scholarly journals Decision Analysis of Donor Selection in Allogeneic Stem Cell Transplantation for Patients with Acute Leukemia in First Remission-Related Donor with HLA-1 Antigen Mismatch in the GVH Direction vs. HLA-8/8 Allele-Matched Unrelated Donor

2013 ◽  
Vol 19 (2) ◽  
pp. S346-S347 ◽  
Author(s):  
Junya Kanda ◽  
Akiyoshi Takami ◽  
Junji Tanaka ◽  
Koichi Miyamura ◽  
Kazuteru Ohashi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Decision Analysis ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
First Remission ◽  
Related Donor

HFE Genotype Is of Donor Origin and Does Not Correlate with Iron Overload Present in Patients after Allogeneic Stem Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3684-3684
Author(s):  
Ann-Kathrin Eisfeld ◽  
Ralph Burkhardt ◽  
Daniel Teupser ◽  
Sabine Schroeder ◽  
Rainer Krahl ◽  
...  
Keyword(s):  
Stem Cell ◽  
Liver Function ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Substantial Proportion ◽  
Unrelated Donor ◽  
Body Iron ◽  
Iron Stores

Abstract Introduction: A substantial proportion of European populations (10–40%) are heterozygous carriers (het) and 0.1–0.3% homozygos (homo) for the hemochromatosis gene (HFE). Patients (pts) with hematologic malignancies often receive multiple blood transfusions (BT). 228 pts undergoing allogeneic stem cell transplantation (SCT) at the University of Leipzig and their donors were screened for HFE. Furthermore, HFE genotype after SCT and body iron stores were correlated with BT and GVHD. Pts and methods: 228 pts (125 m/103 f; median age 46 years) transplanted from Jan, 2001-May, 2004 and their donors [related, n=72 (31.6%); unrelated, n=156 (68.4%)] were screened for HFE. Diagnosis was acute leukemia and MDS in 126 (55%), chronic leukaemia in 51 (23%), lymphoma in 23 (10%), aplastic anemia in 5 (2%), and others in 23 (10%) pts. The majority of pts (n=120; 52.6%) received 12 gray TBI and Cyclophosphamid 120 mg/kg as preparative regimen. ATG 15 mg/kg for 3 days was given to recipients of unrelated SCT. 108 ( 47.4%) pts received Fludarabin 30 mg/m2 for 3 days and 2 gray TBI. 93 pts [36 (38.7%) had a related and 57 (61.3%) an unrelated donor] surviving SCT at least 4 months were further assessed. HFE analysis was performed before and after SCT by PCR techniques using LightCycler, Roche. Serum (s.) iron, transferrin, and ferritin were measured according to IFCC recommendations. Normal iron, transferrin, and ferritin values were 9.5–29.9 μmol/l, 1.9–3.6 g/l, 30–400 ng/ml respectively. Results: Before SCT, HFE mutations were found in 83 (36.4%) pts. 77 pts were het (52 for H63D, 16 for C282Y, 3 for S65C, 6 compound). 6 pts were homo for HFE (5 for H63D and 1 for C282Y). No correlation was found between HFE type and diagnosis. Similarly, mutations were demonstrated in 88 (38.6%) donors. 84 donors were het (50 for H63D, 18 for C282Y, 9 for S65C, 7compound). 4 donors were homo (2 for H63D, 2 for C282Y). After SCT, all 93 (100%) pts for whom data are available expressed donor HFE. Median s. iron, transferrin, and ferritin were 20 μmol/l (range 3.8 – 64.3 ), 1.7 g/l (0.6 – 3), and 952 ng/ml (32.7– 6832.4) respectively. 83 (89.2%) pts showed excess body iron. Median number (no.) of BT was 22 units (range 0–109). In multivariate analysis, median ferritin strongly correlated with the no.of BT (p<0.0001), older age (p=0.0001), and acute leukemia (p=0.0003). Body iron stores did not correlate with HFE genotype prior to or after SCT. Interestingly, acute GVHD of the liver grade I-III present in 8 (8.6%) and isolated SGPT/SGOT elevations seen in 51 (54.8%) pts tended to correlate with iron stores (p=0.06, p=0.1 respectively). Conclusions: 1)Mutations of the HFE were detected in a substantial proportion of donors and pts 2)HFE was always of donor origin after SCT 3)The majority of surviving pts after SCT have markedly increased body iron stores correlating with the no.of BT 4)There seems to be a correlation between iron stores and hepatic GVHD and abnormal liver function after SCT. The influence of iron stores on short- and long-term morbidity and mortality after SCT needs further study. 5)The effect of removal of excess iron by phlebotomy after SCT on GVHD and liver function is currently being assessed.

Donor Selection for Allogeneic Stem Cell Transplantation In Elderly Patients with Advanced MDS: Younger Matched-Unrelated Donor or HLA-Identical Sibling ?

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 912-912
Author(s):  
Nicolaus Kröger ◽  
Tatjana Zabelina ◽  
Anja van Biezen ◽  
Axel R. Zander ◽  
Theo de Witte
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Disease Status ◽  
Unrelated Donor ◽  
Donor Age ◽  
Matched Unrelated Donor ◽  
Unrelated Donors

Abstract Abstract 912 Allogeneic stem cell transplantation from related and unrelated donors is now a reasonable treatment option for elderly patients with advanced MDS. Retrospective studies have shown that donor age is an independent risk factor for outcome of allogeneic stem cell transplantation. By nature there is a strong correlation between patient's age and age of an HLA-identical sibling. Therefore we investigated whether a young matched unrelated donor should be preferred as donor to an elderly HLA-identical sibling in elderly MDS patients who underwent allogeneic stem cell transplantation. We extracted from the MDS-registry of the EBMT 871 patients who received allogeneic stem cell transplantation between 1986 and 2009 and fulfilled the following criterias: 1. patient's age > 50 years, 2. advanced MDS: RAEB, RAEB-t, CMML or sAML, 3. HLA-identical sibling or fully matched unrelated donor transplantation. From those 871 patients with a median age of 57 years (r., 50–73) 706 received stem cells from an HLA-identical sibling and 168 from a matched unrelated donor, either after standard conditioning (n = 387) or after reduced intensity conditioning (n = 481). After a median follow-up of 30 months, the estimated 3 years overall survival did not differ between patients who received stem cells from HLA-identical sibling or from matched unrelated donor (36 % vs. 34 %, p = 0.8). However, the median donor age was significantly higher for HLA-identical sibling than for MUD transplantation: 56 years (r: 35 – 81 y) vs. 34 years (r: 19 – 64) (p < 0.001). While age as continuous variable did not influence survival in HLA-identical sibling transplantation (HR: 1.002, p = 0.8), but did in MUD transplantation (HR: 1.03, p = 0.009), we performed 4 groups according to donor age: HLA-identical sibling transplantation with donor age > 50 years (n = 535) and donor age 30 – 50 years (n = 169) and matched unrelated transplantation with donor age < 30y (n = 60) and donor age > 30y (n = 107). These groups were well balanced according to disease-status, abnormal cytogenetics, and intensity of the conditioning regimen. The estimated 5 years OS for MUD (donorage < 30y) was 41 % and better than for HLA-identical (donor > 50y) with 31 % (p = 0.03) and HLA-identical (donor 30 – 50 y) with 33 % (p = 0.06), but worse than MUD (donor > 30 y) 24 % (p = 0.003). For overall survival, younger donors (< 30y) remained an independent factor for improved survival in a multivariate Cox model: HR: 0.66 (p = 0.03). Other factors influencing survival were disease status (sAML: HR: 1.31, p = 0.03), standard myeloablative conditioning (HR: 1.40, p = 0.002), and abnormal cytogenetic (HR: 1.26, p = 0.07). In comparison to HLA-identical sibling transplantation the hazard ratio for survival remained less than 1 for matched unrelated donors aged 20–35 years (HR: 0.66–0.99), but the hazard ration increased >1 if matched unrelated donor age becomes greater than 35 years. We conclude that for elderly patients (> 50 years) with advanced MDS who need allogeneic stem cell transplantation a younger unrelated donor should be preferred to an HLA-identical sibling donor. Disclosures: No relevant conflicts of interest to declare.

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