Older Patients with AML Undergoing Matched Related Allogeneic Transplantation Have Significantly Older Donors but Equivalent Survival as Patients Receiving Unrelated Donor Transplants

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2356-2356
Author(s):  
Brian T. Hill ◽  
Lisa Rybicki ◽  
Brian J. Bolwell ◽  
Robert Dean ◽  
Brad Pohlman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Older Patients ◽  
Conflicts Of Interest ◽  
Performance Status ◽  
Cleveland Clinic ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Donor Age ◽  
Hematopoietic Cell Transplant ◽  
Unrelated Donors

Abstract Abstract 2356 Introduction: Allogeneic stem cell transplantation (SCT) is commonly offered to patients with acute myeloid leukemia (AML) over the age of 55 with good performance status. For this patient population, potential sibling donors are necessarily older and have more comorbidities than siblings of younger patients. It is not known whether the advanced donor age of older patients outweighs the beneficial effect of having a sibling donor. To address this question, we retrospectively analyzed data from 62 consecutive patients who received allogeneic SCT at the Cleveland Clinic from 1990–2009. Methods: Inclusion criteria were: age ≥ 55 years, diagnosis of AML, and history of myeloablative or nonmyeloablative allogeneic SCT from related or unrelated adult donors. 31 patients underwent transplantation from matched related donors (30 siblings, 1 cousin). 31 patients received unrelated donor transplants. The median age was 59 for patients with related and unrelated donors (P=0.89). There was an equal percentage of males (64.5%) in both groups (P=1.0). There was an equivalent distribution hematopoietic cell transplant comorbidity index scores of low, intermediate and high for patients with related and unrelated donors (38.7%, 37.1% and 24.2% vs. 38.7%, 32.3%, and 29.0% P = 0.65). 45.2% of patients with related donors underwent myeloablative conditioning vs. 54.8% for patients with unrelated donors (P =0.61). Results: Sibling donors were significantly older than unrelated donors [median 59 years (range 41–75) vs. 36 (range 24–58), P < 0.001]. The incidence of acute and chronic graft-versus-host disease (GVHD) was similar in both groups. At five years, the cumulative incidence of relapse (43.2% vs. 38.7%, P = 0.88), non-relapse mortality (48.1% vs. 48.8%, P =0.91) and overall survival (17.2% vs. 24.1%, P =0.88) were similar for recipients of matched related and unrelated donor transplants. Older donor age was not predictive of death in univariate or multivariate analysis. Kaplan-Meier estimates of overall survival for recipients of related and unrelated donor transplants are shown. Conclusion: Patients with AML 55 years or older who underwent related donor transplantation had significantly older donors but equivalent survival when compared to patient who underwent unrelated donor transplantation. Advanced donor age should not be a contraindication to allogeneic SCT for older patients with AML. Disclosures: No relevant conflicts of interest to declare.

Graft-Versus-Leukemia Effect Is Equivalent in Recipients of Matched Sibling and Matched Unrelated Donor Conventional Hematopoietic Cell Transplant.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3049-3049
Author(s):  
Mukta Arora ◽  
Steven Pavletic ◽  
Claudio Anasetti ◽  
John Barrett ◽  
Tao Wang ◽  
...  
Keyword(s):  
Chronic Phase ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Free Survival ◽  
Graft Versus Leukemia ◽  
Unrelated Donors ◽  
Matched Sibling ◽  
Relapse Rates ◽  
Related Mortality

Abstract Anti-leukemia effects of allotransplants are largely mediated by immune mechanisms collectively termed graft-versus-leukemia (GvL). We postulated that allotransplants from HLA-matched unrelated donors (URD) have greater GvL activity than similar transplants from HLA-identical siblings because of greater genetic-disparity between donor and recipient. We tested this hypothesis in 4099 adult recipients of HLA-matched sibling (N= 3158) or 8/8 HLA-allele-matched URD (N= 941) transplants for acute leukemia (AML and ALL) and chronic myeloid leukemia (CML) receiving conventional transplants between 1995–2004 and reported to CIBMTR. Relapse, transplant-related mortality (TRM) and leukemia-free survival (LFS) were compared between the cohorts. Contrary to our hypothesis, relapse rates at 5 y were similar in patients receiving sibling and URD transplants. More TRM was seen in URD cohort in early AML [sibs 24% (20–27%) versus URD 40% (31–50%), p=0.001], advanced ALL or AML [sibs 31% (25–36%) versus URD 44% (35–53%), p= 0.01] and early CML [sibs 31% (28–33%) versus 38% (32–44%), p=0.02]. LFS was superior with sibling donors in early- and advanced- AML and CML. These data indicate comparable GvL-activity of HLA matched URD and HLA-identical sibling transplants in AML, ALL and CML receiving conventional transplants despite greater genetic disparity. Early Disease (1stremission or 1st chronic phase) Outcome at 5 years Sibling donor URD P AML (N= 878) 760 118 Relapse 15 (13–18)% 22 (15–30)% 0.1 LFS 61 (57–65)% 38 (28–48)% <0.001 ALL (N= 333) 271 62 Relapse 23 (18–29)% 15 (7–25)% 0.13 LFS 46 (39–53)% 42 (29–55)% 0.6 CML (N=1443) 1152 291 Relapse 6 (5–8)% 5 (3–8)% 0.5 LFS 63 (60–66)% 57 (51–63)% 0.06 Intermediate Disease (2nd or subsequent remission or accelerated phase) AML (N= 268) 180 88 Relapse 22 (16–29)% 21 (13–30)% 0.8 LFS 48 (40–56)% 41 (30–52)% 0.3 ALL (N= 172) 111 61 Relapse 32 (24–42)% 36 (24–48)% 0.7 LFS 27 (18–36)% 24 (14–37)% 0.8 CML (N=263) 173 90 Relapse 22 (15–28)% 16 (9–24)% 0.5 LFS 36 (29–44)% 35 (26–46)% 0.9 Advanced Disease (Not in remission or blast phase) AML (N= 423) 294 129 Relapse 46 (40–52)% 43 (34–51)% 0.6 LFS 23 (18–29)% 13 (8–20)% 0.01 ALL (N= 152) 88 64 Relapse 52 (42–63)% 48 (35–60)% 0.6 LFS 10 (4–18)% 5 (1–12)% 0.2 CML (N=76) 49 27 Relapse 35 (23–49)% 39 (20–60)% 0.8 LFS 21 (11–35)% 0 <0.001

Effective Management of Patients with Leukemic Transformation of Myelofibrosis.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4967-4967
Author(s):  
Shyamala C. Navada ◽  
John Mascarenhas ◽  
Vesna Najfeld ◽  
Ronald Hoffman
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Leukemic Transformation ◽  
Transfusion Requirements

Abstract 4967 Introduction Myelofibrosis (MF) is a clonal stem cell Philadelphia chromosome negative myeloproliferative neoplasm (MPN) characterized by progressive cytopenias, massive splenomegaly, early satiety, and a hypercatabolic state manifested by fevers, fatigue, and weight loss. Approximately 10-20% of MF patients will transform to acute myeloid leukemia (AML) over a 10-year period with a median overall survival at time of transformation of 2.6 months (Mesa 2005). In a multivariate analysis, peripheral blood blast count > 3% and/or a platelet count < 100 × 109/L at time of diagnosis of MF were independent risk factors for leukemic transformation (LT) (Huang 2008). Standard induction chemotherapy improved survival to 3.9-5 months (Mesa 2005, Tam 2008). Survival was decreased due to a high relapse rate and treatment-related mortality. Patients who received an allogeneic stem cell transplant early in the disease course had superior survival. We describe the outcome of ten consecutive patients with MF-LT at our institution. Patients and Methods A retrospective chart review was performed to evaluate patients with MF-LT, including clinical characteristics, therapies administered, and survival outcomes. Between the years of 2007 and 2009, ten MF-LT patients were identified in our institution. The median age was 66 (range 45-77) with 60 percent male and 40 percent female patients. Thirty percent (3/10) of patients were JAK2 V617F positive. Seven patients were cytogenetically abnormal and three had a normal karyotype. Chromosomal abnormalities included +1q (2 pts), +8 (2 pts), -7 (2 pts), inv 3 (1 pt), and t(6;9) (1 pt). Fifty percent of patients had a post-essential thrombocythemia related MF, while 30 percent had an MDS/MF overlap syndrome. Time to LT ranged from 3 months to 12 years with a median of 12 months. In three cases, there was discordance between bone marrow blasts by immunohistochemical staining and peripheral blood manual count. Six patients were treated with decitabine at 20 mg/m2 for 5 days (for two to ten cycles), and four received reduced intensity conditioning allogeneic stem cell transplantation (RIC-ASCT). Patients were eligible for RIC-ASCT if they were under 70 years of age, had no significant comorbidities, and had either an HLA compatible sibling or an unrelated donor with at most one mismatched allele. Results The median survival from diagnosis of LT with the use of decitabine has not yet been reached but exceeds 7.5 months in this patient population. Two out of six patients treated with decitabine died 6 and 8 months after LT. The remaining four patients are still alive at 6, 7, 9, and 36 months after LT and are actively receiving therapy. Four out of six patients who received decitabine had subjective improvement in fatigue as well as decrease in splenomegaly. Three out of six patients had a decrease in transfusion requirements. The four patients who underwent RIC-ASCT are all alive after a median follow-up of 16.5 months with no evidence of leukemia in the bone marrow. Conclusions These results demonstrate that single-agent decitabine for those who are not eligible for transplant or RIC-ASCT for eligible patients, leads to a significant improvement in overall survival. Further investigation using these therapeutic modalities is warranted given the aggressive nature of this disease. Furthermore, the noted discordance between bone marrow and peripheral blood blast percentage most likely reflects leukemic cell production originating at sites of extramedullary hematopoiesis. Disclosures No relevant conflicts of interest to declare.

The Presence Of 1 / 8 HLA Mismatch Do Not Hamper Survival After Allogeneic Stem Cell Transplantation Using Immunoprophylaxis With Sirolimus-Tacrolimus

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4529-4529
Author(s):  
Rocío Parody ◽  
Lucía López-Corral ◽  
Oriana Lopez Godino ◽  
Irene García Cadenas ◽  
Vazquez Lourdes ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Stem Cell Source ◽  
Unrelated Donors

Several studies from the IBMTR have shown that overall survival (OS) is reduced by 10% for each mismatched at obligatory locus (A,B,C or DRB1) after allogeneic hematopoietic stem cell transplant (Allo-HSCT) (Lee et al. Blood 07). In the setting of 7/8 mismatched allo HSCT, different T-cell depletion strategies are frequently used in an attempt to decrease GVHD assuming a higher risk of infections and relapse. Data from the IBMTR are mostly based on series of patients who received Cyclosporine /Tacrolimus (TKR) plus methotrexate as immunoprophylaxis. As far as we know, the effect of sirolimus (SRL)/TKR combination on overall outcomes of transplant, regardless HLA mismatched, has not yet been evaluated. With this background, we retrospectively analysed a series of 151 adult patients who received SRL/TKR based reduced intensity (RIC)-alloHSCT in 6 Spanish centres, from January 2007 to September 2012 (median follow up in alive patients 19 months, range 4-47), comparing overall outcomes according HLA compatibility in obligatory locus A,B,C, DRB1: 8/8 (n:129) vs 7/8 (n:22). No in vivo or ex vivo T depletion was used. Patients characteristics are not significantly different between both groups. Median age was 53 years (17-70) and the two most common diseases (56% of cases) were AML and NHL. The most frequent stem cell source was peripheral blood (94%) and 76% transplants were from volunteer unrelated donors. Forty nine per cet of patients had active disease at the time of transplant. Comparing 8/8 vs 7/8 alloHSCT, non statistically significant differences were found in 3 years-OS (56,4% vs 69%, p=0.7), 1 year-non-relapse mortality [12 % (7-20) vs 14% (5-42), p=0.8], and 3 year-relapse rate: 28% (19-43) vs 20% (9-50), p=0.8, respectively. Cumulative incidence of acute GVHD was significantly higher in 7/8 alloHSCT [68% (49-94) vs 41% (32-51), p=0.004] but no differences were observed with respect to neither III-IV acute GVHD (5 vs 9%, p:0.6) nor global (35 vs 51%, p=0.6) and extensive (20 vs 30%, p=0.9) chronic GHVD in 8/8 vs 7/8, respectively. The present study shows favorable outcomes of SRL/TKR combination in the setting of RIC alloHSCT, with an overall survival in the range of 55-70%%, and non significant differences in overall outcomes regardless the presence of any mismatched at obligatory locus. Comparative studies with a larger sesries is desirable to confirm these results. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Pre-Transplant C-Reactive Protein (CRP), Ferritin and Albumin As Biomarkers to Predict Transplant Related Mortality (TRM) after Allogeneic Hematopoietic Cell Transplant (HCT)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 422-422 ◽  
Author(s):  
Andrew S. Artz ◽  
Brent R. Logan ◽  
Xiaochun Zhu ◽  
Görgün Akpek ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Overall Survival ◽  
Risk Score ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Combined Model ◽  
Biomarker Panel ◽  
Co Morbidity ◽  
Related Mortality

Abstract HCT entails substantial TRM justifying continued efforts to better risk stratify patients. Single institutional studies have suggested several clinically available biomarkers of CRP, ferritin and albumin influence TRM if not overall survival (OS). We sought to confirm the independent prognostic value of these biomarkers in a large multi-institutional cohort. The study population consisted of 784 adults with AML in remission (80%) or MDS (20%) undergoing unrelated donor HCT between 2008 and 2010 and available cryopreserved samples through the Center for International Blood and Marrow Transplant Research (CIBMTR) repository. CRP and ferritin were centrally quantified by ELISA from cryopreserved plasma whereas albumin levels obtained from center reported data. Correlation studies for biomarkers required log transformation of CRP and ferritin to produce a normal distribution. Multivariate models were fitted separately for each biomarker applying protocol specified thresholds generated from the literature of CRP > 10 mg/L, ferritin > 2500 ng/mL, albumin < 3.5 g/dL on TRM. Further analysis explored optimal cutpoints for this cohort for all significant clinical variables for TRM. HCT characteristics included a median age of 50 (range 18-78) years, HCT-CI (co-morbidity index) 3 or more in 35%, single allele/antigen mismatch (7/8) in 23%, PB as stem cell source in 83%, and myeloablative conditioning in 72%. Biomarker data were available in 783, 781 and 695 cases for CRP, ferritin and albumin respectively. The median values and ranges for each biomarker were as follows: 5.0 mg/L (0.3 - 316) for CRP, 1148 ng/mL (51 – 14,298) for ferritin and 3.6 g/dL (0.6-5.3) for albumin. Log transformed CRP and ferritin showed a modest correlation (r=0.35, P<0.001), and log CRP was marginally associated with albumin (r=-0.12, P=0.002). HCT-CI had no correlation to CRP and albumin. Higher ferritin was associated with HCT-CI (P=0.014) and disease (P<.001). In the entire population, TRM and overall survival (OS) at 2 years were 23% and 54%, respectively. The table shows the independent association of each biomarker with TRM and OS. Ferritin had no association with these outcomes but only 12% had levels above 2500 by ELISA. The optimal cutpoints for TRM were defined as follows: CRP > 3.67 (HR=1.75, P=0.001); albumin < 3.4 (HR 1.70, P <0.001); and ferritin as a continuous variable (HR 1.30, P = 0.008). A risk score was created modeling optimal biomarker thresholds to predict TRM based on the following formula: risk score = 0.44633*I(CRP>3.67)+0.18330*ln(Ferritin)+0.44730*I(albumin<3.4), where “I” is an indicator function and represent 1 or 0 depending on the presence of the abnormal biomarker level in parenthesis. The risk score included adjustment for HCT-CI. The biomarkers did not influence the incidence of relapse or graft-versus-host disease with any of these models. Elevated CRP and ferritin and decreased albumin prior to HCT were associated with impaired transplant survival, primarily through higher TRM. Integration of a biomarker panel in clinical practice once validated can enhance risk-stratification, improve adjustment for comparative studies and point towards the design of biomarker driven trials. Abstract 422. Table: Multivariate analysis of TRM and OS for biomarkers, and biomarker panel risk score* Abnormal, N (%) Transplant related mortality Overall Survival Biomarker HR 95% CI P HR 95% CI P Protocol defined CRP >10 mg/L 184 (24) 1.52 1.11 – 2.07 0.008 1.22 0.98 – 1.53 0.072 Ferritin >2500 ng/mL 93 (12) 1.26 0.84 – 1.88 0.27 1.15 0.86 – 1.54 0.35 Albumin < 3.5 g/dL 290 (42) 1.48 1.10 – 2.0 0.010 1.39 1.13 – 1.72 0.002 Optimal threshold, combined model ** CRP >3.67 mg/L 497 (64) 1.56 1.11 – 2.19 0.010 1.24 1.00 – 1.55 0.054 Log(Ferritin), linear n/a 1.20 0.99 – 1.46 0.07 1.20 1.04 – 1.38 0.010 <3.4 g/dL 203 (29.5) 1.58 1.16 – 2.15 0.004 1.37 1.10 – 1.72 0.005 Biomarker Score ** N Low (<1.5) 200 1.0 - - 1.0 Intermediate (1.5-2.0) 331 1.66 1.10-2.49 0.015 1.38 1.06-1.80 0.017 High (>2.0) 159 2.72 1.77-4.19 <0.001 2.01 1.51-2.70 <0.001 * biomarkers adjusted for significant covariates of BMI, disease, mismatch, and CMV serostatus and stratified on conditioning regimen ** combined model includes all biomarkers and HCT-CI Disclosures No relevant conflicts of interest to declare.

Permissive HLA-DPB1 Mismatching Compared to a Non-Permissive Mismatching Significantly Improves Overall Survival Following Allogeneic Transplantation In Patients with Both 10/10 and 9/10 Matched Unrelated Donors

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 227-227 ◽  
Author(s):  
Bronwen E. Shaw ◽  
Katharina Fleischhauer ◽  
Mari Malkki ◽  
Theodore Gooley ◽  
Elisabetta Zino ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Haematopoietic Stem Cell ◽  
Unrelated Donor ◽  
Matched Pairs ◽  
Significant Difference ◽  
Unrelated Donors ◽  
Matching Criteria

Abstract Abstract 227 It is well established that the use of a donor matched for 9–10/10 alleles at HLA-A,-B,-C,-DRB1,-DQB1 significantly improves overall survival (OS) after unrelated donor (UD) haematopoietic stem cell transplantation (HSCT). Whilst the matching status for HLA-DPB1 alleles has been shown to influence transplant complications (relapse and graft-versus-host disease (GVHD), its impact on survival has not been well defined. The current unmet need in clinical practice is an approach to stratify selection criteria when a clinician is confronted with the choice between several 10/10 or 9/10 matched unrelated donors. There is now considerable interest in exploring different types of matching criteria to define permissive HLA-DPB1 mismatches which may be associated with an improved outcome. We have previously shown that HLA-DPB1 permissiveness can be functionally defined by the characterization of shared T cell epitopes (TCE) recognized by alloreactive T cells. In this model, allelic HLA mismatches are classified as permissive if they do not involve TCE disparities, and as non-permissive if they do. Using this concept, we developed two overlapping algorithms of permissivity for allelic HLA-DPB1 mismatches, on the basis of 3 (TCE3) or 4 (TCE4) groups of DPB1 alleles encoding immunogenic TCE. Data from relatively small prospective studies has shown a worse outcome to be associated with non-permissive DPB1 TCE disparities. Here, we present outcomes in 9123 UD-HSCT pairs, collected through the International Histocompatibility Working Group (IHWG). The cohort was comprised of 5809 10/10 matched transplant pairs and 3314 9/10 matched pairs. Within the 10/10 and 9/10 matched pairs three groups of patients were identified: 1. Zero DPB1 mismatches (i.e. allele matched), 2. Permissive DPB1 mismatch, 3. Non-permissive DPB1 mismatch. The model was adjusted for disease severity, source of stem cells, conditioning regimen, use of T-cell depletion, patient/donor gender and patient age. In line with DPB1 allele frequencies in worldwide populations, the number of transplants scored as permissive was higher for TCE3 (4398/7270 [60.4%]) than for TCE4 (2577/7270 [35.4%]). Using the DPB1 permissive mismatch transplants as the reference group (either 10/10 or 9/10 matched), we showed that DPB1 allelic matches resulted in similar survivals to DPB1 permissive mismatches, both in the 10/10 (HR 0.96, p=0.498 for TCE3 and HR 0.99, p=0.85 for TCE4) and the 9/10 setting (HR 0.97, p=0.70 for TCE3 and HR 0.99, p=0.96 for TCE4). In contrast, survival was significantly worse in the presence of a non-permissive TCE3 or TCE4 mismatch, both in the 10/10 (HR 1.15, p=0.0005 for TCE3 and HR 1.13, p=0.0035 for TCE4) and in the 9/10 matched setting (HR 1.13, p=0.0140 for TCE3 and HR 1.11, p=0.0448 for TCE4). The survival detriment appeared to be due to a significantly increased non-relapse mortality (TCE3: 10/10 HR 1.27, p<0.001 and 9/10 HR 1.21, p=0.0001; TCE4: 10/10 HR 1.24, p<0.001 and 9/10 HR 1.13, p=0.0514), as well as an increase in grades II-IV acute GVHD (TCE3: 10/10 HR 1.17, p<0.001 and 9/10 HR 1.29, p<0.001; TCE4: 10/10 HR 1.12, p=0.0035 and 9/10 HR 1.19, p<0.0001). There was no significant difference in disease relapse between permissive and non-permissive mismatched pairs. Finally, using the 10/10 DPB1 permissive mismatched group as a reference, we found survival to be similar for 10/10 DPB1 non-permissive (HR 1.15) and 9/10 DPB1 permissive (HR 1.20) or DPB1 allele matched (HR 1.17) transplants. In conclusion, our results suggest that extending donor selection to include HLA-DPB1 both allelic and functional TCE matching may result in better prediction of survival for patients. These findings provide an attractive new algorithm to stratify donor choice when several well-matched UD are identified. Disclosures: No relevant conflicts of interest to declare.

Donor Choice for Allogeneic Stem Cell Transplantation for AML – A Retrospective Single Centre Long-Term Analysis,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4147-4147
Author(s):  
Francis Ayuk ◽  
Friedericke Bernhardt ◽  
Tatjana Zabelina ◽  
Thomas Stübig ◽  
Haefaa Alchalby ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cox Regression ◽  
Unrelated Donor ◽  
Donor Age ◽  
Sibling Donor ◽  
Remission Status ◽  
Unrelated Donors

Abstract Abstract 4147 Introduction: AML is one of the most common indications for allogeneic hematopoietic stem cell transplantation (allo-HSCT). A matched sibling donor (matched related donor, MRD) is generally considered preferable to an unrelated donor (UD). It has been reported before that donor age may influence outcome of allo-HSCT. Sibling donors of older patients will generally be old as well. How a young unrelated donor compares with an old sibling donor is unclear. In this retrospective study we evaluate the influence of donor age on outcome of MRD and UD allo-HSCT and compare the impact of young unrelated donors vs. old related donors on overall survival (OS). Patients and Methods: We performed a retrospective analysis of 298 consecutive patients transplanted for AML at our center between January 2000 and December 2009. Median follow-up was 56 months. The median age of donors and patients were 39 and 50 yrs. respectively. These two ages were used as cut-off points for young and old donors and patients respectively. Accordingly, four donor aged groups were assigned: UD ' 39 years, UD > 39 yrs, MRD ≤ 39 yrs and MRD > 39 yrs. Analyses were performed in the more homogeneous population of patients in CR at time of transplant (n = 170) as well for patients older than 50 years and in CR at time of transplant (n = 77). Patient characteristics for the 170 Patients in CR are summarized in table 1. Results: In the cox-regression multivariate analysis of all 298 patients including factors significant in the univariate analysis (conditioning intensity, cytogenetic risk group, remission status at time of transplant and donor age) remission status (RR: 1.88, p < 0.001) and cytogenetic risk (RR: 5.50, p = 0.004) significantly impacted overall survival (OS). Donor age (p = 0.08) and patient age (p = 0.063) tended to influence OS in this group. In the more homogenous group of 170 patients who were in CR at time of transplantation the Kaplan Meier estimated 5 yr OS was 66% (95% CI: 54%-78%) for patients transplanted from UD ≤ 39 yrs, 41% (95% CI: 25–57%) for UD >39 yrs, 61% (41–81%) for MRD ≤ 39 yrs and 33% (19–47%) for MRD > 39 yrs (p =0.002 comparing all 4 groups), fig. 1. OS of patients with UD ≤ 39yrs was significantly better than for those with MRD > 39 yrs (66% vs. 33%, p = 0.001). In the multivariate cox-regression analysis (including donor age, patient age and cytogenetic risk) only donor age (p = 0.001) and cytogenetic risk (p = 0.011) significantly impacted OS whereby MRD > 39 yrs. was associated with poorer OS compared to UD ≤ 39 yrs (RR: 3.07, p< 0.001). Further subgroup analyses of patients > 50 years old and in CR at time of transplant (n = 77) revealed similar findings with 5 yr OS of 62% for UD ≤ 39 yrs and 25% for MRD >39 yrs (p = 0.016). Conclusions: In patients undergoing allo-HSCT for AML our findings suggest that young unrelated donors may improve survival outcome as compared to old related donors. Further studies are necessary to confirm these findings and better define possible age limits for choosing young unrelated donors vs. older sibling donors. Disclosures: No relevant conflicts of interest to declare.

Toxicity, response, and survival in older adults with metastatic melanoma treated with checkpoint inhibitors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 9544-9544
Author(s):  
Nienke A De Glas ◽  
Esther Bastiaannet ◽  
Frederiek van den Bos ◽  
Simon Mooijaart ◽  
Astrid Aplonia Maria Van Der Veldt ◽  
...  
Keyword(s):  
Older Adults ◽  
Overall Survival ◽  
Metastatic Melanoma ◽  
Older Patients ◽  
Regression Models ◽  
Checkpoint Inhibitors ◽  
Performance Status ◽  
Toxicity Response ◽  
Grade 3 ◽  
The Impact

9544 Background: Checkpoint inhibitors have strongly improved survival of patients with metastatic melanoma. Trials suggest no differences in outcomes between older and younger patients, but only relatively young patients with a good performance status were included in these trials. The aim of this study was to describe treatment patterns and outcomes of older adults with metastatic melanoma, and to identify predictors of outcome. Methods: We included all patients aged ≥65 years with metastatic melanoma between 2013 and 2020 from the Dutch Melanoma Treatment registry (DMTR), in which detailed information on patients, treatments and outcomes is available. We assessed predictors of grade ≥3 toxicity and 6-months response using logistic regression models, and melanoma-specific and overall survival using Cox regression models. Additionally, we described reasons for hospital admissions and treatment discontinuation. Results: A total of 2216 patients were included. Grade ≥3 toxicity did not increase with age, comorbidity or WHO performance status, in patients treated with monotherapy (anti-PD1 or ipilimumab) or combination treatment. However, patients aged ≥75 were admitted more frequently and discontinued treatment due to toxicity more often. Six months-response rates were similar to previous randomized trials (40.3% and 43.6% in patients aged 65-75 and ≥75 respectively for anti-PD1 treatment) and were not affected by age or comorbidity. Melanoma-specific survival was not affected by age or comorbidity, but age, comorbidity and WHO performance status were associated with overall survival in multivariate analyses. Conclusions: Toxicity, response and melanoma-specific survival were not associated with age or comorbidity status. Treatment with immunotherapy should therefore not be omitted solely based on age or comorbidity. However, the impact of grade I-II toxicity in older patients deserves further study as older patients discontinue treatment more frequently and receive less treatment cycles.[Table: see text]

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