High-risk patients

A retrospective analysis from the COG and CIBMTR compared chemotherapy only with matched-related donor and matched-unrelated donor HSCT for patients with AML and high-risk cytogenetics, defined as monosomy 7/del(7q), monosomy 5/del(5q), abnormalities of 3q, t(6;9), or complex karyotypes.[79]

A retrospective analysis from the COG and CIBMTR compared chemotherapy only with matched-related donor and matched-unrelated donor HSCT for patients with AML and high-risk cytogenetics, defined as monosomy 7/del(7q), monosomy 5/del(5q), abnormalities of 3q, t(6;9), or complex karyotypes.[79]

The analysis demonstrated no difference in the 5-year OS among the three treatment groups.

A Nordic Society for Pediatric Hematology and Oncology (NOPHO) study evaluated time-intensive reinduction therapy followed by transplant with best available donor for patients whose AML did not respond to induction therapy.[80][Level of evidence B4]

A Nordic Society for Pediatric Hematology and Oncology (NOPHO) study evaluated time-intensive reinduction therapy followed by transplant with best available donor for patients whose AML did not respond to induction therapy.[80][Level of evidence B4]

This treatment resulted in a 70% survival rate at a median follow-up of 2.6 years.

The subsequent risk-stratified NOPHO-DBH-AML2012 (NCT01828489) study reported the following:[81]

The subsequent risk-stratified NOPHO-DBH-AML2012 (NCT01828489) study reported the following:[81]

The 5-year EFS rate was 74.1% for patients with high-risk AML defined by flow cytometry MRD of >0.1% on day 22 of induction 1 (or any MRD for patients with FLT3 ITD), 85% of whom received HSCT in first CR. This outcome compared favorably with the 5-year EFS rate of 67.1% for patients with non–high-risk AML who received four to five courses of chemotherapy.

A single-institution retrospective study included 36 consecutive patients (aged 0–30 years) with high-risk AML (FLT3 ITD, 11q23 KMT2A rearrangements, presence of chromosome 5 or 7 abnormalities, induction failure, persistent disease), who were in a morphological first remission before allogeneic transplant.[82]

A single-institution retrospective study included 36 consecutive patients (aged 0–30 years) with high-risk AML (FLT3 ITD, 11q23 KMT2A rearrangements, presence of chromosome 5 or 7 abnormalities, induction failure, persistent disease), who were in a morphological first remission before allogeneic transplant.[82]

The investigators reported a 5-year OS rate of 72% and a LFS rate (from the time of transplant) of 69% with the use of a myeloablative conditioning regimen.

A single-institution retrospective study included 36 consecutive patients (aged 0–30 years) with high-risk AML (FLT3 ITD, 11q23 KMT2A rearrangements, presence of chromosome 5 or 7 abnormalities, induction failure, persistent disease), who were in a morphological first remission before allogeneic transplant.[82]

They also reported a treatment-related mortality rate of 17%.

A single-institution retrospective study included 36 consecutive patients (aged 0–30 years) with high-risk AML (FLT3 ITD, 11q23 KMT2A rearrangements, presence of chromosome 5 or 7 abnormalities, induction failure, persistent disease), who were in a morphological first remission before allogeneic transplant.[82]

These outcomes were similar to 14 patients with standard-risk AML who underwent transplant during the same time period.

A subgroup analysis from the AML-BFM 98 clinical trial demonstrated improved survival rates for patients with 11q23 aberrations allocated to allogeneic HSCT, but not for patients without 11q23 aberrations.[71]

For children with FLT3 ITD (high-allelic ratio), patients who received matched family donor HSCT (n = 6) had higher OS rates than those who received standard chemotherapy (n = 28). However, the number of cases studied limited the ability to draw conclusions.[83]

A subsequent retrospective report from three consecutive trials in young adults with AML found that patients with FLT3 ITD high-allelic ratio benefited from allogeneic HSCT (P = .03), but patients with low-allelic ratio did not (P = .64).[84]

A subset analysis of a COG phase III trial evaluated gemtuzumab ozogamicin during induction therapy in children with newly diagnosed AML.[21]

A subset analysis of a COG phase III trial evaluated gemtuzumab ozogamicin during induction therapy in children with newly diagnosed AML.[21]

For patients with FLT3 ITD high-allelic ratio who received HSCT, a lower relapse rate was observed for those who also received gemtuzumab ozogamicin (15% vs. 53%, P = .007).

A subset analysis of a COG phase III trial evaluated gemtuzumab ozogamicin during induction therapy in children with newly diagnosed AML.[21]

Conversely, patients who received gemtuzumab ozogamicin had higher rates of treatment-related mortality (19% vs. 7%, P = .08), resulting in overall improved DFS (65% vs. 40%, P = .08).