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•The MAGIC algorithm probability measured at the initiation of second-line therapy for acute GVHD predicts NRM and overall survival.•The higher D28 response rates and survival observed with ruxolitinib than with other therapies were limited to patients with low MAP.

Abnormal pre-transplant pulmonary function tests (PFTs) are associated with reduced survival after allogeneic HCT. Existing scoring systems consider risk dichotomously, attributing risk only to those with abnormal lung function. In a multicenter cohort of 1717 allo-HCT recipients, we examined the association between pre-transplant PFT measures and need for ICU admission (120d), frequency of mechanical ventilation (120d) and overall survival (5 y). Predictive models were developed and validated using Cox proportional hazards, incorporating age, FEV1(forced expiratory volume in 1-second) and diffusing capacity (DLCO). In univariate analysis, hazard ratios for each outcome (95% CI) were: mechanical ventilation (FEV1: 0.60 [0.52–0.69], DLCO: 0.69 [0.61–0.77], p< 0.001), ICU admission (FEV1: 0.74 [0.67–0.82], DLCO: 0.79 [0.72–0.86], p< 0.001) and overall survival (FEV1: HR 0.87 [0.81–0.94], DLCO: 0.83 [0.77–0.89], p< 0.001). A multivariable Cox model was developed and compared to the HCT-CI Pulmonary score in a validation cohort. This model was better at predicting need for ICU admission and mechanical ventilation, while both models predicted overall survival (p< 0.001). In conclusion, the risk conferred by pre-transplant pulmonary function should be considered in a continuous rather than dichotomous manner. A more granular prognostication system can better inform risk of critical care utilization in the early post-HCT period.

•Compared with classic acute GVHD, late acute GVHD presents with worse clinical severity and higher-risk biomarker parameters.•Patients with late acute GVHD have equivalent long-term survival outcomes compared with patients with classic acute GVHD.

•Large pericardial effusion (LPE) and tamponade are purported manifestations associated with atypical chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (alloHCT).•The median time from alloHCT to detection of LPE was 197 days (IQR, 40 to 378 days) in adult alloHCT recipients in our retrospective analysis.•LPE and tamponade necessitate urgent pericardiocentesis or pericardial window placement.•In a multivariable analysis, an HCT Comorbidity Index ≥3 and acute GVHD were risk factors for LPE.•LPE does not cause cardiac damage but results in inferior overall survival.

Hematopoietic stem cell transplantations (HSCT) are intensive and potentially curative modalities available for a variety of hematological diseases. Although alloHSCTs are typically performed in an inpatient setting, there has been increasing interest in moving them to the outpatient setting. AlloHSCTs are associated with a median length of hospital stay of 30 days. AlloHSCTs in the inpatient setting may increase patient exposure to nosocomial infections, drug-resistant organisms, rapid deconditioning with time spent in hospital beds, and loss of muscle mass. In this study, we aim to share outcomes of 856 consecutive alloHSCTs done in our institute over the past 2 decades. This is a single-center retrospective chart review encompassing 856 patients who underwent outpatient alloHSCTs between 2000 and 2017. Reduced-intensity conditioning, stem cell infusion, and much of the immediate follow-up in the early alloHSCT period was performed on an outpatient basis with daily evaluation, laboratory assessment, and intervention as needed. Rate of non-routine hospital admission was our primary outcome of interest. We also looked at various secondary outcomes, including causes of admission, median length of stay, and in-hospital mortality rate. Data analysis was performed using STATA statistical software Version 15. Descriptive statistics were used to summarize baseline demographic data and outcomes. Logistic regression modeling was used to identify predictors of hospital admission. We observed that about one third of our cohort never required admission to the hospital throughout the first 100 days after HSCT. Among those admitted, 6.6% experienced a direct admission to the intensive care unit, and the overall in hospital mortality was low at 5%. Furthermore, the median length of stay was noted to be decreased at 6 days compared to a median reported 30 days in existing literature. Overall, we observed favorable safety profile and outcomes with outpatient management of HSCTs.

The standard primary treatment for acute graft-versus-host disease (GVHD) requires prolonged, high-dose systemic corticosteroids (SCSs) that delay reconstitution of the immune system. We used validated clinical and biomarker staging criteria to identify a group of patients with low-risk (LR) GVHD that is very likely to respond to SCS. We hypothesized that itacitinib, a selective JAK1 inhibitor, would effectively treat LR GVHD without SCS. We treated 70 patients with LR GVHD in a multicenter, phase 2 trial (NCT03846479) with 28 days of itacitinib 200 mg/d (responders could receive a second 28-day cycle), and we compared their outcomes to those of 140 contemporaneous, matched control patients treated with SCSs. More patients responded to itacitinib within 7 days (81% vs 66%, P = .02), and response rates at day 28 were very high for both groups (89% vs 86%, P = .67), with few symptomatic flares (11% vs 12%, P = .88). Fewer itacitinib-treated patients developed a serious infection within 90 days (27% vs 42%, P = .04) due to fewer viral and fungal infections. Grade ≥3 cytopenias were similar between groups except for less severe leukopenia with itacitinib (16% vs 31%, P = .02). No other grade ≥3 adverse events occurred in >10% of itacitinib-treated patients. There were no significant differences between groups at 1 year for nonrelapse mortality (4% vs 11%, P = .21), relapse (18% vs 21%, P = .64), chronic GVHD (28% vs 33%, P = .33), or survival (88% vs 80%, P = .11). Itacitinib monotherapy seems to be a safe and effective alternative to SCS treatment for LR GVHD and deserves further investigation.

Therapy-related myeloid neoplasms (t-MN) are aggressive myeloid neoplasms. Factors predicting post-allogeneic stem cell transplant (alloSCT) survival are not well-known. We studied the prognostic utility of factors at: t-MN diagnosis, pre-alloSCT, and post-alloSCT. Primary endpoints were 3-year overall survival (OS), relapse incidence (RI), and non-relapse mortality (NRM). Post-alloSCT OS did not differ between t-MDS and t-AML (20.1 vs. 19.6 months, P= 1), though t-MDS had a significantly higher 3-year RI compared to t-AML (45.1% vs. 26.9%, P= 0.03). In t-MDS, the presence of monosomy 5 (HR 3.63, P= 0.006) or monosomy 17 (HR 11.81, P= 0.01) pre-alloSCT were associated with higher RI. Complex karyotype was the only factor adversely influencing survival at all the timepoints. The inclusion of genetic information yielded 2 risk-categories: high-risk defined by the presence of pathogenic variants (PV) in (TP53/BCOR/IDH1/GATA2/BCORL1)and standard-risk (remainder of the patients) with 3-year post-alloSCT OS of 0% and 64.6%, respectively (P= 0.001). We concluded that while alloSCT was curative in a subset of t-MN patients, outcomes remained poor, specifically in the high-risk category. t-MDS patients, especially those with persistent disease pre-alloSCT were at increased risk of relapse. Disease-related factors at t-MN diagnosis were the most prognostic of post-alloSCT survival; utility of factors available later in the course, was incremental.

The reduced-intensity conditioning regimen, fludarabine and melphalan, is frequently used in allogeneic hematopoietic stem cell transplantation (HSCT). Melphalan and the active metabolite of fludarabine, F-ara-A, are excreted via the kidneys. Existing methods to assess clearance in this setting are based on serum creatinine, which has known limitations for glomerular filtration rate (GFR) estimation in patients with malignancy. Measured GFR (mGFR) may better predict drug dosing to mitigate toxicity and increase the chances of successful engraftment. The primary objective of this study was to assess the association between mGFR and risk for nonrelapse mortality (NRM) in patients who have undergone allogeneic HSCT receiving conditioning with fludarabine and melphalan. In the 109 included patients, mGFR <65 mL/min/1.73 m2 predicted a significantly higher rate of overall NRM (hazard ratio [HR], 2.13; 95% confidence interval [CI], 1.03-4.35; P = 04) and 1-year incidence of infection (HR, 2.63; 95% CI, 1.54-4.55; P < .001) in addition to a significantly lower 2-year survival (P = .019). Kidney function estimated via estimated GFR (eGFR) and estimated creatinine clearance did not correlate with posttransplant outcomes. These results suggest that mGFR is a promising approach for assessing clearance in patients who have undergone allogeneic HSCT and may be preferred to standard creatinine-based eGFR strategies.

Non-permissive HLA-DPB1 mismatch is associated with increased risk of acute graft versus host disease (GVHD), non-relapse mortality (NRM) and inferior overall survival (OS) in matched unrelated allogenic stem cell transplant (alloSCT) recipients. Post-transplant cyclophosphamide (PTCY) is the new standard GVHD prophylaxis regimen. Here, we describe our experience of DPB1 mismatch including allelic level in patients undergoing unrelated matched (MUD) or mismatched (MMUD) alloSCT with PTCY.

There is data indicating that chronic GVHD has an impact on the central nervous system (CNS-cGVHD). However, leptomeningeal GVHD (LM-cGVHD) is still a rare type of CNS-cGVHD[1]. Here we describe our experience with LM-cGVHD.

Allogeneic stem cell transplant (alloSCT) is considered the therapeutic modality of choice for patients with TP53mutated (TP53mut) myeloid neoplams (MN). However, outcomes remain poor and factors associated with post-alloSCT survival, in this high-risk cohort, are not known.

Wilms tumor mutations (WT)-1 are associated with inferior survival in acute myeloid leukemia (AML); but not considered a high-risk genetic category in the European LeukemiaNet (ELN) guidelines. We compared post-allogeneic stem cell transplant (alloSCT) outcomes of WT1mutAML patients with a known poor prognostic category – TP53mutAML.

Ibrutinib has been studied in steroid-refractory chronic graft vs. host disease (SR-cGVHD), yet the phase II trial that led to FDA approval contained 42 subjects, had restricted organ involvement, and median 2 prior lines of therapy. To expand on this evidence base, we conducted a multi-center real-world study.

Current acute graft-vs-host disease (GVHD) risk stratification systems use either biomarkers (e.g., Ann Arbor scores) or clinical symptoms (e.g., Minnesota risk), but not both. The Minnesota system (standard or high risk) lacks a low risk stratum needed for treatment de-escalation. This MAGIC study had two goals: to determine whether a risk model based on clinical symptoms alone could define three separate groups and to determine whether inclusion of biomarker risks could further improve the prediction of risk. We analyzed 1863 patients who underwent a first HCT for hematological disorders between 2014 – 2021 who received systemic treatment for acute GVHD. We randomly divided them into training (n=1306) and validation (n=557) cohorts so that there were sufficient numbers of patients with less common clinical presentations (e.g. isolated stage 2 or stage 3 GI GVHD) in the training cohort. We divided patients in the training cohort into 15 groups based on clinical similarity and non-relapse mortality (NRM) and then used a classification and regression tree (CART) model to create 3 Manhattan risk groups that were independently confirmed by unsupervised K-means clustering (Table 1). We next compared the Minnesota and Manhattan risk systems in the validation cohort. Half of Minnesota standard risk patients were now categorized as Manhattan low risk and the three Manhattan strata had distinctly different NRM and overall response rates (ORR) to treatment at day 28 (Figure 1). Manhattan risk had a significantly greater area under the receiver operating characteristic curve (AUC) than Minnesota risk in predicting 6-month NRM (0.69 vs. 0.64, P = 0.009). Each Manhattan risk group (low, intermediate, high) was further stratified by Ann Arbor (AA) biomarker scores (1-3) for risk of NRM (data not shown). We again applied a CART analysis to the training cohort to the 9 combinations of Manhattan risk and AA scores to create a new MAGIC risk model of 3 strata that was also confirmed by K-means clustering (Table 2). This analysis only included patients (78%) with serum samples at the time of GVHD treatment initiation. In the validation cohort, the incidence of NRM increased for each successive MAGIC risk group and the ORR decreased accordingly (Figure 2). The AUC of the MAGIC model was greater than the Manhattan model (0.79 vs. 0.70, P = 0.009).

We used a rigorous PRoBE (prospective-specimen collection, retrospective-blinded-evaluation) study design to compare the ability of biomarkers of systemic inflammation and biomarkers of gastrointestinal (GI) tissue damage to predict response to corticosteroid treatment, the incidence of clinically severe disease, 6-month nonrelapse mortality (NRM), and overall survival in patients with acute graft-versus-host disease (GVHD). We prospectively collected serum samples of newly diagnosed GVHD patients (n = 730) from 19 centers, divided them into training (n = 352) and validation (n = 378) cohorts, and measured TNFR1, TIM3, IL6, ST2, and REG3α via enzyme-linked immunosorbent assay. Performances of the 4 strongest algorithms from the training cohort (TNFR1 + TIM3, TNFR1 + ST2, TNFR1 + REG3α, and ST2 + REG3α) were evaluated in the validation cohort. The algorithm that included only biomarkers of systemic inflammation (TNFR1 + TIM3) had a significantly smaller area under the curve (AUC; 0.57) than the AUCs of algorithms that contained ≥1 GI damage biomarker (TNFR1 + ST2, 0.70; TNFR1 + REG3α, 0.73; ST2 + REG3α, 0.79; all P < .001). All 4 algorithms were able to predict short-term outcomes such as response to systemic corticosteroids and severe GVHD, but the inclusion of a GI damage biomarker was needed to predict long-term outcomes such as 6-month NRM and survival. The algorithm that included 2 GI damage biomarkers was the most accurate of the 4 algorithms for all endpoints.

OBJECTIVE--Type 1 and type 2 diabetes are characterized by an ~98 and ~65% loss of pancreatic β-cells, respectively. Efforts to reverse either form of diabetes increasingly focus on the possibility [...]

Multiple Myeloma patients eligible for autologous hematopoietic transplantation (AHT) typically receive 3–6 cycles of induction therapy before transplant. The last induction cycle is completed 2–4 weeks prior to mobilization. We evaluated the impact of the time interval between end of induction and AHT on progression-free survival (PFS) and overall survival (OS). A total of 1055 patients who underwent AHT were identified. The median time to transplant (TTT) was 33 days (27–42 quartile range). Patients with less than 33 days of TTT had significantly prolonged PFS (35.6 vs. 32.1 months, p< 0.03) but non-significant OS differences compared to those with more than 33 days. Quartile comparisons showed that patients in the 1st quartile (less than 27 days) had significantly prolonged PFS (36.7 vs. 30.9 months, p< 0.01) compared to the 4th quartile group (more than 42 days). In a subgroup analysis of patients with partial or worse biochemical response prior to transplant, patients in the 1st quartile had significantly prolonged PFS (37.7 vs. 28.7 months, p< 0.04) compared to the 4th quartile group. In conclusion, we showed that a prolonged TTT is associated with inferior outcomes compared to tighter chemotherapy schedules. This finding was especially prevalent in patients with partial response at induction.

Cytogenetic and molecular abnormalities are known to influence post-transplant outcomes in acute myeloid leukemia (AML) but data assessing the prognostic value of combined genetic models in the HCT setting are limited. We developed an adapted European LeukemiaNet (aELN) risk classification based on available genetic data reported to the Center for International Blood and Marrow Transplant Research, to predict post-transplant outcomes in 2289 adult AML patients transplanted in first remission, between 2013 and 2017. Patients were stratified according to aELN into three groups: favorable (Fav, N= 181), intermediate (IM, N= 1185), and adverse (Adv, N= 923). Univariate analysis demonstrated significant differences in 2-year overall survival (OS) (Fav: 67.7%, IM: 64.9% and Adv: 53.9%; p< 0.001); disease-free survival (DFS) (Fav: 57.8%, IM: 55.5% and Adv: 45.3; p< 0.001) and relapse (Fav: 28%, IM: 27.5% and Adv: 37.5%; p< 0.001). Multivariate analysis (MVA) revealed no differences in outcomes between the Fav and IM groups, thus they were combined. On MVA, patients in the Adv risk group had the highest risk of relapse (HR 1.47 p≤ 0.001) and inferior DFS (HR 1.35 p < 0.001) and OS (HR 1.39 p< 0.001), even using myeloablative conditioning or in those without the pre-HCT measurable-residual disease. Novel approaches to mitigate relapse in this high-risk group are urgently needed.

•Second autologous stem cell transplantation (ASCT) for AL amyloidosis is rarely performed but increasingly being used.•Best outcome to second ASCT is seen after durable remission to ASCT1.•Second ASCT, if chosen, should be used early in the relapse course.•Treatment related mortality can be high, making its choice particularly difficult

Post-allogeneic transplant cytopenias are often multifactorial. Here we describe a case series of patients who presented with agranulocytosis post-transplant during Tacrolimus tapering.

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome is an autoinflammatory condition due to UBA1mutations with limited therapeutic options. Previously, we reported preliminary outcomes on a series of 5 patients with VEXAS treated with allogeneic hematopoietic stem cell transplantation (alloHCT, Mangaonkar A et al. Am J Hematol2023). In this abstract, we present long-term, prospective follow-up data on an expanded cohort of 10 VEXAS patients [including 1 with a haploidentical donor (haploHCT)] treated with alloHCT.

Historically, many transplant (HCT)-eligible patients have not reached HCT due to limited matched donors (especially racial/ethnic minorities) and disease progression. Advances now permit safer use of alternative donors, while best search strategy for a given patient is unclear. The BMT CTN 1702 trial used baseline unrelated donor search prognosis (SP: very likely with 8/8 MUD probability of > 90%, less likely 26% probability, and very unlikely < 10% probability) to guide strategy in a prospective national trial (top line results: similar HCT incidence per SP groups, EBMT 2023). We now share previously unreported data on donor search and selection strategy to achieve HCT, representing an unparalleled comprehensive examination of this process.

Post-transplant Cyclophosphamide (PTCy) is now the standard of care for graft-versus-host disease (GVHD) prophylaxis in patients undergoing allogeneic hematopoietic stem cell transplant (alloHCT). High dose cyclophosphamide, as used in PTCy, is associated with cardiac dysfunction through direct toxicity to myocytes and cardiac endothelium. We hypothesize that patients with cardiac risk factors pre-alloHCT, such as presence of coronary artery calcium (CAC), are at higher risk for non-relapse mortality (NRM) and inferior survival after receiving PTCy for GVHD prophylaxis.

•Black patients have a higher risk of grade III-IV acute GVHD and non-relapse mortality compared to White patients.•MAGIC biomarker scores at the time of treatment effectively stratified the risk of NRM regardless of race.•Black patients with high biomarker scores experienced significantly worse NRM than White patients.

Systems have been put in place in the Mayo Clinic Stem Cell Transplantation program to reduce day-100 all-cause mortality. Currently our mortality has been reduced to 0.3%. Patients can undergo transplant as an outpatient, with a median hospital duration of 0 days and only 25% of patients requiring a hospital stay of 5 days or greater. Outpatient transplantation is safe and reduces patient-incurred costs.

•Pre-alloHCT log2 EASIX score ≥2.32 is associated with increased NRM after PTCy.•The EASIX-HTN model can be used to risk stratify patients receiving PTCy.•Multiorgan failure is a major cause of NRM in patients with high EASIX-HTN score.

•A Manhattan model based solely on clinical symptoms identifies a low-risk group needed to test strategies that minimize treatment.•MAGIC composite scores using both clinical and biomarker parameters further enlarge the low-risk group and most accurately predict outcomes.

1.ST2, REG3α, and/or AREG at the time of acute GVHD diagnosis are excellent predictors of risk for 12-month NRM2.The best biomarker algorithm and threshold for risk stratification may depend on the target population

•Biomarker scores predicted risk of NRM better than clinical severity at the onset of GVHD treatment in children.•A combined biomarker/clinical model was highly sensitive and specific for NRM in children with GVHD.

•A new Mount Sinai model that includes the GVHD grade at start and day 14 of treatment predicts NRM as accurately as the day 28 response.•The MAGIC model, which adds the day 14 MAP to the algorithm, predicts NRM yet more accurately, creating three distinct groups.

1.Flares of acute GVHD following initial clinical response are common and associated with higher NRM.2.MAGIC biomarkers at first complete or very good partial response (CR/VGPR) can predict GVHD flares.

Graft‐versus‐host disease (GVHD), a common complication after peripheral blood stem cell or bone marrow transplantation, rarely occurs in kidney and pancreas transplant recipients. The true incidence may be confounded by the rarity of the disorder, with a resultant lack of appreciation of the diagnosis as a potential cause of common clinical manifestations such as cytopenias and immune dysfunction. Reports of GVHD in kidney and pancreas transplant recipients almost uniformly describe patients in the early posttransplant period (days to months) with the typical manifestations of acute GVHD involving the skin, liver, and intestines. In contrast, reports of solid organ transplant recipients with clinical features more consistent with chronic GVHD (cGVHD) are lacking, raising concern of underrecognition of this severe complication. Occurrence later after transplant may be even more likely to result in lack of recognition. We report 2 cases of possible cGVHD occurring in recipients of pancreas after kidney transplantation, which were diagnosed at 5.5 and 42 months after pancreas transplant. Both patients presented with severe pancytopenia, multiple opportunistic infections, and features suggestive of cGVHD. Transplant professionals should be aware of the possibility of acute and cGVHD in pancreas after kidney transplant recipients and be able to recognize the clinical manifestations. The authors describe 2 cases of fatal chronic graft‐versus‐host disease in pancreas after kidney transplant recipients diagnosed in the setting of severe infections with profound pancytopenia.

•CD20+, Ph-like, and therapy-related ALL are novel high-risk subgroups in adults.•Allogeneic transplantation offsets the poor prognosis associated with these subgroups.•Targeted immunotherapies do not seem to independently predict for post-transplant outcomes.•Maintenance strategies are needed to reduce relapse post-transplant.

Steroid-refractory (SR) acute graft-versus-host disease (GVHD) remains a major cause of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (HCT), but its occurrence is not accurately predicted by pre-HCT clinical risk factors. The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP) identifies patients who are at high risk for developing SR GVHD as early as 7 days after HCT based on the extent of intestinal crypt damage as measured by the concentrations of 2 serum biomarkers, suppressor of tumorigenesis 2 and regenerating islet-derived 3α. We conducted a multicenter proof-of-concept “preemptive” treatment trial of α-1-antitrypsin (AAT), a serine protease inhibitor with demonstrated activity against GVHD, in patients at high risk for developing SR GVHD. Patients were eligible if they possessed a high-risk MAP on day 7 after HCT or, if initially low risk, became high risk on repeat testing at day 14. Thirty high-risk patients were treated with twice-weekly infusions of AAT for a total of 16 doses, and their outcomes were compared with 90 high-risk near-contemporaneous MAGIC control patients. AAT treatment was well tolerated with few toxicities, but it did not lower the incidence of SR GVHD compared with controls (20% vs 14%, P = .56). We conclude that real-time biomarker-based risk assignment is feasible early after allogeneic HCT but that this dose and schedule of AAT did not change the incidence of SR acute GVHD. This trial was registered at www.clinicaltrials.gov as #NCT03459040.

We conducted a retrospective study comparing posttransplant outcomes between myeloma patients receiving conditioning melphalan on day-2 vs day-1 for autologous stem cell transplant. Between January 2017 and December 2018, 201 patients received melphalan on day-2 and 166 on day-1 prior to stem cell infusion. Baseline disease and clinical characteristics between the two groups were similar. Although rates of hospitalization were similar between the cohorts, duration of hospital admission was longer for day-1 (median 7 days for day-1 vs 5 days for day-2, p= 0.003). Rates of fever were higher in the day-1 cohort (69% vs 49%, p= 0.0002). Time to platelet and neutrophil engraftment was significantly longer in the day-1 cohort (platelet engraftment median days 17 for day-1 vs 15 for day-2, p< 0.0001, neutrophil engraftment median days 16 for day-1 vs 16 for day-2, p= 0.025). Overall response rate was similar between the cohorts (99% for day-1, vs 100% for day-2). Day-2 melphalan infusions should be considered in preference for day-1 protocols, given the clinically significant delay in platelet and neutrophil engraftment and longer duration of hospitalization with day-1 infusions.

The graft-versus-leukemia (GVL) effect after allogeneic hematopoietic cell transplant (HCT) can prevent relapse but the risk of severe graft-versus-host disease (GVHD) leads to prolonged intensive immunosuppression and possible blunting of the GVL effect. Strategies to reduce immunosuppression in order to prevent relapse have been offset by increases in severe GVHD and nonrelapse mortality (NRM). We recently validated the MAGIC algorithm probability (MAP) that predicts the risk for severe GVHD and NRM in asymptomatic patients using serum biomarkers. In this study we tested whether the MAP could identify patients whose risk for relapse is higher than their risk for severe GVHD and NRM. The multicenter study population (n= 1604) was divided into two cohorts: historical (2006–2015, n= 702) and current (2015–2017, n= 902) with similar NRM, relapse, and survival. On day 28 post-HCT, patients who had not developed GVHD (75% of the population) and who possessed a low MAP were at much higher risk for relapse (24%) than severe GVHD and NRM (16 and 9%); this difference was even more pronounced in patients with a high disease risk index (relapse 33%, NRM 9%). Such patients are good candidates to test relapse prevention strategies that might enhance GVL.

IMPORTANCE: Allogeneic hematopoietic cell transplant (alloHCT) is known to increase the risk for keratinocyte carcinoma. The extent to which host characteristics, including pigmentary phenotype and UV radiation exposure, contribute is unknown. OBJECTIVE: To identify and validate independent risk factors for keratinocyte carcinoma after alloHCT, including those associated with the transplant and the host. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study analyzed a consecutive sample of alloHCT recipients from January 1, 2000, to December 31, 2014, at the Mayo Clinic, Rochester, Minnesota (n = 872) and University Hospitals Cleveland Medical Center, Cleveland, Ohio (n = 147). Participants from the Mayo Clinic were randomly allocated (2:1) into discovery (n = 581) and validation (n = 291) cohorts. Time to first keratinocyte carcinoma and information about transplant- and host-associated risk factors were extracted. A multivariate keratinocyte carcinoma risk model was created using a stepwise Cox proportional hazards regression model with P ≤ .05 for entry that incorporated all covariates that were individually statistically significant at α = 0.05 in the discovery cohort. The risk model was first internally validated using the Mayo Clinic validation cohort and then externally validated using the independent cohort of alloHCT recipients at University Hospitals Cleveland Medical Center. Data were analyzed from March 13, 2018, to June 12, 2019. EXPOSURES: Allogeneic hematopoietic cell transplant. MAIN OUTCOMES AND MEASURES: The primary outcome was time to development of the first cutaneous keratinocyte carcinoma after alloHCT; secondary outcome, time to development of the first individual basal and/or squamous cell carcinoma after alloHCT. RESULTS: Of the 872 alloHCT recipients identified in the Mayo Clinic cohort (520 men [59.6%]; mean [SD] age, 48.3 [12.6] years), 95 (10.9%) developed keratinocyte carcinoma after alloHCT during 5349 person-years of follow-up. Of the 147 alloHCT recipients in the exernal validation cohort (86 men [58.5%]; mean [SD] age, 47.9 [17.5] years), 18 (12.2%) developed keratinocyte carcinoma after alloHCT in 880 person-years of follow up. Risk factors independently associated with keratinocyte carcinoma after alloHCT included age (hazard ratio [HR] per 10 years, 1.72; 95% CI, 1.21-2.42), chronic lymphocytic leukemia (HR, 2.47; 95% CI, 1.20-5.09), clinically photodamaged skin (HR, 3.47; 95% CI, 1.87-6.41), and history of cutaneous squamous cell carcinoma (HR, 2.60; 95% CI, 1.41-5.91). Harrell concordance statistics were 0.81 (95% CI, 0.72-0.90) and 0.86 (95% CI, 0.74-0.98) for internal and external validation of the keratinocyte carcinoma risk model, respectively. CONCLUSIONS AND RELEVANCE: This study found validated independent risk factors for keratinocyte carcinoma after alloHCT that are enriched with host- compared with transplant-associated risk factors. These findings highlight the importance of assessing host-associated risk factors for keratinocyte carcinoma in patients eligible for alloHCT. Future studies should examine whether keratinocyte carcinoma risk stratification before alloHCT may inform long-term surveillance strategies.