Unrelated donor search and selection practices by hematopoietic cell transplant (HCT) physicians and search coordinators are not standardized across centers, and what defines urgent TtT is not well ...understood.
To evaluate donor search practices, HCT urgency definition based on disease risk, and strategies utilized in the event of a low likelihood of identifying an HLA 8/8 matched unrelated donor (MUD).
From February-May 2018, NMDP's Histocompatibility Advisory Group conducted a web-based survey of ASBMT-member physicians and search coordinators in the United States (US).
A total of 317/904 physicians (37%) and 225/333 coordinators (68%) responded. Most centers (95%) were represented; 72% had at least one physician and 85% at least one coordinator respondent. There were no statistically significant differences between physician and coordinator responses. Most (77%) indicated that donor selection decisions were made by individual physicians. Uniform use of a selection algorithm (11%) or a single decision maker (7%) for the program was uncommon. Urgent TtT was most commonly (89%) defined by respondents as HCT occurring within 4-6 weeks of search initiation (Figure 1), although 65% indicated that physicians also have individual systems to determine urgency. Higher physician-perceived HCT urgency was associated with higher disease risk index; for example, for acute myeloid leukemia (AML), 27%, 60% and 86% of physicians indicated TtT of <6 weeks for patients with intermediate risk, complete remission disease; adverse risk, complete remission; and primary induction failure/relapse, respectively (Figure 2). For urgent cases with a low probability of identifying an 8/8 MUD, 77% of respondents endorsed a short (1-2 weeks) unrelated donor search before proceeding to an alternative donor source. Strategies pursued in the setting of a low probability of identifying a MUD for urgent cases are shown in Figure 3, and included 7/8 MUD, cord blood, haploidentical donor, non-HCT therapy, and research protocol driven source selection (all applicable options could be selected). The majority (>90% agree/strongly agree) of respondents reported good communication among physicians and search coordinators regarding desired TtT, preferred donor type, and alternatives when the preferred source was unavailable.
This national survey clarified current donor selection decision making practices in the US and defined urgent TtT. These data provide insight to NMDP on potential solutions to support the path to transplant, such as highlighting futile searches and providing alternative donor options at the time of search initiation.
Abstract Adolescents and young adults (AYAs, ages 15 to 40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in ...survival after myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (n = 981), AYAs (n = 1218), and older adults (n = 469) who underwent transplantation over 3 time periods: 1990 to 1995, 1996 to 2001, and 2002 to 2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment-related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15 and 25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplantation practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.
Abstract The impact of non-HLA patient factors on the match of the selected unrelated donor (URD) for hematopoietic cell transplantation (HCT) has not been fully evaluated. National Marrow Donor ...Program (NMDP) data for 7486 transplants using peripheral blood stem cells (PBSCs) or bone marrow from years 2000 to 2005 were evaluated using multivariate logistic regression to identify independent non-HLA patient factors associated with completing a more closely matched URD transplant. Advanced (intermediate- and late-stage) disease was significantly associated with an increased likelihood of transplant using a less-matched (partially matched or mismatched) donor. Additionally, Black patients were 2.83 times, Asian patients 2.05 times, and Hispanic patients 1.73 times more likely to have a less-matched HCT donor than Caucasian patients. Younger patients, HCT at lower volume centers, and in earlier years had significantly higher likelihood of having a less HLA matched URD transplant. Our analysis provides encouraging evidence of HLA matching improvement in recent years. Initiating a patient's URD search early in the disease process, especially for patients from non-Caucasian racial and ethnic groups, will provide the best likelihood for identifying the best available donor and making informed transplant decisions.
Abstract Non-Hodgkin lymphoma (NHL) disproportionately affects older patients, who do not often undergo allogeneic hematopoietic cell transplantation (HCT). We analyzed Center for International Blood ...and Marrow Transplant Research data on 1248 patients age ≥40 years receiving reduced-intensity conditioning (RIC) or nonmyeloablative (NMA) conditioning HCT for aggressive (n = 668) or indolent (n = 580) NHL. Aggressive lymphoma was more frequent in the oldest cohort 49% for age 40 to 54 versus 57% for age 55 to 64 versus 67% for age ≥65; P = .0008). Fewer patients aged ≥65 had previous autografting (26% versus 24% versus 9%; P = .002). Rates of relapse, acute and chronic GVHD, and nonrelapse mortality (NRM) at 1 year post-HCT were similar in the 3 age cohorts (22% 95% confidence interval (CI), 19% to 26% for age 40 to 54, 27% 95% CI, 23% to 31% for age 55 to 64, and 34% 95% CI, 24% to 44% for age ≥65. Progression-free survival (PFS) and overall survival (OS) at 3 years was slightly lower in the older cohorts (OS: 54% 95% CI, 50% to 58% for age 40 to 54; 40% 95% CI, 36% to 44% for age 55 to 64, and 39% 95% CI, 28% to 50% for age ≥65; P < .0001). Multivariate analysis revealed no significant effect of age on the incidence of acute or chronic GVHD or relapse. Age ≥55 years, Karnofsky Performance Status <80, and HLA mismatch adversely affected NRM, PFS, and OS. Disease status at HCT, but not histological subtype, was associated with worse NRM, relapse, PFS, and OS. Even for patients age ≥55 years, OS still approached 40% at 3 years, suggesting that HCT affects long-term remission and remains underused in qualified older patients with NHL.
Adolescents and young adults (AYAs, ages 15–40 years) with cancer have not experienced survival improvements to the same extent as younger and older patients. We compared changes in survival ...following myeloablative allogeneic hematopoietic cell transplantation (HCT) for acute lymphoblastic leukemia (ALL) among children (N=981), AYAs (N=1218) and older adults (N=469) who were transplanted over three time periods: 1990–1995, 1996–2001 and 2002–2007. Five-year survival varied inversely with age group. Survival improved over time in AYAs and paralleled that seen in children; however, overall survival did not change over time for older adults. Survival improvements were primarily related to lower rates of early treatment related mortality in the most recent era. For all cohorts, relapse rates did not change over time. A subset of 222 AYAs between the ages of 15–25 at 46 pediatric or 49 adult centers were also analyzed to describe differences by center type. In this subgroup, there were differences in transplant practices among pediatric and adult centers, although HCT outcomes did not differ by center type. Survival for AYAs undergoing myeloablative allogeneic HCT for ALL improved at a similar rate as survival for children.
Non-Hodgkin lymphomas (NHL) disproportionately affect older patients who uncommonly receive allogeneic hematopoietic cell transplantation (HCT). We analyzed CIBMTR data on 1248 patients ≥40 years ...receiving reduced-intensity conditioning (RIC) or non-myeloablative (NMA) HCT for aggressive (n=668) and indolent (n=580) NHL. Aggressive lymphoma was more frequent in the oldest cohort (age 40–54) 49% vs. (55–64) 57% vs. (≥65) 67% p=0.0008; fewer patients ≥65 had prior autografting 26% vs. 24% vs. 9%; p=0.002). Rates of relapse, acute and chronic GVHD and non-relapse mortality (NRM) at one year were similar 22%, 95% confidence interval (CI) 19–26%; 27%, 95% CI 23–31%; 34%, 95% CI 24–44%. Progression-free (PFS) and overall (OS) survival at 3 years was slightly lower in older cohorts OS:54%, 95% CI 50–58%; 40%, 95% CI 36–44%; 39%, 95% CI 28–50%; p<0.0001. Multivariate analysis revealed no significant effect of age on acute or chronic GVHD or relapse. Age ≥55 years, Karnofsky performance status <80, and HLA-mismatch adversely impacted NRM, PFS, and OS. Disease status at HCT, but not histologic subtype, worsened NRM, relapse, PFS and OS. Even for patients ≥55 years, OS still approached 40% at 3 years suggesting HCT effects long-term remissions and remains underutilized in qualified older patients with NHL.
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