Hashmi, Shahrukh K.

The severe acute respiratory syndrome coronavirus 2, which causes COVID-19, has now spread to many countries, has forced health care systems to minimise or even suspend access to specialist services for many patients because of social distancing policies. As a result of this, many patients are not in direct, face-to-face contact with their health care specialist. This can pose a challenge, since patients who have undergone haematopoietic cell transplant can suffer from an array of complications involving various organs in the body, such as inactivity-related deconditioning and fatigue, resulting in poor quality of life. These vulnerable patients must receive continuous and individualised rehabilitation guidance to help prevent deterioration and promote optimal functioning. This paper highlights the potential challenges for patients who have had haematopoietic cell transplant in the circumstances surrounding COVID-19 and proposes service development ideas to help reduce the negative impact on patients' quality of life.

Abstract Comparative outcomes of allogeneic hematopoietic cell transplantation (HCT) for BCR-ABL1− myeloproliferative neoplasms (MPNs) in blast phase (MPN-BP) vs de novo acute myeloid leukemia (AML), and AML with prior myelodysplastic syndromes (MDSs; post-MDS AML), are unknown. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we compared HCT outcomes in 177 MPN-BP patients with 4749 patients with de novo AML, and 1104 patients with post-MDS AML, using multivariate regression analysis in 2 separate comparisons. In a multivariate Cox model, no difference in overall survival (OS) or relapse was observed in patients with MPN-BP vs de novo AML with active leukemia at HCT. Patients with MPN-BP in remission had inferior OS in comparison with de novo AML in remission (hazard ratio [HR], 1.40 [95% confidence interval [CI], 1.12-1.76]) due to higher relapse rate (HR, 2.18 [95% CI, 1.69-2.80]). MPN-BP patients had inferior OS (HR, 1.19 [95% CI, 1.00-1.43]) and increased relapse (HR, 1.60 [95% CI, 1.31-1.96]) compared with post-MDS AML. Poor-risk cytogenetics were associated with increased relapse in both comparisons. Peripheral blood grafts were associated with decreased relapse in MPN-BP and post-MDS AML (HR, 0.70 [95% CI, 0.57-0.86]). Nonrelapse mortality (NRM) was similar between MPN-BP vs de novo AML, and MPN-BP vs post-MDS AML. Total-body irradiation–based myeloablative conditioning was associated with higher NRM in both comparisons. Survival of MPN-BP after HCT is inferior to de novo AML in remission and post-MDS AML due to increased relapse. Relapse-prevention strategies are required to optimize HCT outcomes in MPN-BP.

BackgroundMultiple myeloma (MM) with the translocation t(11;14) may have inferior outcomes in comparison with other standard‐risk MM, and it has been suggested to portend a worse prognosis in African Americans in comparison with Whites. This study used the Center for International Blood and Marrow Transplant Research (CIBMTR) database to examine the impact of t(11;14) on the clinical outcomes of patients with MM of African American and White descent.MethodsThis study evaluated 3538 patients who underwent autologous hematopoietic cell transplantation (autoHCT) for MM from 2008 to 2016 and were reported to the CIBMTR. Patients were analyzed in 4 groups: African Americans with t(11;14) (n = 117), African Americans without t(11;14) (n = 968), Whites with t(11;14) (n = 266), and Whites without t(11;14) (n = 2187).ResultsAfrican Americans with t(11;14) were younger, had lower Karnofsky scores, and had more advanced stage MM with a higher Hematopoietic Cell Transplantation–Comorbidity Index (HCT‐CI). Fewer African Americans with t(11;14) (21%) had a coexistent high‐risk marker in comparison with Whites with t(11;14) (27%). In a multivariate analysis, race and t(11;14) had no association with progression‐free survival. However, overall survival was superior among African Americans with t(11;14) in comparison with Whites with t(11;14) (hazard ratio, 0.53; 95% confidence interval, 0.30‐0.93; P = .03). Survival was also associated with female sex, stage, time from diagnosis to transplant, a low HCT‐CI, and receipt of maintenance.ConclusionsRace may have a differential impact on the survival of patients with t(11;14) MM who undergo autoHCT and needs to be further studied.

BackgroundUpfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults.MethodsThe authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression‐free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value <.01 was considered to be statistically significant a priori.ResultsAn increase in AHCT was noted in 2017 (28%) compared with 2013 (15%) among patients aged ≥70 years. Although approximately 82% of patients received melphalan (Mel) at a dose of 200 mg/m2 overall, 58% of the patients aged ≥70 years received Mel at a dose of 140 mg/m2. On multivariate analysis, patients aged ≥70 years demonstrated no difference with regard to NRM (hazard ratio [HR] 1.3; 99% confidence interval [99% CI], 1‐1.7 [P = .06]), REL (HR, 1.03; 99% CI, 0.9‐1.1 [P = 0.6]), PFS (HR, 1.06; 99% CI, 1‐1.2 [P = 0.2]), and OS (HR, 1.2; 99% CI, 1‐1.4 [P = .02]) compared with the reference group (those aged 60‐69 years). In patients aged ≥70 years, Mel administered at a dose of 140 mg/m2 was found to be associated with worse outcomes compared with Mel administered at a dose of 200 mg/m2, including day 100 NRM (1% [95% CI, 1%‐2%] vs 0% [95% CI, 0%‐1%]; P = .003]), 2‐year PFS (64% [95% CI, 60%‐67%] vs 69% [95% CI, 66%‐73%]; P = .003), and 2‐year OS (85% [95% CI, 82%‐87%] vs 89% [95% CI, 86%‐91%]; P = .01]), likely representing frailty.ConclusionsThe results of the current study demonstrated that AHCT remains an effective consolidation therapy among patients with MM across all age groups.

AbstractTransplant‐associated thrombotic microangiopathy (TA‐TMA) has a wide range of presentations after hematopoietic stem‐cell transplantation (HSCT). We retrospectively studied the risk factors and outcomes of patients with early (≤day 100) and late (>day 100) TA‐TMA. Among the 1451 HSCT recipients, early TA‐TMA occurred in 45 (3.1%) patients at a median of 27 (3‐91) days, and late TA‐TMA in 39 (2.7%) patients at a median of 303 (122‐2595) days. Patients with early TA‐TMA were more likely to have high blood calcineurin‐inhibitor levels (P < .001) and acute graph‐vs‐host disease (GVHD, P < .001), while late TMA patients were more likely to have chronic GVHD (P < .001). The estimated median overall survival after onset of TMA for the entire cohort was 6 months. The estimated median overall survival was not reached in patients with an improvement of TMA vs 2 months in patients with no improvement (P < .001). In the early TMA group, older age (for every 10 years, HR 1.40; 95% CI 1.00‐1.94; P = .049) and bacterial infection (HR 2.42; 95% CI 0.98‐6.00; P = .056) were positively associated with mortality. Switching to MMF treatment (HR 0.40; 95% CI 0.16‐0.99; P = .047) and improvement of TMA (HR 0.08; 95% CI 0.03‐0.25; P < .001) were negatively associated with mortality in the multivariate analysis. In the late TMA group, the improvement of TMA was the only independent predictor associated with a lower risk of death (HR 0.05; 95% CI 0.02‐0.19; P < .001). Mortality rates in both early and late TMA remain unacceptably high. Future studies are needed for early diagnosis, trigger identifications, and use of targeted treatments.

Abstract Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P &lt; .0001; DIPSS-Int-2 and higher: HR, 0.39, P &lt; .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P &lt; .0001; DIPSS-Int-2 and higher: HR, 2.55, P &lt; .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.

Abstract Background: Disparities in MM survival among different racial groups persist despite improvements in overall survival (OS). We report a comprehensive review of the SEER Medicare database to elucidate the causes of differences in disease presentation, management practices, cost of care and their relationships to outcomes among the MM patients (pts) from different racial groups. Methods: Pts diagnosed with MM between 1991-2010 with continuous Medicare coverage (1 year prior to diagnosis-date of death/end of 2012) were included. MM complications (MM-C); hypercalcemia (C), renal dysfunction (R), anemia (An), bone fractures (B), dialysis (D) occurring prior to/within 30 days of MM diagnosis (at diagnosis; AT-D), or any time later (after diagnosis; AF-D) were summarized. Demographics, survival (PEDSAF files) and disease characteristics, drug/stem cell transplant (SCT) utilization (NCH, OUTSAF, PDESAF files) were obtained. Trends in incidence of MM-C, treatment type over time (proportional odds) and their association with race (logistic regressions) were compared. Associations between race, MM-C AT-D and MM related death using Fine and Gray's competing risk methods were analyzed. Medicare claims adjusted for inflation (2013) within the first 6 months (mth)/total MM care were summed by drug and total charges. Median cost of care by race and year of diagnosis were evaluated by Kruskal-Wallis (univariate) and proportional odds models (multivariate). Results: A total of 35842 pts (52.1% males) with median age of 76 yr (range 18-104) were included. Mutually exclusive racial subgroups were: White (W, 72%), Hispanic (H: 7.3%), African-American (AA, 16.2%), Asian (A, 4.1%), other (0.3%). A significantly increasing trend in the prevalence of all MM-C AT-D was seen over time (all p<0.001). For AF-D, all MM-C initially increased but decreased from 2006-2010 except D that showed continued increase (Fig 1A). For race, MM-C were significantly different, with AA having the most C, R, An and D while W having the most B (Fig 1B). Inferior OS was seen with male gender (p=0.006), increasing age, earlier years of diagnosis, belonging to W or H race, C, R and B (all p<0.001), but not with An (p=0.298) or D (p=0.378). Trends in OS over time showed a significant interaction with race in 1991-1995 (p<0.001), 1996-2000 (p=0.004) and 2001-2005 (p<0.001) but not in 2006-2010 (p=0.182), possibly due to shorter follow up. Medicare claims analysis showed that pts receiving any treatment increased from 12.8% in 1991-1995 to 59.3% in 2006-2010 (p<0.001). Specific therapy utilization, including SCT and all drug classes/agents evaluated increased except for cytotoxic chemotherapy utilization (melphalan/cyclophosphamide), which decreased (Fig 2A). Any therapy utilization was significantly different by race (p<0.001) with highest for H (36.5%) and lowest for AA (31.6%). Specific treatments differed significantly by race (Fig 2B). Cost of care analysis showed significant increase over years for median drug claims (0.23k to 3.63k) and total claims (5.11k to 27.8k) during first 6 mth as well as for any time after MM diagnosis (drug: 1.3k to 9.9k, total: 21.9k to 84k) (p<0.001 for all). Median drug claims in first 6 mth were highest among AA (1.3k) and lowest among A (0.63k) (p<0.001). Same was true for total claims in first 6 mth (p<0.001). For any time after diagnosis, H had the highest drug (p<0.001) and total (p=0.081) claims. There were significant interactions between year of diagnosis, race and cost of care with H seeing the highest increase in drug claims in first 6 mth (p<0.001) and any time (p=0.002). Conclusion: MM-C have generally decreased AF-D due to improved therapeutics although AA continue to have the highest rates of MM-C. Our data shows that utilization and cost of MM care have increased tremendously with resulting improved outcomes, but significant racial disparities persist. These disparities may be in part due to impaired access to new agents from lack of supplemental insurance for certain racial groups. Drug utilization and cost of care disparities may also be due to differences in co-morbidities, MM-C or access leading to differential healthcare utilization and should be explored in order to ameliorate disparities in outcomes. Disclosures Ailawadhi: Pharmacyclics: Consultancy; Novartis: Consultancy; Amgen Inc: Consultancy; Takeda Oncology: Consultancy.