Malignant Neoplasms of the Gastrointestinal Tract After Blood or Marrow Transplant.

Importance: Survivors of blood or marrow transplant (BMT) are at increased risk of subsequent malignant neoplasms (SMNs). Cancers of the gastrointestinal (GI) system are of special interest because their clinical behavior is often aggressive, necessitating early detection by increasing awareness of high-risk populations. Objective: To describe the risk of SMNs in the GI tract after BMT. Design, Setting, and Participants: A cohort study of 6710 individuals who lived at least 2 years after BMT performed between January 1, 1974, and December 31, 2014, at City of Hope, University of Minnesota, or University of Alabama at Birmingham. End of follow-up was March 23, 2020. Data analysis was performed between September 1, 2022, and September 30, 2022. Exposures: Demographic and clinical factors; therapeutic exposures before or as part of BMT. Main Outcomes and Measures: Development of SMNs in the GI tract after BMT. Participants self-reported SMNs in the GI tract; these were confirmed with pathology reports, medical records, or both. For deceased patients, death records were used. Standardized incidence ratios determined excess risk of SMNs in the GI tract compared with that of the general population. Fine-Gray proportional subdistribution hazard models assessed the association between risk factors and SMNs in the GI tract. Results: The cohort of 6710 individuals included 3444 (51.3%) autologous and 3266 (48.7%) allogeneic BMT recipients. A total of 3917 individuals (58.4%) were male, and the median age at BMT was 46 years (range, 0-78 years). After 62 479 person-years of follow-up, 148 patients developed SMNs in the GI tract. The standardized incidence ratios for developing specific SMNs ranged from 2.1 for colorectal cancer (95% CI, 1.6-2.8; P < .001) to 7.8 for esophageal cancer (95% CI, 5.0-11.6; P < .001). Exposure to cytarabine for conditioning (subdistribution hazard ratio [SHR], 3.1; 95% CI, 1.5-6.6) was associated with subsequent colorectal cancer. Compared with autologous BMT recipients, allogeneic BMT recipients with chronic graft-vs-host disease were at increased risk for esophageal cancer (SHR, 9.9; 95% CI, 3.2-30.5). Conditioning with etoposide (SHR, 2.0; 95% CI, 1.1-3.5) and pre-BMT anthracycline exposure (SHR, 5.4; 95% CI, 1.3-23.4) were associated with an increased risk of liver cancer compared with no exposure to the respective agents. Conclusions and Relevance: The findings of this cohort study are relevant for oncologists and nononcologists who care for the growing number of survivors of transplant. Awareness of subgroups of survivors of BMT at high risk for specific types of SMNs in the GI tract may influence recommendations regarding modifiable risk factors, as well as individualized screening.

Impact of pre-transplant individual comorbidities on risk of ICU admission and survival outcomes following allogeneic hematopoietic stem cell transplantation.

Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-hsct) can require intensive care unit (ICU) admission in the post-transplant period. Whereas outcomes of ICU admission are poor, little is known about the pre-transplant risk factors leading to them. We conducted a retrospective analysis to investigate the impact of pre-transplant individual comorbidities on acute inpatient complications, focusing on ICU admission, ventilator support and multi-system organ failure, following allo-hsct. During the initial hospitalization, 33 (11%) patients required ICU admission, 29 (10%) required ventilator support and 33 (11%) developed multi-system organ failure. Risk factors for ICU admission and ventilator support included pre-transplant infection, pre-transplant diabetes, time to neutrophil engraftment, donor type and older transplant decade (2008-2010). Risk factors for multi-system organ failure included pre-transplant diabetes, time to neutrophil engraftment and older transplant decade (2008-2010). For ICU patients, the 60-day and 6-month mortality was 58% and 67%, respectively and the median overall survival was 1.4 months. Patients with diabetes and infection at the time of HSCT and longer time to neutrophil engraftment during transplant are at an increased risk for ICU admission, ventilator support and multi-system organ failure. Patients admitted to the ICU are also at a high risk for mortality leading to poor survival.

Combinatorial suicide gene strategies for the safety of cell therapies.

Gene-modified cellular therapies carry inherent risks of severe and potentially fatal adverse events, including the expansion of alloreactive cells or malignant transformation due to insertional mutagenesis. Strategies to mitigate uncontrolled proliferation of gene-modified cells include co-transfection of a suicide gene, such as the inducible caspase 9 safety switch (ΔiC9). However, the activation of the ΔiC9 fails to completely eliminate all gene-modified cells. Therefore, we tested a two suicide gene system used independently or together, with the goal of complete cell elimination. The first approach combined the ΔiC9 with an inducible caspase 8, ΔiC8, which lacks the endogenous prodomain. The rationale was to use a second caspase with an alternative and complementary mechanism of action. Jurkat cells co-transduced to co-express the ΔiC8, activatable by a BB homodimerizer, and the ΔiC9 activatable by the rapamycin analog sirolimus were used in a model to estimate the degree of inducible cell elimination. We found that both agents could activate each caspase independently, with enhanced elimination with superior reduction in cell regrowth of gene-modified cells when both systems were activated simultaneously. A second approach was employed in parallel, combining the ΔiC9 with the RQR8 compact suicide gene. RQR8 incorporates a CD20 mimotope, targeted by the anti-CD20 monoclonal antibody rituxan, and the QBend10, a ΔCD34 selectable marker. Likewise, enhanced cell elimination with superior reduction in cell regrowth was observed when both systems were activated together. A dose-titration effect was also noted utilizing the BB homodimerizer, whereas sirolimus remained very potent at minimal concentrations. Further in vivo studies are needed to validate these novel combination systems, which may play a role in future cancer therapies or regenerative medicine.

Burden of Long-Term Morbidity Borne by Survivors of Acute Myeloid Leukemia Treated With Blood or Marrow Transplantation: The Results of the BMT Survivor Study.

PURPOSE: Blood or marrow transplantation (BMT) is an integral part of consolidation and/or salvage therapy for patients with acute myeloid leukemia (AML). With the growing population of AML survivors, there is a need to understand the quality of their survival. MATERIALS AND METHODS: This multisite study included 1,369 2-year survivors who underwent BMT for AML between 1974 and 2014 at age ≥ 21 years and 1,310 siblings. Using Common Terminology Criteria for Adverse Events, severe/life-threatening and fatal chronic health conditions were identified. Multivariable regression analysis was used to compare the risk of severe/life-threatening conditions and health status between survivors and siblings, and to identify risk factors for health conditions among BMT survivors. RESULTS: The prevalence of severe/life-threatening conditions was 54.9% in BMT survivors compared with 28.5% in siblings (P < .001), yielding 3.8-fold higher odds of severe/life-threatening conditions (95% CI, 3.1 to 4.7) among the BMT survivors. The most prevalent conditions included subsequent neoplasms, diabetes, cataracts, venous thromboembolism, and joint replacement. Survivors were more likely to report poor general health (odds ratio [OR], 3.8; 95% CI, 2.8 to 5.1), activity limitation (OR, 3.7; 95% CI, 3.0 to 4.5), and functional impairment (OR, 2.9; 95% CI, 2.3 to 3.6). Among BMT recipients, the 20-year cumulative incidence of severe/life-threatening/fatal conditions was 68%. History of chronic graft-versus-host disease was associated with a higher risk of pulmonary disease (hazard ratio [HR], 3.1; 95% CI, 1.0 to 9.3), cataract (HR, 2.6; 95% CI, 1.4 to 3.8), and venous thromboembolism (HR, 2.3; 95% CI, 1.3 to 4.7). Relapse-related mortality (RRM) plateaued at 30%, whereas non-RRM increased to 50% at 30 years. CONCLUSION: The burden of severe/life-threatening conditions is substantially higher in BMT recipients when compared with an unaffected comparison group, contributing to an increasing incidence of non-RRM over time. Chronic graft-versus-host disease was an important risk factor for severe/life-threatening/fatal conditions among BMT recipients, informing the need for close monitoring to anticipate and manage morbidity.

Tumor lysis syndrome and infectious complications during treatment with venetoclax combined with azacitidine or decitabine in patients with acute myeloid leukemia.

Venetoclax (Ven) in combination with azacitidine or decitabine (hypomethylating agent; HMA) is the standard-of-care treatment for older (≥75 years) or intensive chemotherapy ineligible adults with newly diagnosed acute myeloid leukemia (AML). Tumor lysis syndrome (TLS) and infectious complications are two of the most concerning associated adverse events. We studied the real-world incidence and outcomes of these adverse events with HMA/Ven in AML patients. Our retrospective analysis included 106 patients (median age 70 years). Of these, 61 (58%) received HMA/Ven in frontline setting while 45 (42%) received in salvage setting. 19 (18%) met laboratory criteria for TLS, five (5%) developed clinical TLS (acute kidney injury). The median time to develop TLS was 2 days (range -2 to 4). During cycle 1, 29 patients (27%) were diagnosed with febrile neutropenia while 26 (25%) developed new infections. Median time to development of new infection was 10 days (1-25). Pneumonia was the most common infection (8%). Febrile neutropenia and/or new infection during cycle 1 was associated with poorer median overall survival compared to those without these complications (4.9 months vs 11.6 months; p = 0.03). In conclusion, incidence of TLS and infections was high in our cohort during initiation of HMA/Ven therapy. This data emphasizes the need for closer monitoring in these patients, especially during the first 7-10 days of treatment, which is often achieved in the inpatient setting.

Trends in Late Mortality and Life Expectancy After Autologous Blood or Marrow Transplantation Over Three Decades: A BMTSS Report.

PURPOSE: We determined trends in life expectancy and cause-specific late mortality after autologous blood or marrow transplantation (BMT) performed over a 30-year period, using the BMT Survivor Study. METHODS: We constructed a cohort of 4,702 individuals with hematologic neoplasms who lived ≥ 2 years after autologous BMT performed between 1981 and 2014 at three transplant centers. The end of follow-up was April 19, 2021. The primary exposure variable was autologous BMT performed in four eras: 1981-1999; 2000-2005; 2006-2010; and 2011-2014. Vital status and cause of death were obtained from National Death Index Plus program and Accurinct databases. RESULTS: The median age at BMT was 53 years (range, 0-78 years), 58.7% were male, 67.8% were non-Hispanic White, and 28.3% had undergone transplantation between 2011 and 2014. Autologous BMT recipients experienced a 7-year reduction in life expectancy. The adjusted hazard of 5-year all-cause mortality declined over the four eras (reference: 1981-1999; hazard ratio [HR]2000-2005 = 0.77; 95% CI, 0.62 to 0.94; HR2006-2010 = 0.64; 95% CI, 0.51 to 0.79; HR2011-2014 = 0.56; 95% CI, 0.45 to 0.71; Ptrend < .001), as did years of life lost (5.0 years to 1.6 years). The reduction in all-cause mortality was most pronounced among those transplanted for Hodgkin lymphoma or plasma cell dyscrasias, but was not observed among those transplanted for non-Hodgkin lymphoma or those conditioned with total-body irradiation. We also observed a decline in late deaths because of infection (Ptrend < .0001; primarily for BMTs before 2006) and subsequent neoplasms (Ptrend = .03; confined to decline in therapy-related myeloid neoplasm-related mortality) but not because of cardiovascular or renal disease. CONCLUSION: Late mortality among autologous BMT recipients has declined over a 30-year period. However, ongoing efforts are needed to mitigate development of infections, subsequent neoplasms, and cardiovascular and renal disease to further reduce late mortality.

Conditioning intensity and probability of live birth after blood or marrow transplantation, a BMTSS report.

We examine the impact of conditioning intensity (low intensity: nonmyeloablative/reduced intensity vs high intensity: myeloablative) and total body irradiation (TBI) on the probability of live birth after blood or marrow transplantation (BMT). Study participants were drawn from the BMT Survivor Study (BMTSS) and included 1607 transplant survivors between 1974 and 2014 at age ≤45 years, with survival ≥2 years post-BMT and age at study ≥18 years. Closest-age, same-sex biologic siblings (n = 172) were 1:1 matched with 172 survivors. Survivors and siblings self-reported information on sociodemographic, chronic health conditions, and pregnancies. Within survivor analysis: the association between the primary exposure variable (no TBI/low-intensity conditioning; 200 to 800 cGy TBI/low-intensity conditioning; no TBI/high-intensity conditioning; >800 cGy TBI/high-intensity conditioning) and the odds of no post-BMT live birth were examined using multivariable logistic regression, adjusting for clinical and demographic variables. Median age at BMT was 31 years (IQR, 0 to 45), and median length of follow-up was 14.3 years (IQR, 2.4 to 41.4); 39.3% were autologous BMT recipients, and 46.6% were female. Overall, 120 (8.7%) survivors reported post-BMT live births. Receipt of >800 cGy TBI/high-intensity conditioning (odds ratio [OR], 3.7; 95% CI, 1.9-7.0; ref: no TBI/low-intensity conditioning) was associated with higher odds of reporting no live birth post-BMT. In contrast, 200 to 800 cGy TBI/low-intensity conditioning (OR, 1.3; 95% CI, 0.5-3.3), and no TBI/high-intensity conditioning (OR, 0.9; 95% CI, 0.5-1.7) were at similar risk of reporting post-BMT live birth as no TBI/low-intensity conditioning. Comparison with biologic siblings: Using conditional logistic regression, we found that BMT survivors were more likely to report no live birth (OR, 2.0; 95% CI, 1.2-3.3) compared with siblings. These findings could inform conditioning intensity options for patients wishing to preserve fertility post-BMT.

Trends in Late Mortality and Life Expectancy After Allogeneic Blood or Marrow Transplantation Over 4 Decades: A Blood or Marrow Transplant Survivor Study Report.

IMPORTANCE: The past 4 decades have seen substantial changes in allogeneic blood or marrow transplantation (BMT) practice, with the overarching goal of expanding the eligible patient pool while optimizing disease-free survival. OBJECTIVE: To determine trends in life expectancy and cause-specific late mortality after allogeneic BMT performed over a 40-year period. DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study of 4741 individuals who lived 2 or more years after allogeneic BMT performed between January 1, 1974, and December 31, 2014, was conducted at City of Hope, University of Minnesota, or University of Alabama at Birmingham. The end of follow-up was March 23, 2020. EXPOSURES: Allogeneic BMT performed in 3 eras: 1974-1989, 1990-2004, and 2005-2014. MAIN OUTCOMES AND MEASURES: All-cause, recurrence-related, and nonrecurrence-related mortality and projected reduction in life expectancy. Information regarding vital status and cause of death was obtained from the National Death Index Plus and Accurint databases. RESULTS: Of the 4741 individuals included in the study, 2735 (57.7%) were male; median age at BMT was 33 years (range, 0-75 years). The cumulative incidence of recurrence-related mortality plateaued at 10 years, reaching 12.2% (95% CI, 11.0%-13.4%) at 30 years from BMT. In contrast, the incidence of nonrecurrence-related mortality continued to increase and was 22.3% (95% CI, 20.4%-24.3%) at 30 years. Leading causes of nonrecurrence-related mortality included infection (30-year cumulative incidence, 10.7%; standardized mortality ratio [SMR], 52.0), subsequent malignant neoplasms (30-year cumulative incidence, 7.0%; SMR, 4.8), cardiovascular disease (30-year cumulative incidence, 4.6%; SMR, 4.1), and pulmonary disease (30-year cumulative incidence, 2.7%; SMR, 13.9). Compared with the general population, the relative mortality remained higher at 30 or more years after BMT (SMR, 5.4; 95% CI, 4.0-7.1). The cohort experienced a 20.8% reduction in life expectancy (8.7 years of life lost). Compared with 1974-1989 (reference), the adjusted 10-year hazard ratio (HR) of all-cause mortality declined over the 3 eras (1990-2004: HR, 0.67; 95% CI, 0.53-0.85; 2005-2014: HR, 0.52; 95% CI, 0.39-0.69; P < .001 for trend), as did years of life lost (1974-1989: 9.9 years [reference]; 1990-2004: 6.5 years; and 2005-2014: 4.2 years). The reduction in late mortality was most pronounced among individuals who underwent transplantation at ages younger than 18 years (1990-2004: HR, 0.62; 95% CI, 0.40-0.96; 2005-2014: HR, 0.30; 95% CI, 0.16-0.54; reference: 1974-1989; P < .001 for trend) and those who received bone marrow (1990-2004: HR, 0.70; 95% CI, 0.54-0.90; 2005-2014: HR, 0.45; 95% CI, 0.29-0.69; reference: 1974-1989; P < .001 for trend). CONCLUSIONS AND RELEVANCE: This cohort study noted that late mortality among recipients of allogeneic BMT has decreased over the past 40 years; however, life expectancy was not restored to expected rates compared with the general US population. Furthermore, the reduction in risk of late mortality appeared to be confined to those who underwent transplantation at a younger age or those who received bone marrow. Further efforts to mitigate disease recurrence, infections, subsequent neoplasms, cardiovascular disease, and pulmonary disease may be useful in this population.

Impact of access to care on 1-year mortality following allogeneic blood or marrow transplantation.

Mortality is highest in the first year following an allogeneic hematopoietic stem cell transplant. With recent advancements, we have expanded the pool of patients to whom we are able to offer transplant as a treatment option. In this context, we analyzed socioeconomic, patient, disease and transplant-related variables that predicted for 1-year all-cause, relapse-related (RRM) and non-relapse related mortality (NRM) in 304 patients at the University of Alabama at Birmingham. The 1-year overall survival, RRM and NRM rates were 60.5%, 13.5% and 22.7% respectively. A KPS score < 80, pre-transplant infection and hypertension and non-complete remission disease status adversely effected all-cause mortality. For NRM, increasing age, pre-transplant infection and diabetes, and poor access to care were associated with higher mortality whereas haploidentical donor type was associated with improved survival. For RRM, a KPS score <80, high/very high disease risk index and the presence of comorbidities were risk factors for higher mortality. Poor access to care, in addition to individual comorbidities, performance status and high-risk disease characteristics, is associated with adverse outcomes following transplant. We propose the incorporation of socioeconomic variables with patient, disease, and transplant-related variables to predict 1-year NRM.

Total Body Irradiation and Risk of Breast Cancer After Blood or Marrow Transplantation: A Blood or Marrow Transplantation Survivor Study Report.

PURPOSE: To examine the association between total body irradiation (TBI) and subsequent breast cancer in women treated with blood or marrow transplantation (BMT) for hematologic malignancies. PATIENTS AND METHODS: Participants were drawn from the BMT Survivor Study (BMTSS), a retrospective cohort study that included patients who underwent transplantation between 1974 and 2014 and survived for ≥ 2 years after BMT. Patients with pre-BMT chest radiation or a history of breast cancer were excluded. Participants completed the BMTSS survey, which included details regarding breast cancer diagnosis. Subsequent breast cancer was confirmed by pathology report review or physician notes. Cox proportional hazards models assessed the association between TBI and subsequent breast cancer. Standardized incidence ratios were calculated to determine the excess risk of subsequent breast cancer compared with that in the general population. RESULTS: A total of 1,464 female BMT survivors (allogeneic: n = 788; autologous: n = 676) participated, with a median follow-up of 9.3 years from BMT. TBI was used in 660 patients (46%). Thirty-seven women developed subsequent breast cancer (allogeneic: n = 19; autologous: n = 18). Multivariable analysis revealed that exposure to TBI was associated with an increased risk of subsequent breast cancer among allogeneic BMT survivors (hazard ratio [HR], 3.7 [95% CI, 1.2 to 11.8]; P = .03) and autologous BMT survivors (HR, 2.6 [95% CI, 1.0 to 6.8]; P = .048). Pre-BMT exposure to alkylating agents was associated with an increased risk of subsequent breast cancer among autologous BMT survivors (HR, 3.3 [95% CI, 1.0 to 9.0]; P = .05). Compared with that in the general population, exposure to TBI at age < 30 years was associated with a 4.4-fold higher risk of subsequent breast cancer in allogeneic BMT survivors and a 4.6-fold higher risk in autologous BMT survivors. CONCLUSION: The association between TBI and subsequent breast cancer, especially among those exposed at a young age, as well as pre-BMT exposure to alkylating agents, should inform breast cancer screening for early detection.

Clinicopathological and molecular characteristics of extramedullary acute myeloid leukaemia.

AIMS: Myeloid sarcoma (MS) is a rare extramedullary neoplasm composed of immature myeloid precursor cells thought to be a unique clinical presentation of acute myeloid leukaemia (AML). Like AML, MS has a poor prognosis, but due to the rare nature of MS there are limited studies examining potential prognostic factors. We report our institutional experience, with the aim of investigating and establishing salient clinicopathological and molecular features of MS. METHODS AND RESULTS: We retrospectively examined all clinicopathological and molecular data on MS patients between 2001 and 2017 from the University of Alabama at Birmingham (UAB) electronic medical records. The UAB electronic medical records were also reviewed and compared with the literature for other potential prognostic factors. Sixty-three patients were included in the study. The median overall survival was 24 months in the group with normal karyotype and 12 months in patients with an abnormal karyotype. CONCLUSIONS: We found that an abnormal karyotype was associated with a statistically significant worse prognosis.

Mobilization of Hematopoietic Progenitor Cells for Autologous Transplantation Using Pegfilgrastim and Plerixafor: Efficacy and Cost Implications.

Filgrastim (FIL) is the most common growth factor combined with plerixafor for autologous hematopoietic progenitor cell mobilization, but requires daily, multi-injection administration. We adopted a standardized mobilization regimen with pegfilgrastim (PEG) and upfront plerixafor, allowing for a single injection given the long half-life and slow elimination of PEG. Between 2015 and 2017, a total of 235 patients with lymphoma or plasma cell dyscrasias underwent mobilization with PEG 6 mg on day 1 and upfront plerixafor 24 mg on day 3, followed by apheresis on day 4 regardless of peripheral blood CD34+ cells. The median CD34+ cells/mm3 in peripheral blood on first day of collection was 48 and median collection yield was 7.27 × 106 CD34+ cells/kg (range, 0.32 to 39.6 × 106 CD34+ cells/kg) after a mean of 1.6 apheresis collections. Overall, 83% of patients achieved the mobilization target, and 95% reached the minimum necessary CD34+ cell yield to proceed with transplantation (2 × 106 CD34+ cells/kg). Because FIL is weight-based and dosed daily, the cost comparison with PEG is influenced by patient weight and number of apheresis sessions required. A cost simulation using actual patient data indicates that PEG is associated with lower cost than FIL for the majority of patients. Autologous hematopoietic progenitor cell mobilization with PEG and plerixafor is practical, effective, and not associated with increased cost compared with FIL mobilization.

Assessment of Late Mortality Risk After Allogeneic Blood or Marrow Transplantation Performed in Childhood.

Importance: Allogeneic blood or marrow transplantation (BMT) is a curative option for malignant and nonmalignant diseases of childhood. However, little is known about trends in cause-specific late mortality in this population during the past 3 decades. Objectives: To examine cause-specific late mortality among individuals who have lived 2 years or more after allogeneic BMT performed in childhood and whether rates of late mortality have changed over time. Design, Setting, and Participants: A retrospective cohort study was conducted of individuals who lived 2 years or more after undergoing allogeneic BMT performed in childhood between January 1, 1974, and December 31, 2010. The end of follow-up was December 31, 2016. Exposure: Allogeneic BMT performed in childhood. Main Outcomes and Measures: All-cause mortality, relapse-related mortality, and non-relapse-related mortality. Data on vital status and causes of death were collected using medical records, the National Death Index Plus Program, and Accurint databases. Results: Among 1388 individuals (559 females and 829 males) who lived 2 years or more after allogeneic BMT performed in childhood, the median age at transplantation was 14.6 years (range, 0-21 years). In this cohort, there was a total of 295 deaths, yielding an overall survival rate of 79.3% at 20 years after BMT. The leading causes of death were infection and/or chronic graft-vs-host disease (121 of 244 [49.6%]), primary disease (60 of 244 [24.6%]), and subsequent malignant neoplasms (45 of 244 [18.4%]). Overall, the cohort had a 14.4-fold increased risk for death (95% CI, 12.8-16.1) compared with the general population (292 deaths observed; 20.3 deaths expected). Relative mortality remained elevated at 25 years or more after BMT (standardized mortality ratio, 2.9; 95% CI, 2.0-4.1). The absolute excess risk for death from any cause was 12.0 per 1000 person-years (95% CI, 10.5-13.5). The cumulative incidence of non-relapse-related mortality exceeded that of relapse-related mortality throughout follow-up. The 10-year cumulative incidence of late mortality decreased over time (before 1990, 18.9%; 1990-1999, 12.8%; 2000-2010, 10.9%; P = .002); this decrease remained statistically significant after adjusting for demographic and clinical factors (referent group: <1990; 1990-1999: hazard ratio, 0.64; 95% CI, 0.47-0.89; P = .007; 2000-2010: hazard ratio, 0.49; 95% CI, 0.31-0.76; P = .002; P < .001 for trend). Conclusions and Relevance: Late mortality among children undergoing allogeneic BMT has decreased during the past 3 decades. However, these patients remain at an elevated risk of late mortality even 25 years or more after transplantation when compared with the general population, necessitating lifelong follow-up.

Two Cases and a Review of Graft-Versus-Host Disease and the Role of Hepatitis C Treatment in Liver Transplant Patients.

Graft-versus-host disease (GvHD) is a rare but fatal complication after solid organ transplantation arising in 1% to 2% of cases. We report 2 cases of GvHD after orthotopic liver transplantation. Both patients had a history of hepatitis C virus (HCV) infection prior to transplantation. Both cases presented between 1 and 4 months after transplantation with rash, pancytopenia, and/or diarrhea. Our second case also developed oral and ocular manifestations after liver transplantation, which are more commonly described after stem cell transplantation. Diagnosis in both cases was made by clinical presentation in conjunction with histopathology and flow cytometry. Both patients were treated by increasing immunosuppression with tacrolimus and high-dose steroids. Response to treatment differed based on the degree of pancytopenia. Our case report is distinguished by several factors such as the context of GvHD presentation and the role of HCV treatment. Diagnosis of GvHD is difficult and often delayed due to nonspecific presentation that overlaps with other conditions. Furthermore, the relation between HCV treatment and potential initiation of GvHD in solid organ transplant patients is unclear.