Adolescents and Young Adults with Acute Myeloid Leukemia Are Associated with Higher Treatment-Related Mortality and Inferior Overall Survival after Allogeneic Hematopoietic Cell Transplantation Compared with Children

Abstract BACKGROUND : There have been few reports on outcome of adolescent and young adults (AYAs) with acute myeloid leukemia (AML) who received allogeneic hematopoietic cell transplantation (allo-HCT). We performed a retrospective analysis of nationwide registration data of the Japan Society of Hematopoietic Cell Transplantation collected between 1990 and 2013 to assess the allo-HCT outcomes of AYA patients with AML in Japan. PATIENTS & METHODS : 2973 patients with de novo AML (excluding acute promyelocytic leukemia, myeloid leukemia associated with Down syndrome, and secondary AML) whose age was 0-29 years old at their first allo-HCT either in first or second remission (CR), primary induction failure, or first relapse were identified. Outcomes including overall survival rate (OS), disease-free survival rate (DFS), cumulative incidence of relapse (CIR), and treatment-related mortality (TRM) were compared between children (0-14 years old at HCT, N=1123) and AYAs (15-29 years old, N=1850). RESULTS : AYA patients had male predominance, higher incidence of intermediate risk cytogenetics but lower incidence of high-risk cytogenetics [-7/7q-, -5/5q-, complex karyotype, t(6;9), or t(16;21)], and higher prevalence of French-American-British M0, M1, and M2 morphology, while M5 and M7 were lower. Compared to children, AYA patients were transplanted more frequently by HLA-matched-related or unrelated donors, while less frequently by HLA-mismatched related or unrelated cord blood donors. As for conditioning regimen, proportion of myeloablative conditioning (MAC) using total-body-irradiation (TBI) was higher in the AYAs, while that of non-TBI MAC and reduced-intensity-conditioning (RIC) were lower. Cyclosporine was more frequently used than tacrolimus as graft-versus-host-disease (GVHD) prophylaxis in the AYAs. Five-year OS and DFS rates were significantly poorer in the AYAs: 58% vs 54% (p<0.01) and 53% vs 48% (p=0.03), respectively. Five-year CIR did not differ between the two groups; 33% vs 34% (p=0.99). However, 5-year TRM was significantly higher in the AYAs; 13% vs 16% (p=0.02). Multivariate analysis for both OS and TRM showed significant negative impact of AYAs, but not for DFS or CIR. Subgroup analyses showed that impact of AYAs for OS was greater in male, patients with low-risk cytogenetic abnormalities [t(8;21) or inv(16)], transplanted in CR, transplanted from HLA-matched related donor, received non-TBI MAC conditioning, or received cyclosporine-based GVHD prophylaxis. Finally, we analyzed the impact of transplant center types on HCT outcomes among the 317 adolescent patients (15-18 years old) who were transplanted at 1CR or 2CR, because they could be transplanted either by pediatricians or by adult hematologists according to their referral pattern. 92 cases were transplanted in pediatric centers, 203 in adult centers, and 22 in combined pediatric and adult centers. Basic characteristics and method of HCT did not differ significantly among the three groups. Interestingly, there was no difference in OS, DFS, CIR, or TRM. CONCLUSIONS : AYAs with AML showed inferior post-transplant survival, which was mainly due to higher TRM in the AYAs. Disclosures No relevant conflicts of interest to declare.

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Outcome of patients with acute myeloid leukemia with monosomal karyotype who undergo hematopoietic cell transplantation

Blood ◽

10.1182/blood-2011-02-339721 ◽

2011 ◽

Vol 118 (6) ◽

pp. 1490-1494 ◽

Cited By ~ 71

Author(s):

Min Fang ◽

Barry Storer ◽

Elihu Estey ◽

Megan Othus ◽

Lisa Zhang ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Cell Transplantation ◽

Myeloid Leukemia ◽

Hematopoietic Cell Transplantation ◽

Hazard Ratio ◽

Hematopoietic Cell ◽

Complex Karyotype ◽

Monosomal Karyotype ◽

Acute Myeloid

Abstract Monosomal karyotype (MK), defined as ≥ 2 autosomal monosomies or a single monosomy in the presence of other structural abnormalities, was confirmed by several studies to convey an extremely poor prognosis in patients with acute myeloid leukemia (AML) with a 4-year overall survival after diagnosis of < 4%. A recent investigation by the Southwest Oncology Group found that the only MK+ patients alive and disease free > 6 years from diagnosis received allogeneic hematopoietic cell transplantation (HCT). To expand this observation, we retrospectively analyzed 432 patients treated with HCT at the Fred Hutchinson Cancer Research Center, 14% of whom were MK+. The 4-year overall survival of patients after HCT was 25% for MK+ AML and 56% for MK− AML (adjusted hazard ratio = 2.29, P < .0001). Among the MK+ patients, complex karyotype was associated with a significantly worse outcome than patients with noncomplex karyotype (adjusted hazard ratio = 2.70, P = .03). Thus, although the prognosis of MK+ patients remains worse than that for MK− patients in the transplantation setting, HCT appears to improve the overall outcome of MK+ patients, especially patients without a complex karyotype. However, the 28% of MK+ patients > 60 years had only a 6% 4-year survival rate after HCT, stressing the need for new approaches in these patients.

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The Modified Pre-Transplant EBMT Risk Score Is Superior To The HCT-CI Score In Predicting Overall Survival and Non-Relapse Mortality After Allogeneic Hematopoietic Cell Transplantation In Patients With Acute Myeloid Leukemia

Blood ◽

10.1182/blood.v122.21.2153.2153 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2153-2153 ◽

Cited By ~ 2

Author(s):

Fotios V. Michelis ◽

Hans A. Messner ◽

Jieun Uhm ◽

Anna Lambie ◽

Laura McGillis ◽

...

Keyword(s):

Overall Survival ◽

Acute Myeloid Leukemia ◽

Prognostic Factor ◽

Cell Transplantation ◽

Myeloid Leukemia ◽

Hematopoietic Cell Transplantation ◽

Multivariable Analysis ◽

Hematopoietic Cell ◽

Significant Difference ◽

Acute Myeloid

Abstract A variety of factors have been investigated for their influence on outcomes post-allogeneic hematopoietic cell transplantation (HCT). Pre-HCT risk scores have been developed such as the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI) and the modified EBMT score (mEBMT) for acute leukemias (involving age, CR status, donor type and gender mismatch). The purpose of this single-center study was to investigate the influence of these scores on outcome post-HCT in 350 patients transplanted between 1999 and 2012 for acute myeloid leukemia (AML) and to compare the predictive value of these scores. Median age of all patients at transplant was 49 years (range 18-71 years), 174 patients (50%) were female. HCT was performed in first complete remission (CR1) for 245 patients (70%) and in second complete remission (CR2) for 105 patients (30%). Cytogenetics at diagnosis were available in 289 patients (83%). Donors were matched related (n=213, 61%) or matched unrelated (n=137, 39%). Cytomegalovirus (CMV) serostatus was negative for both donor and recipient in 113 patients (32%). Peripheral blood stem cells were used as a graft source in 272 patients (78%). Myeloablative conditioning was administered to 239 (68%) patients, 111 (32%) received reduced-intensity conditioning (RIC) regimens. The HCT-CI scores were grouped as 0, 1-2 and ≥3 (94, 137 and 119 patients respectively). The mEBMT scores were grouped as 0-1, 2, 3 and 4-5 (32, 134, 120 and 64 patients respectively). Median follow-up duration among survivors was 62 months (range 12-156 months). Univariate analysis demonstrated a significant difference of overall survival (OS) according to the HCT-CI score (p=0.03), 3-year OS 52%, 53% and 39% in HCT-CI score 0, 1-2 and ≥3 (Figure 1). The mEBMT score also demonstrated a significant difference of OS among the patients with scores 0-1, 2, 3 and 4-5 (p=0.002), 3-year OS 75%, 53%, 40% and 39% respectively (Figure 2). The HCT-CI and mEBMT scores could not stratify the patients according to the cumulative incidence of relapse (CIR) with p-value of 0.99 and 0.50 respectively. For cumulative incidence of non-relapse mortality (NRM), the HCT-CI showed a trend of statistical significance (p=0.07), while the mEBMT score could stratify the patients according to the risk of NRM (p=0.01). Multivariable analysis was performed including the HCT-CI and mEBMT scores as previously defined. Covariates already incorporated in the mEBMT score (age, CR status, related donors) were not included in the multivariable analysis. For OS, the HCT-CI score was removed from the final model due to statistical insignificance (p=0.17). However, the mEBMT score was confirmed as an independent prognostic variable for OS (p=0.00002, HR=1.5, 95%CI=1.2-1.8). For NRM, HCT-CI did not maintain significance (p=0.11) while mEBMT again was confirmed as an independent prognostic factor (p=0.0003, HR=1.5, 95%CI=1.2-1.9). The current study showed that the mEBMT score was confirmed as an independent prognostic factor for OS and NRM in patients with AML undergoing HCT, while the HCT-CI score was not confirmed. In conclusion, the mEBMT risk score is superior to the HCT-CI score in predicting OS and NRM following allogeneic HCT in AML patients. Disclosures: No relevant conflicts of interest to declare.

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