remission of acute myeloid leukemia: the French pediatric experience

Abstract Patients with acute myeloid leukemia who harbor an FMS-like tyrosine kinase 3 (FLT3) mutation present several dilemmas for the clinician. The results of an FLT3 mutation test, which can be influenced by several variables, need to be interpreted according to the clinical setting and there is a need for internationally standardized FLT3 mutation assays. Because of the lack of prospective studies, the role of allogeneic transplantation as consolidation therapy is still somewhat controversial, but the preponderance of evidence suggests that transplantation in first remission, if possible, is probably the best option. Clinically useful FLT3 inhibitors are hopefully on the near horizon and are being studied in the context of current treatment paradigms.

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No Impact of Postremission Consolidation Chemotherapy Before Allogeneic Transplant in Patients with First Remission Acute Myeloid Leukemia with Intermediate or High Risk Cytogenetics.

Blood ◽

10.1182/blood.v112.11.2164.2164 ◽

2008 ◽

Vol 112 (11) ◽

pp. 2164-2164

Author(s):

Lisa O. Sproat ◽

Brian Bolwell ◽

Lisa Rybicki ◽

Matt Kalaycio ◽

Robert Dean ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

High Risk ◽

Myeloid Leukemia ◽

Allogeneic Transplantation ◽

Intermediate Risk ◽

Allogeneic Transplant ◽

Consolidation Chemotherapy ◽

P Values ◽

First Remission ◽

Acute Myeloid

Abstract Despite a lack of evidence that postremission consolidation chemotherapy improves outcome of allogeneic transplantation in patients with acute myeloid leukemia (AML) in first remission, high dose cytarabine and other regimens are commonly administered to these patients. We studied a consecutive cohort of 73 adult patients with AML at high risk of relapse by published criteria who underwent allogeneic transplantation in first remision to determine whether specific patient and treatment characteristics identified subgroups of patients who might benefit from consolidation therapy prior to allogeneic transplantation. Pretransplant cytogenetics were available for 56 patients. Transplantation occurred between 1988 and 2008. The primary analysis grouped patients according to cytogenetic risk (poor versus intermediate) and consolidation chemotherapy (yes versus no). Consolidation Chemotherapy No Consolidation Chemotherapy None of the measured outcomes (relapse mortality (RM), non-relapse mortality (NRM), overall survival (OS)) differed significantly between groups. Poor Risk Cytogenetics 9 13 Intermediate Risk 18 16 Cytogenetics P Values for Consolidation Versus No Consolidation by Cytogenetic Risk Poor Risk Cytogenetics Intermediate Risk Cytogenetics When cytogenetic risk was not stratified the results between consolidation and no consolidation were also not significant. RM 0.95 0.74 NRM 0.73 0.19 OS 0.77 0.21 P Values for Consolidation Versus No Consolidation RM 0.70 NRM 0.12 OS 0.14 Neither this study nor others provide evidence that consolidation chemotherapy is beneficial to all patients with AML in first remission who undergo allogeneic transplant or to cytogenetic subgroups. Delays in referral to a transplant center, in tissue typing or physician preference to administer consolidation chemotherapy are not justified and expose patients to the inconvenience, risk, and cost of unnecessary treatment. Clinicians should avoid consolidation chemotherapy and expedite allogeneic transplantion in patients with AML in first remission in whom transplantation is the preferred treatment.

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Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

Blood ◽

10.1182/blood.v74.5.1507.1507 ◽

1989 ◽

Vol 74 (5) ◽

pp. 1507-1516 ◽

Cited By ~ 42

Author(s):

DW Beelen ◽

K Quabeck ◽

U Graeven ◽

HG Sayer ◽

HK Mahmoud ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Marrow Transplantation ◽

Myeloid Leukemia ◽

Allogeneic Transplantation ◽

Cytotoxic Agents ◽

High Dose ◽

Skin Reactions ◽

Preparative Regimen ◽

First Remission ◽

Acute Myeloid

Abstract The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).

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Acute toxicity and first clinical results of intensive postinduction therapy using a modified busulfan and cyclophosphamide regimen with autologous bone marrow rescue in first remission of acute myeloid leukemia [see comments]

Blood ◽

10.1182/blood.v74.5.1507.bloodjournal7451507 ◽

1989 ◽

Vol 74 (5) ◽

pp. 1507-1516

Author(s):

DW Beelen ◽

K Quabeck ◽

U Graeven ◽

HG Sayer ◽

HK Mahmoud ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Marrow Transplantation ◽

Myeloid Leukemia ◽

Allogeneic Transplantation ◽

Cytotoxic Agents ◽

High Dose ◽

Skin Reactions ◽

Preparative Regimen ◽

First Remission ◽

Acute Myeloid

The combination of high-dose busulfan (16 mg/kg) and 200 mg/kg cyclophosphamide is gaining increasing significance as a preparative regimen prior to autologous, syngeneic, or allogeneic marrow transplantation. A new regimen of high-dose busulfan in conjunction with a reduced dose of 120 mg/kg cyclophosphamide has recently been described as a preparative regimen prior to allogeneic transplantation. To determine the drug-related nonhematologic toxic effects of this new regimen without confounding factors associated with allogeneic transplantation, we conducted a pilot study using this new regimen in 20 patients with acute myeloid leukemia (AML) in first remission prior to autologous unpurged marrow transplantation. All patients experienced transient non-life-threatening acute drug-related toxicity with skin reactions in 20 (100%), nausea and vomiting in 20 (100%), oral mucositis in 18 (90%), hepatic functional impairment in 17 (85%), hemorrhagic cystitis in three (15%), and generalized seizures in two (10%) of these patients, respectively. Two procedural, fatal complications resulted from infectious causes that were not directly related to the speed of hematopoietic reconstitution or the toxicity of the preparative regimen. The 3-year event-free survival estimate (55% +/- 11%) and probability of leukemic recurrence (38% +/- 11%) attained with this new regimen in recipients of autografts in first remission of AML are promising and challenge comparisons with preparative regimens employing combinations of cytotoxic agents or total body irradiation (TBI).

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Impact of FLT3ITD mutant allele level on relapse risk in intermediate-risk acute myeloid leukemia

Blood ◽

10.1182/blood-2014-02-554667 ◽

2014 ◽

Vol 124 (2) ◽

pp. 273-276 ◽

Cited By ~ 63

Author(s):

David C. Linch ◽

Robert K. Hills ◽

Alan K. Burnett ◽

Asim Khwaja ◽

Rosemary E. Gale

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

Mutant Allele ◽

Allogeneic Transplantation ◽

Intermediate Risk ◽

Relapse Risk ◽

Key Points ◽

First Remission ◽

Good Risk ◽

Acute Myeloid

Key Points In cases with intermediate-risk NPM1MUT AML, there are only minor differences in relapse risk according to FLT3ITD level. When considering allogeneic transplantation in first remission, NPM1MUT cases with low-level FLT3ITD should not be considered as good risk.

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Allogeneic hematopoietic stem cell transplantation for intermediate-risk acute myeloid leukemia in the first remission: outcomes using haploidentical donors are similar to those using matched siblings

Annals of Hematology ◽

10.1007/s00277-020-04359-x ◽

2021 ◽

Author(s):

Yan-Ru Ma ◽

Lan-Ping Xu ◽

Xiao-Hui Zhang ◽

Kai-Yan Liu ◽

Ying-Jun Chang ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Myeloid Leukemia ◽

Intermediate Risk ◽

Hematopoietic Stem ◽

First Remission ◽

Acute Myeloid

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Randomized Phase II Study of Clofarabine-Based Consolidation for Younger Adults With Acute Myeloid Leukemia in First Remission

Journal of Clinical Oncology ◽

10.1200/jco.2016.70.4551 ◽

2017 ◽

Vol 35 (11) ◽

pp. 1223-1230 ◽

Cited By ~ 17

Author(s):

Xavier Thomas ◽

Stéphane de Botton ◽

Sylvie Chevret ◽

Denis Caillot ◽

Emmanuel Raffoux ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

High Dose ◽

Younger Patients ◽

Hazard Ratios ◽

Randomized Phase Ii ◽

Nonhematologic Toxicity ◽

Donor Identification ◽

First Remission ◽

Acute Myeloid

Purpose To evaluate the efficacy and safety of a clofarabine-based combination (CLARA) versus conventional high-dose cytarabine (HDAC) as postremission chemotherapy in younger patients with acute myeloid leukemia (AML). Patients and Methods Patients age 18 to 59 years old with intermediate- or unfavorable-risk AML in first remission and no identified donor for allogeneic stem-cell transplantation (SCT) were eligible. Two hundred twenty-one patients were randomly assigned to receive three CLARA or three HDAC consolidation cycles. The primary end point was relapse-free survival (RFS). To handle the confounding effect of SCT that could occur in patients with late donor identification, hazard ratios (HRs) of events were adjusted on the time-dependent treatment × SCT interaction term. Results At 2 years, RFS was 58.5% (95% CI, 49% to 67%) in the CLARA arm and 46.5% (95% CI, 37% to 55%) in the HDAC arm. Overall, 110 patients (55 in each arm) received SCT in first remission. On the basis of a multivariable Cox-adjusted treatment × SCT interaction, the HR of CLARA over HDAC before or in absence of SCT was 0.65 (95% CI, 0.43 to 0.98; P = .041). In a sensitivity analysis, when patients who received SCT in first remission were censored at SCT time, 2-year RFS was 53.3% (95% CI, 39% to 66%) in the CLARA arm and 31.0% (95% CI, 19% to 43%) in the HDAC arm (HR, 0.63; 95% CI, 0.41 to 0.98; P = .043). Gain in RFS could be related to the lower cumulative incidence of relapse observed in the CLARA arm versus the HDAC arm (33.9% v 46.4% at 2 years, respectively; cause-specific HR, 0.61; 95% CI, 0.40 to 0.94; P = .025). CLARA cycles were associated with higher hematologic and nonhematologic toxicity than HDAC cycles. Conclusion These results suggest that CLARA might be considered as a new chemotherapy option in younger patients with AML in first remission.

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