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Elevated pretransplant serum ferritin levels have been associated with an increased incidence of morbidity and mortality after allogeneic haematopoietic stem cell transplantation (HCT). We studied 222 patients who underwent myeloablative allogeneic HCT in whom pretransplantation serum ferritin levels were available. Pretransplantation ferritin > 1910 μg/l was associated with lower overall survival ( P = 0·003), lower relapse-free survival ( P = 0·003), decreased chronic graft- versus-host disease (GVHD) ( P = 0·019) and increased non-relapse mortality (NRM) ( P = 0·042). Similar results were obtained when pretransplantation ferritin was analysed as a continuous variable and by quartiles. Our results indicate that an elevated pretransplant ferritin level adversely impacts transplantation outcomes. The adverse impact of elevated ferritin on NRM and survival was despite its association with lower incidences of acute and chronic GVHD, which are major causes of NRM. The association of ferritin with iron overload and its influence on HCT outcomes requires further prospective validation. [ABSTRACT FROM AUTHOR]

Patient readmission within 30 days from discharge has been perceived by the Centers for Medicare and Medical Services as an indicator of poor healthcare quality for specific high-cost medical conditions. Patients who undergo allogeneic hematopoietic cell transplantation (allo-HCT) are often being readmitted. Our study identified the risk factors for 30-day readmission among 618 adult recipients of myeloablative allo-HCT from 1990 to 2009. Two hundred forty-two (39%) of 618 patients (median age = 42 years [range: 18-66]) were readmitted a median of 10 days (range: 1-30) from their hospital discharge. Median duration of readmission was 8 days (range: 0-103). Infections (n = 68), fever with or without identified source of infection (n = 63), gastrointestinal complications (n = 44), graft-versus-host disease (GVHD) (n = 38), and other reasons (n = 29) accounted for 28%, 26%, 18%, 16%, and 12% of readmissions, respectively. During their index admission, patients who were subsequently readmitted had more documented infections (P < .001), higher hematopoietic cell transplantation comorbidity index (HCT-CI) (P < .01), total body irridiation (TBI)-based conditioning (P < .001), unrelated donor (P < .001), and peripheral stem cell (P = .014) transplantation. In multivariable analysis, HCT-CI (odds ratio [OR] = 1.78; 95% confidence interval [CI], 1.25-2.52), TBI-based preparative regimen (OR = 2.63; 95% CI, 1.67-4.13), and infection during admission for allo-HSCT (OR = 2.00; 95% CI, 1.37-2.92) predicted 30-day readmission. Thirty-day readmission itself was an independent predictor of all-cause mortality (hazard ratio [HR]Adj = 1.66; 95% CI, 1.36-2.10). Our data emphasize the importance of a risk-standardized approach to 30-day hospital readmission if it is used as a quality-of-care metric for bone marrow transplantation. [ABSTRACT FROM AUTHOR]

Vitamin D (VD) deficiency can cause osteomalacia, bone pain, muscle weakness, fatigue, and increased risk of fracture, and may precipitate or exacerbate osteopenia and osteoporosis. Patients receiving treatment for acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL) may have limited exposure to sunlight and often experience gastrointestinal side effects that may decrease their ability to maintain an adequate VD level. We hypothesized that patients with AML and ALL would have a low VD level after allogeneic hematopoietic cell transplant (HCT), and that these patients would have a high incidence of osteoporosis/osteopenia. We therefore studied the incidence of low VD level and low bone mineral density after HCT. Of 289 patients with AML or ALL undergoing HCT between January 1, 2000, and January 31, 2009, at the Cleveland Clinic, 58 (20.1%) patients had VD testing after HCT. Of these, 52 (89.7%) patients had a low VD level, and 6 (10.3%) had a normal level. Most patients with VD testing had graft-versus-host disease (GVHD) and were taking corticosteroids (94.8% and 98.3%, respectively). Of the 49 patients with VD testing who also had bone mineral density testing, 65% had abnormal (low bone density) results. Only 21% of patients with VD testing were taking VD supplements prior to testing, and 65% had an elevated parathyroid hormone level. We found that most patients did not have VD testing after HCT, but those that did were very likely to have a low level and have low bone mineral density. Those with a low VD level were likely to have received corticosteroids, have GVHD, and have an elevated parathyroid hormone (PTH) level. Given the potential morbidity of low VD level, VD deficiency should be considered after HCT. Prospective study of VD level and its impact on morbidity and mortality after HCT is warranted. [Copyright &y& Elsevier]

Allogeneic hematopoietic stem cell transplantation (SCT) for patients who have previously undergone allogeneic or autologous SCT is potentially curative, but dangerous. To identify patient, disease, and treatment characteristics associated with outcome, we analyzed prognostic factors in 98 consecutive patients who underwent second transplants using allogeneic donors at the Cleveland Clinic between May 1987 and October 2008. Inclusion criteria included age ≥18 years, first SCT either autologous or allogeneic, and second SCT allogeneic. Patients whose second transplant was myeloablative (MA) had shorter survival (median 3.2 versus 14.7 months, P < .001) than patients whose second transplant was nonmyeloablative (NMA). In multivariable analysis, MA second transplant was associated with a higher risk of NRM (hazard ratio [HR] 2.01, P = 0.022) and death (HR 2.13, P = 0.002). Improved survival after NMA second transplant occurred primarily in patients without acute leukemia and when the first transplant was allogeneic. Among 17 patients transplanted within 3 months of first transplant, mortality was 100% and median survival was 2.3 months. MA transplantation within 3 months of prior SCT carries an unacceptably high rate of NRM. NMA second transplants were associated with substantially less NRM and despite a higher incidence of relapse, significantly improved survival compared to MA second transplants. [Copyright &y& Elsevier]

Relapse is the most frequent cause of treatment failure after allogeneic hematopoietic cell transplantation (alloHCT). While transplant-related mortality has decreased substantially over the last few decades, little progress has been made in outcomes and no standard of care exists for patients (pts) with post-alloHCT relapse. In the recent era, several new therapies, including targeted agents, have been approved for ALL, AML, and MDS. We conducted a study to evaluate outcomes of pts with these diseases who relapse after alloHCT in the contemporary period with routine availability of these newer therapeutic agents. We performed a single-institution retrospective cohort study to review treatment strategies and outcomes of relapse post-alloHCT. We identified 420 adults who received their first alloHCT in 2010-2018 using any conditioning regimen or donor source. Overall, 115 (27%) pts experienced relapse (ALL=17/64 [27%], AML=67/242 [28%], MDS=31/114 [27%]) and were included in the analysis. Myeloablative (54%) matched-unrelated donor grafts (50%) were the most common types of HCTs. Peripheral blood stem cell graft (49%) and bone marrow graft (48%) were used the most. Median time from alloHCT to relapse was 5 (range 1-65) months, and 83% of relapses occurred within the first year. Only 24% and 11% of pts experienced grade II-IV acute and any chronic graft-versus-host disease (GVHD) prior to relapse, respectively. Seven of 17 pts had Ph+ ALL. Mutation panel was tested in 56% of AML and MDS. Median follow-up period after relapse was 19 (range 6-80) months. The estimated survival after relapse is shown in figure 1. Table 1 summarizes the treatments used for relapse after alloHCT. Targeted therapy was associated with a trend towards better survival compared to other therapies (Fig 2, HR 0.65, 95% CI 0.41-1.03, p=0.06). Matched unrelated (vs. matched sibling, HR 1.70, p=0.027) or haploidentical donor grafts (HR 2.69, p=0.003), presence of grade II-IV acute GVHD before relapse (HR 2.46, p<0.001), and <12 months from HCT to relapse (<6 vs. >12 months, HR 6.34, p<0.001; 6-12 vs. >12 months, HR 3.16, p=0.005) were adverse prognostic features with survival after relapse post-alloHCT (Table 2). Outcomes of pts with ALL, AML, and MDS who relapse following alloHCT remain poor in the contemporary era when several newer therapies, including targeted agents, are available for their treatment. Targeted agents were used only in a minority of post-alloHCT relapses likely due to the combination of pt status, absence of the target mutation, the agents' availability, and other factors. Pts who developed grade II-IV acute GVHD and had shorter "disease-free" duration from unrelated or haploidentical donor grafts had the significantly shorter survival following relapse. More innovative treatment strategies to prevent and treat relapse post-alloHCT are needed. [ABSTRACT FROM AUTHOR]

PROs are increasingly used in HCT to capture symptoms, quality of life, and functional status. At the Cleveland Clinic, PROs are systematically collected prior to ambulatory visits and used in routine clinical care to identify patients (pts) with distress in real-time through a data capture initiative called the "Knowledge Program." Instruments include the Patient Health Questionnaire (PHQ-9), National Comprehensive Cancer Network Distress Thermometer (DT), and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Health (PH) and Mental Health (MH) assessments. There are limited data on the use of these instruments in the HCT population. We evaluated these PRO measures in HCT recipients and their association with post-HCT outcomes. We identified 292 adult pts undergoing first allogeneic HCT from 2015-2018. Of those, 257 had at least one PRO assessment and were included in this analysis. Time intervals evaluated were: pre-HCT (within 3 months [mos]), 0-6 mos, 6-12 mos, 1-2 years (yrs), and 2-5 yrs post HCT. PHQ-9 assesses depression and categorized as minimal (score 0-4), mild (5-9), moderate (10-14), moderately severe (15-19), and severe (20-27). Higher DT scores indicate more distress and categorized as mild (0-3), moderate (4-7), severe (8-10). Lower scores on PROMIS indicate poorer PH or MH respectively. We evaluated PRO data descriptively for each time interval. Pre-HCT scores were analyzed for association with grade 2-4 acute graft-versus-host disease (GVHD), relapse, non-relapse mortality (NRM), and survival. Figure 1 shows boxplots for mean PHQ-9 and DT scores pre- and post-HCT. Mean scores for the PHQ-9 ranged from 1.1 ± 2.4 (SD) occurring >2 yrs post-HCT to 2.4 ± 3.0 pre-HCT. Mean DT scores were overall low, with highest distress (2.0 ± 2.2) seen pre-HCT. Mean scores for PH and MH were similar at each time intervals, with means ranging 47-48 for PH and 49-51 for MH. Higher PHQ-9 pre-HCT was associated with higher NRM (HR 1.21, 95% CI 1.09-1.34, P<0.001) and worse overall mortality (HR 1.12, 95% CI 1.02-1.23, P=0.016). Higher PROMIS PH and MH scores were associated with lower NRM (HR 0.49, 95% CI 0.26-0.94, P=0.031 and HR 0.28, 95% CI 0.14-0.56, P<0.001), respectively. DT scores had no associations with any outcome. Pts who developed acute GVHD had significantly higher PHQ-9 scores (mean 2.8 vs 1.9, P=0.014), PROMIS-PH (mean 45 vs 49, P=0.029) and MH scores (mean 47 vs 52, P=0.011) relative to those who did not have acute GVHD. PROs such as the PHQ-9, DT, and PROMIS have important clinical utility in allogeneic HCT recipients. Routine clinical use of these assessments not only help identify pts with high levels of distress or depression in real-time, they also demonstrate prognostic value for post-HCT survival outcomes. [ABSTRACT FROM AUTHOR]

Abstract: Results were analyzed for 48 consecutive patients with acute myeloid leukemia not in remission who underwent unrelated donor bone marrow or stem cell transplantation between 1991 and February 2003 at 2 transplant centers. Forty-six were adults with a median age of 32 years (range, 4-58 years). Forty-two were HLA-A, -B, and -DR matched with their respective donors, and 6 were mismatched at 1 of these loci. The conditioning regimen was myeloablative in all cases: busulfan/cyclophosphamide/etoposide in 34 patients, busulfan/cyclophosphamide in 10 patients, and total body irradiation based in 4 patients. Median follow-up for survivors was 540 days (range, 145-2716 days). Only patients with <5000 peripheral blood blasts per microliter at the time of transplantation survived 2 years (18% versus 0%; P = .003). Similarly, patients with <20% blasts in the marrow at the time of transplantation had superior 2-year survival compared with those who had ≥20% (33% versus 5%; P = .04). Patients with <20% blasts who had ≥3 prior therapies also fared poorly. Cause of death was more commonly treatment related rather than relapse related. This study confirms that patients with acute myeloid leukemia not in remission can achieve prolonged survival with myeloablative conditioning and unrelated donor cell transplantation. However, sustained survival occurs only in patients with a low disease burden at the time of unrelated donor stem cell transplantation, and patients with a high disease burden may benefit from added counseling regarding the high risk of death due to both treatment-related toxicities and disease relapse. [Copyright &y& Elsevier]

Advances in allogeneic hematopoietic cell transplantation (HCT) have led to significantly improved day 100 survival over time. Longer-term (≥1 year) survival, however, has not changed significantly. In an effort to improve outcomes and identify patients (pts) at higher risk for 1-year mortality, we created a day 100 risk assessment tool. The Day 100 Risk Assessment tool includes 11 items: HCT-co-morbidity index, distance from transplant center, performance status (PS) at day 100, GVHD requiring systemic corticosteroids, infection requiring intravenous antimicrobials, caregiver support, poor coping skills/motivation, substance abuse, poor health literacy/access, medication compliance, and "other" concerns from the care team. Pts were given a point for each identified factor and categorized as low risk (score 0-2) or high risk (score≥3). High risk pts were targeted for closer follow up beyond 100 days. Cox regression was used to identify risk factors for overall survival (OS) within the first year after HCT. Between 11/2015-6/2018, 208 pts underwent allogeneic HCT and 161 pts survived without relapse at day 100 (Table). Median follow up is 12 months (range 3-33). 1-year OS for low-risk pts was significantly better than for high-risk pts (82% vs 68%, P=0.006; Figure). Multivariable analysis accounting for both pre-transplant and Day 100 risk factors identified older age (≥55), (HR 2.92, 95% CI 1.21-7.08, P=0.017); high disease risk (HR 2.93, 95% CI 1.34-6.39, P=0.007), and day 100 high-risk score (HR 2.29, 95% CI 1.17-4.48, P=0.015) as significant factors for poor OS. Univariate analysis of individual components of the day 100 risk score identified poor PS at day 100, infection, and caregiving concerns as significant variables, P<0.004. A second multivariable model including individual factors demonstrated that poor PS (HR 2.68, P=0.013), infection (HR 2.57, P=0.009) and older age (HR 2.55, P=0.041) remained significantly associated with poor OS. In sum, we developed a Day 100 Risk Assessment tool and identified factors occurring within the first 100 days beyond traditional pre-transplant variables which significantly impact longer-term outcome. Targeted close follow up of these higher risk pts may help to improve survival of this at-risk population. [ABSTRACT FROM AUTHOR]