Retrospective Analysis of Single-Unit Umbilical Cord Blood Transplantation in Elderly Patients (Aged 65 Years and Older) with Predominantly High-Risk Myeloid Malignancies: A Single-Institution Study

Background

Myeloid malignancies in elderly patients often have poor prognostic chromosomal abnormalities and are characterized by increased risk of treatment-related mortality due to decreased physical capacity and comorbidities. Umbilical cord blood transplantation (UCBT) offers treatment flexibility due to easy availability and HLA compatibility. However, reports on the efficacy of UCBT in elderly patients are limited. This study evaluates the outcomes and utility of UCBT in elderly patients with myeloid malignancies.

Methods

We analyzed 231 patients aged 65 and older who underwent their first single-unit UCBT for myeloid malignancies at our institution from 2013 to 2023, excluding those with an ECOG PS of 4 at conditioning start. The primary endpoint was the 2-year overall survival (OS), with secondary endpoints including non-relapse mortality (NRM) and relapse rate. Kaplan-Meier method was used for OS and disease-free survival (DFS), and Gray's test for NRM, relapse rate, and neutrophil engraftment. Multivariate analysis employed the Cox proportional hazards model for OS and Fine-Gray proportional hazards regression for NRM and relapse rate.

Results

The median age was 68 years (range 65-80), with 77 patients aged 70 or older. The cohort included 155 males and 76 females. At transplantation, 175 patients had a KPS of 80-100, while 56 had less than 80. BMI was below 20 in 77 patients and 20 or above in 154 patients. HCT-CI scores were 0-2 in 163 patients and 3 or more in 68 patients. The underlying diseases were AML (n=195), MDS (n=33), and MPN (n=3), with 15 in CR and 216 in non-CR status. Refined Disease Risk Index (rDRI) showed 39 Intermediate, 131 High, and 61 Very High. Median TNC and CD34+ cell counts of cord blood were 2.4×10^7/kg and 0.84×10^5/kg, respectively. HLA-A, -B, -C, DRB1 allele mismatches were 0-2 in 96 patients and 3 or more in 135 patients. Conditioning regimens included MAC (n=143) and RIC (n=88), with TBI used in 72 patients. GVHD prophylaxis was Tac+MMF in 230 patients and Tac alone in 1 patient. The median follow-up period was 1199 days (190-4119 days). Neutrophil engraftment rate was 91.6% with a median of 20 days. The 2-year survival rate was 38.6%, 2-year DFS was 35.0%, 2-year NRM was 45.4%, and 2-year relapse rate was 20.0%. Survival improved over time (post-2018: 43.6% vs pre-2018: 31.6%, p=0.018), with no significant age difference (65-69 years: 37.9% vs ≥70 years: 40.3%, p=0.58). Cumulative incidence of acute GVHD was 56.3% (grade II-IV) and 20.3% (grade III-IV). Causes of death included relapse (n=36), infection (n=63), IPS+IP (n=22), GVHD (n=7), SOS (n=6), PTLD (n=2), secondary solid cancers (n=3), and others (n=20). Poor prognostic factors in multivariate analysis were KPS <80 (HR 2.05, p<0.001), transplantation before 2018 (HR 1.39, p=0.04), and BMI <20 (HR 1.49, p=0.023) for OS; HLA mismatch ≥3 alleles (HR 1.62, p=0.03), KPS <80 (HR 1.61, p=0.02), and transplantation before 2018 (HR 2.09, p<0.001) for NRM; and high/very high rDRI (HR 3.90, p=0.02) for RR.

Discussion

In our high-risk cohort, age did not significantly impact transplant outcomes. Although outcomes have improved over time, high NRM remains a concern. Matching HLA alleles within two alleles may reduce NRM. However, this approach shows a tendency towards higher relapse rates (HR 1.72, p=0.052), indicating the need for effective post-transplant maintenance therapies. Improving pre-transplant nutritional status and general condition is crucial for enhancing treatment outcomes. Further case accumulation is needed to support these observations.

Yamaguchi:AbbVie GK.: Honoraria; Nippon Shinyaku Co.: Honoraria. Kaji:Takeda Pharmaceutical Co.: Honoraria; Eisai Co.: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Genmab: Honoraria; AbbVie GK.: Honoraria; Asahi Kasei Pharma Co.: Honoraria; AstraZeneca: Honoraria; Bristol Myers Squibb K.K.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Meiji Seika Pharma Co.: Honoraria; Ono Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria; SymBio Pharmaceuticals: Honoraria. Takagi:MSD KK (Merck & Co. Inc.): Honoraria; Nippon Shinyaku Co.: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Kyowa Kirin Co.: Honoraria; Daiichi Sankyo Co.: Honoraria; GlaxoSmithKline KK.: Honoraria; AbbVie GK.: Honoraria; Amgen KK.: Honoraria; The Japanese Society of Hematology: Research Funding; Pfizer Japan Inc.: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Novartis Pharma Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Astellas Pharma Inc.: Honoraria; Asahi Kasei Pharma Co.: Honoraria; Sumitomo Pharma Co.: Honoraria; Okinaka Memorial Institute for Medical Research: Research Funding; Takeda Pharmaceutical Co.: Honoraria. Yamamoto:Astellas Pharma Inc.: Honoraria; MSD KK (Merck & Co.) Inc.: Honoraria; JCR Pharmaceuticals Co.,Ltd.: Honoraria; Janssen Pharmaceutical KK: Honoraria; Novartis Pharma Co.: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; CSL Behring K.K: Honoraria; AstraZeneca: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Takeda Pharmaceutical Co.: Honoraria; Asahi Kasei Pharma Co.: Honoraria; Sumitomo Pharma CO.,Ltd.: Honoraria. Yamamoto:Takeda Pharmaceutical Co.: Honoraria; Mundi Pharma Co.: Honoraria; Novartis Pharma Co.: Honoraria; Nihonkayaku Co.: Honoraria; Meiji Seika Pharma Co.: Honoraria; Bristol Myers Squibb K.K.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; AstraZeneca: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Genmab: Honoraria; Eisai Co.: Honoraria; Daiichi Sankyo Co.: Honoraria; Ono Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria. Wake:AbbVie GK: Honoraria; Alexionpharma: Honoraria; Amgen KK: Honoraria; Asahi Kasei Pharma Co.: Honoraria; Astellas Pharma Inc.: Honoraria; AstraZeneca: Honoraria; Bristol Myers Squibb K.K: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Daiichi Sankyo Co.: Honoraria; Eisai Co.: Honoraria; GlaxoSmithKline KK.: Honoraria; Janssen Pharmaceutical KK.: Honoraria; Kyowa Kirin Co.: Honoraria; Meiji Seika Pharma Co.: Honoraria; Mundi Pharma Co.: Honoraria; Nihonkayaku Co.: Honoraria; Novartis Pharma Co.: Honoraria; Ono Pharmaceutical Co.: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Pfizer Japan Inc.: Honoraria; Sanofi K.K.: Honoraria; SymBio Pharmaceuticals: Honoraria; Takeda Pharmaceutical Co.: Honoraria. Uchida:Astellas Pharma Inc.: Consultancy; Takeda Pharmaceutical Co.: Consultancy; Nippon Boehringer Ingelheim Co.: Research Funding; Sumitomo Pharma Co.: Research Funding; Chugai Pharmaceutical Co.: Research Funding; Fuji Pharma Co.: Research Funding; JCR Pharmaceuticals Co.: Research Funding; CSL Behring: Honoraria; MSD (Merck & Co. Inc.): Honoraria; Asahi Kasei Pharma Co.: Honoraria; Astellas Pharma Inc.: Honoraria; AstraZeneca: Honoraria; AbbVie GK: Honoraria; Otsuka Pharmaceutical Co.: Honoraria; Kyowa Kirin Co.: Honoraria; SymBio Pharmaceuticals: Honoraria; Daiichi Sankyo Co.: Honoraria; Takeda Pharmaceutical Co.: Honoraria; Chugai Pharmaceutical Co.: Honoraria; Nippon Shinyaku Co.: Honoraria; Novartis Pharma Co.: Honoraria.