Priyanka A. Pophali

CMV reactivation is associated with a lower incidence of relapse after allo-SCT for CML

Preemptive therapy at CMV reactivation has diminished post-transplant CMV mortality. Furthermore, recent studies suggest a favorable ‘virus-versus-leukemia’ effect from reactivating CMV, reducing relapse of AML after SCT. We studied the relationship of CMV reactivation with leukemic relapse in 110 patients with CML receiving HLA-identical sibling SCT between 1993 and 2008. Of these, 79 (72%) were in chronic phase, 5 in second chronic phase, 17 in accelerated phase and 9 in blast phase. A total of 97 patients (88%) received a myeloablative conditioning regimen, 97 received 4-log ex vivo T cell-depleted grafts and 13 received T-replete grafts. CMV reactivation before day 100 was observed in 72 patients (65.5%). At a median follow-up of 6.2 years, CMV reactivation < day 100 as a time-dependent covariate was an independent factor associated with decreased relapse. We conclude that CMV reactivation may contribute to a beneficial GVL effect in CML transplant recipients.

Male survivors of allogeneic hematopoietic stem cell transplantation have a long term persisting risk of cardiovascular events

Long-term survivors of allogeneic stem cell transplantation (SCT) have increased risk of cardiovascular disease. We retrospectively studied cardiovascular risk factors (CVRFs) in 109 SCT survivors (62 males, 47 females; median age 34 years) five years or more after bone marrow (15) or T cell-depleted peripheral blood (94) SCT for CML (56), acute leukemia (29), MDS (13), and others (11). One death and two cardiovascular events were reported. At five and ten years after SCT, respectively, 44% and 52% had abnormal lipid profiles; 23% of 5-year survivors met the Adult Treatment Panel III threshold for dyslipidemia treatment, which is substantially higher than the age-matched general population. There were significant increases in prevalence of hypertension (p < 0.001), diabetes (p = 0.018), and body mass index (p = 0.044) after SCT compared with baseline. The Framingham general cardiovascular risk score (FGCRS) in males at five years after SCT projected a doubling (median 10.4% vs. 5.4%) in the 10-year risk of cardiovascular events. Females received HRT after SCT, and none had increased FGCRS. Chronic GVHD and C-reactive protein were not associated with CVRF at any time. All CVRFs stabilized between five and ten years after SCT. Thus, SCT survivors have sustained elevations in CVRFs. Males have a significantly increased risk of cardiovascular events in their second and third decade after SCT.

Contrast enhanced cardiac CT reveals coronary artery disease in 45% of asymptomatic allo-SCT long-term survivors.

Contrast enhanced cardiac CT reveals coronary artery disease in 45% of asymptomatic allo-SCT long-term survivors

Repair of Impaired Pulmonary Function Is Possible in Very-Long-Term Allogeneic Stem Cell Transplantation Survivors

Both early- and late-onset noninfectious pulmonary injury are important contributors to the nonrelapse mortality seen after allogeneic stem cell transplantation (allo-SCT), particularly in subjects conditioned with high-dose total body irradiation (TBI). To characterize the kinetics of recovery from pulmonary injury in long-term survivors, we collected data on 138 subjects who survived > 3 years (median survival, 10.2 years) after predominantly TBI-based allo-SCT from their HLA-matched siblings. Baseline pulmonary function tests served as the reference for subsequent measurements at 3, 5, 10, and 15 years for each survivor. The only parameter showing a clinically and statistically significant decline post-transplant was adjusted diffusion capacity of lung for carbon monoxide (DLCO), which reached a nadir at 5 years but surprisingly normalized at the 10-year mark. Multivariable modeling identified chronic graft-versus-host disease (P < .02) and abnormal baseline-adjusted DLCO (P < .03) as the only significant factors associated with the decline in adjusted DLCO at 5 years but excluded smoking, conditioning intensity, baseline C-reactive protein level, TBI dose to the lungs, disease, and demographic variables. In conclusion, pulmonary injury as monitored by the adjusted DLCO continues to deteriorate in the first 5 years after allo-SCT but recovers at 10 years.

Factors influencing the late phase of recovery after bone mineral density loss in allogeneic stem cell transplantation survivors.

Accelerated bone mineral density loss (BMDL) occurs early after allogeneic stem cell transplantation (SCT) and is related to factors such as steroids and chronic GvHD. In order to understand the natural history of BMDL of SCT in the longer term, we evaluated a longitudinal cohort of 148 survivors with a median follow-up of 12 years (range 3–22 years). All women received hormone replacement therapy, and routine calcium/vitamin D supplementation was recommended but ∼50% of patients still had suboptimal vitamin D levels and bisphosphonates were rarely utilized. BMD significantly improved from 5 to 20+ years but the femoral neck and forearm remained vulnerable sites. Younger age, higher pretransplant body mass index (BMI) and increment in BMI post transplant were significantly associated with increased BMD and protected against osteopenia/osteoporosis. These findings support consideration of BMD loss in SCT survivors in two phases, an early phase of BMD loss (3–5 years) followed by a later phase of BMD recovery, with different protective and aggravating factors. Treatment- and transplant-related factors (such as steroids, immunosuppressives, chronic GvHD, vitamin D) are known to impact the early phase of BMD loss but age and BMI are more influential in the late phase of BMD recovery.

Risks factors and timing of genital human papillomavirus (HPV) infection in female stem cell transplant survivors: a longitudinal study

This longitudinal single-center study describes the timing and risk factors for genital human papillomavirus (HPV) disease in women after allogeneic hematopoietic cell transplantation (HCT). Between 1994 and 2014, 109 females underwent HCT of whom 82 surviving transplant for >1 year had regular, comprehensive genital tract assessment and treatment of HPV disease. The cumulative proportions of any genital HPV infection at 1, 3, 5, 10 and 20 years were 4.8%, 14.9%, 28.1%, 36.7% and 40.9%, respectively. Demographic, disease-related factors, chronic GvHD (cGvHD) and its treatment were analyzed for their association with persistent, multifocal or severe genital HPV disease. Pre-transplant HPV disease was strongly associated with any posttransplant HPV (odds ratio (OR)=6.5, 95% confidence interval (CI)=1.65–25.85, P=0.008). Having either extensive or genital cGvHD was associated with increased risk of any HPV disease (OR=5.7, 95% CI=1.90–17.16, P=0.002) and a higher risk for severe genital dysplasia (CIN II–III/VIN II–III; OR=13.1, 95% CI=1.59–108.26, P=0.017), but no one developed HPV-related genital cancer. Persistent, multifocal or severe HPV disease occurred more frequently than in healthy populations. Women with extensive cGvHD, genital cGvHD or pre-transplant HPV are at greatest risk for post-transplant HPV disease. Early initiation of annual screening, comprehensive genital tract assessment and active management are cornerstones of their gynecology care.

Radiation exposure from diagnostic procedures following allogeneic stem cell transplantation – How much is acceptable?

Abstract Background Frequent diagnostic radiology procedures in allogeneic stem cell transplantation (SCT) recipients raise concern about the potential harm from incidental radiation. Objectives To determine the cumulative radiation dose from diagnostic studies in allogeneic SCT and its impact on clinical outcome. Patients and methods This retrospective cohort study was conducted to determine the cumulative radiation dose from diagnostic studies following SCT. Sixty-four consecutive patients with hematological malignancies in a single tertiary care institution underwent total body irradiation (TBI)-based myeloablative conditioning followed by six of six human leukocyte antigen (HLA)-identical sibling allogeneic SCT. The median follow-up was 3 years. The cumulative effective dose in mSv from diagnostic radiological studies in the peri-transplant period from day −30 to day +200 was calculated for each patient and its impact on overall survival and non-relapse mortality was determined. Results The median cumulative radiation exposure from diagnostic radiological procedures was 92 mSv (range 1.2–300), representing about 30× the normal annual background radiation for the population and 10% of the 1200 cGy TBI dose used in conditioning. Sixty-five percent of the cumulative radiation exposure was delivered between day +1 and day 100 and computed tomography scans contributed 88%. In multivariate analysis, diagnostic procedures did not significantly impact clinical outcomes. Conclusions While radiation exposure from diagnostic procedures did not impact clinical outcomes the risk of secondary cancers in long-term survivors is likely to be increased. Our results indicate that patients who are acutely ill for prolonged periods can receive clinically significant radiation doses during their hospital care. Our findings should prompt attempts to limit radiation exposure from diagnostic procedures in post-SCT recipients