Is a matched unrelated donor search needed for all allogeneic transplant candidates?
| Autor: | Julianne Chen, Gabriela Rondon, Partow Kebriaei, Stefan O. Ciurea, Betul Oran, Kai Cao, Mohammed El Shazly, Michele Alvarez, Chitra Hosing, Denái R. Milton, Majdi Aljadayeh, Richard E. Champlin, Issa F. Khouri, Jorge M. Ramos Perez, Uday R. Popat, Marina Konopleva, Jin Im, Piyanuch Kongtim, Maria C.B. Bittencourt, Qaiser Bashir, Gheath Alatrash, Rohtesh S. Mehta |
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| Rok vydání: | 2018 |
| Předmět: |
Homologous
Adult Disease status medicine.medical_specialty Multivariate analysis Allogeneic transplantation Adolescent Clinical Trials and Observations Immunology Newly diagnosed Haploidentical Biochemistry Young Adult 03 medical and health sciences 0302 clinical medicine Risk Factors Clinical Research Internal medicine parasitic diseases Transplantation Homologous Humans Medicine Child Aged Transplantation business.industry Histocompatibility Testing Remission Induction Hazard ratio Hematopoietic Stem Cell Transplantation Organ Transplantation Cell Biology Hematology Odds ratio Matched Unrelated Donor Middle Aged Survival Analysis surgical procedures operative Haplotypes Hematologic Neoplasms 030220 oncology & carcinogenesis Transplantation Haploidentical Unrelated Donors business 030215 immunology |
| Zdroj: | Blood advances, vol 2, iss 17 |
| ISSN: | 2473-9537 2473-9529 |
| Popis: | Introduction An HLA-matched unrelated donor (MUD) has been accepted as the next best option for patients who do not have a matched-related donor (MRD) available. However, identification of a MUD may be challenging due to donor availability for some populations. In addition, the MUD search and procurement of stem cell product usually takes much longer than that of a related donor, many patients may develop progressive disease or become medically unfit while waiting for a MUD transplant, which might have a negative impact on overall survival. Therefore, in this study we hypothesized that certain groups of patients may not benefit from performing a MUD search and sought to evaluate availability of a MUD donor, ability to proceed to transplant with a MUD, as well as transplant outcomes for all patients who had a MUD search started at our institution. Methods All consecutive patients with a diagnosis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who had a MUD search performed between 2013 and 2015 were included. All patients had high resolution HLA typing at HLA-A, -B, -C, -DRB1 and -DQB1 performed by DNA sequencing and had unrelated donor search by the NMDP. According to standard operating procedures, a MUD search was initiated when no MRD was available, or as soon as HLA typing was completed. If no 10/10 MUD was available, the choice between a 9/10 MUD, haploidentical or umbilical cord blood (UCB) was based on the treating physician's decision. Results The analysis included 242 patients with a median age of 58 years (range 9-80 years), 123 patients (51%) were male, 182 patients (75%) were Caucasian and 190 (79%) had common haplotypes. One hundred thirteen patients (47%), 35 (14%), 43 (18%) and 49 (20%) were in complete remission, primary induction failure (PIF), relapse/refractory and newly diagnosed, respectively. One hundred sixty (66%) patients had a 10/10 MUD identified. The majority of Caucasians (85%) had common haplotypes compared with only 58% of patients with other races (P Only 85 of 160 (53%) patients proceeded to MUD transplantation, while 66 (27%) patients received transplants from other donor types [9 (4%) 9/10 MUD, 20 (8%) haploidentical, 22 (9%) UCB and 15 (6%) MRD transplant], and 91 (38%) patients did not receive a transplant. The median time from MUD search to 10/10 MUD, MRD, haploidentical, 9/10 MUD and UCB transplant was 2.9, 2.3, 3.5, 4.6 3.2 months, respectively (P=0.002). Taken together, Caucasian race and having common haplotype were independently associated with 10/10 MUD identification with odds ratio (OR) of 6.8 (95%CI 3.1-14.9) and 39 (95%CI 13.9-110.4), respectively and with proceeding to MUD transplantation (OR 7.7, 95%CI 2.7-21.7 and OR 66, 95%CI 3.9->999), respectively. A multivariable analysis (MVA) for PFS of patients who received a transplant showed significant impact on transplant outcomes for disease status, cytogenetics and time from a MUD search to transplant, while donor type did not impact transplant PFS (Table 1). A second MVA for PFS was performed for all patients who had a MUD search. Patients who had intermediate/favorable cytogenetics, de novo AML, newly diagnosed/complete remission and received a transplant experienced significantly better PFS compared with their counterparts (Table 1, Figure 1). The highest percentages of 10/10 MUD identification, MUD transplant and PFS were observed for Caucasians who were newly diagnosed/complete remission with common haplotype (60% MUD identified, 69% MUD transplant, 3-year PFS rate of 46%), whereas the patient group with the lowest percentages was non-Caucasians with primary induction failure/relapsed/refractory and had uncommon haplotype (1% MUD identified, 0% MUD transplant, 3-year PFS rate of 0%). Conclusions Race, haplotype frequency and disease status at the time of MUD search influence probability to identify a MUD and receive a transplant. Patients with low likelihood to receive a MUD transplant may proceed to a haploidentical transplant as soon as indicated, as this approach does not appear to compromise transplant outcomes. Disclosures Konopleva: Stemline Therapeutics: Research Funding. Oran:AROG pharmaceuticals: Research Funding; Celgene: Consultancy, Research Funding; ASTEX: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding. |
| Databáze: | OpenAIRE |
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