Nandita Khera

Economics of hematopoietic cell transplantation

Given the rapidly rising healthcare costs, it is important to understand the economic costs of hematopoietic cell transplantation (HCT), a procedure that is being used more frequently in the treatment of various hematologic disorders. Studies have reported a wide range of costs for HCT, from

Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation: A Report from the Center for International Blood and Marrow Transplant Research

36 000 to

Validation of measurement scales in ocular graft-versus-host disease

88 000 (USD) for a single autologous transplantation for the initial hospitalization, to

Nonmalignant late effects and compromised functional status in survivors of hematopoietic cell transplantation

200 000 (USD) or more for a myeloablative allogeneic procedure involving an unrelated donor. Common posttransplantation complications, such as infections and GVHD, have been shown to be significant cost drivers. Comparisons across studies are limited by differences in patient populations, cost ascertainment methods, and length of follow-up. This article summarizes the current state of knowledge about costs and cost-effectiveness of HCT, highlighting the challenges in conducting these studies and identifying important areas for future research. We discuss the need for more value-based assessments of HCT using high-quality approaches to measuring costs and outcomes so that potential future efforts to contain costs are well informed and appropriate.

Secondary solid cancer screening following hematopoietic cell transplantation.

Although transplant practices have changed over the last decades, no information is available on trends in incidence and outcome of chronic graft-versus-host disease (cGVHD) over time. This study used the central database of the Center for International Blood and Marrow Transplant Research (CIBMTR) to describe time trends for cGVHD incidence, nonrelapse mortality, and risk factors for cGVHD. The 12-year period was divided into 3 intervals, 1995 to 1999, 2000 to 2003, and 2004 to 2007, and included 26,563 patients with acute leukemia, chronic myeloid leukemia, and myelodysplastic syndrome. Multivariate analysis showed an increased incidence of cGVHD in more recent years (odds ratio = 1.19, P < .0001), and this trend was still seen when adjusting for donor type, graft type, or conditioning intensity. In patients with cGVHD, nonrelapse mortality has decreased over time, but at 5 years there were no significant differences among different time periods. Risk factors for cGVHD were in line with previous studies. This is the first comprehensive characterization of the trends in cGVHD incidence and underscores the mounting need for addressing this major late complication of transplantation in future research.

Influence of Conventional Cardiovascular Risk Factors and Lifestyle Characteristics on Cardiovascular Disease After Hematopoietic Cell Transplantation

PURPOSE To validate measurement scales for rating ocular chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation. Candidate scales were recommended for use in clinical trials by the National Institutes of Health (NIH) Chronic GVHD Consensus Conference or have been previously validated in dry eye syndromes. DESIGN Prospective follow-up study. PARTICIPANTS Between August 2007 and June 2010, the study enrolled 387 patients with chronic GVHD in a multicenter, prospective, observational cohort. METHODS Using anchor-based methods, we compared clinician or patient-reported changes in eye symptoms (8-point scale) with calculated changes in 5 candidate scales: The NIH eye score, patient-reported global rating of eye symptoms, Lee eye subscale, Ocular Surface Disease Index, and Schirmer test. Change was examined for 333 follow-up visits where both clinician and patient reported eye involvement at the previous visit. Linear mixed models were used to account for within-patient correlation. MAIN OUTCOME MEASURES An 8-point scale of clinician or patient-reported symptom change was used as an anchor to measure symptom changes at the follow-up visits. RESULTS In serial evaluations, agreement regarding improvement, stability, or worsening between the clinician and patient was fair (weighted kappa = 0.34). Despite only fair agreement between evaluators, all scales except the Schirmer test correlated with both clinician-reported and patient-reported changes in ocular GVHD activity. Among all scales, changes in the NIH eye scores showed the greatest sensitivity to symptom change reported by clinicians or patients. CONCLUSIONS Our results support the use of the NIH eye score as a sensitive measure of eye symptom changes in clinical trials assessing treatment of chronic GVHD.

Reporting and Grading Financial Toxicity

PURPOSE Our objective was to describe the incidence of nonmalignant late complications and their association with health and functional status in a recent cohort of hematopoietic cell transplantation (HCT) survivors. PATIENTS AND METHODS We determined the incidence of 14 nonmalignant late effects in adults who underwent transplantation from January 2004 through June 2009 at Fred Hutchinson Cancer Research Center who survived at least 1 year after HCT. Data were derived from review of medical records and annual self-reported questionnaires. RESULTS The 1,087 survivors in the study had a median age at HCT of 53 years (range, 21 to 78 years) and were followed for a median of 37 months (range, 12 to 77 months) after HCT. The prevalence of pre-existing conditions ranged from 0% to 9.8%. The cumulative incidence of any nonmalignant late effect at 5 years after HCT was 44.8% among autologous and 79% among allogeneic recipients; 2.5% of autologous and 25.5% of allogeneic recipients had three or more late effects. Survivors with three or more late effects had lower physical functioning and Karnofsky score, lower likelihood of full-time work or study, and a higher likelihood of having limitations in usual activities. Predictors of at least one late effect were age ≥ 50 years, female sex, and unrelated donor, but not the intensity of the conditioning regimen. CONCLUSION The burden of nonmalignant late effects after HCT is high, even with modern treatments and relatively short follow-up. These late effects are associated with poor health and functional status, underscoring the need for close follow-up of this group and additional research to address these complications.

Second Solid Cancers after Allogeneic Hematopoietic Cell Transplantation Using Reduced-Intensity Conditioning

Hematopoietic stem cell transplant (HCT) recipients have a substantial risk of developing secondary solid cancers, particularly beyond 5 years after HCT and without reaching a plateau overtime. A working group was established through the Center for International Blood and Marrow Transplant Research and the European Group for Blood and Marrow Transplantation with the goal to facilitate implementation of cancer screening appropriate to HCT recipients. The working group reviewed guidelines and methods for cancer screening applicable to the general population and reviewed the incidence and risk factors for secondary cancers after HCT. A consensus approach was used to establish recommendations for individual secondary cancers. The most common sites include oral cavity, skin, breast and thyroid. Risks of cancers are increased after HCT compared with the general population in skin, thyroid, oral cavity, esophagus, liver, nervous system, bone and connective tissues. Myeloablative TBI, young age at HCT, chronic GVHD and prolonged immunosuppressive treatment beyond 24 months were well-documented risk factors for many types of secondary cancers. All HCT recipients should be advised of the risks of secondary cancers annually and encouraged to undergo recommended screening based on their predisposition. Here we propose guidelines to help clinicians in providing screening and preventive care for secondary cancers among HCT recipients.

Factors associated with adherence to preventive care practices among hematopoietic cell transplantation survivors

PURPOSE To determine the influence of modifiable lifestyle factors on the risk of cardiovascular disease after hematopoietic cell transplantation (HCT). PATIENTS AND METHODS HCT survivors of ≥ 1 year treated from 1970 to 2010 (n = 3,833) were surveyed from 2010 to 2011 on current cardiovascular health and related lifestyle factors (smoking, diet, recreational physical activity). Responses (n = 2,362) were compared with those from a matched general population sample (National Health and Nutrition Examination Survey [NHANES]; n = 1,192). RESULTS Compared with NHANES participants, HCT survivors (median age, 55.9 years; median 10.8 years since HCT; 71.3% allogeneic) had higher rates of cardiomyopathy (4.0% v 2.6%), stroke (4.8% v 3.3%), dyslipidemia (33.9% v 22.3%), and diabetes (14.3% v 11.7%; P < .05 for all comparisons). Prevalence of hypertension was similar (27.9% v 30.0%), and survivors were less likely to have ischemic heart disease (6.1% v 8.9%; P < .01). Among HCT survivors, hypertension, dyslipidemia, and diabetes were independent risk factors for ischemic heart disease and cardiomyopathy, and smoking was associated with ischemic heart disease and diabetes (odds ratios [ORs], 1.8 to 2.1; P = .02). Obesity was a risk factor for post-transplantation hypertension, dyslipidemia, and diabetes (ORs ≥ 2.0; P < .001). In contrast, lower fruit/vegetable intake was associated with greater risk of dyslipidemia and diabetes (ORs, 1.4 to 1.8; P ≤ .01), and lower physical activity level was associated with greater risk of hypertension and diabetes (ORs, 1.4 to 1.5; P < .05). Healthier lifestyle characteristics among HCT survivors attenuated risk of all cardiovascular conditions assessed. CONCLUSION Attention of clinicians to conventional cardiovascular risk factors and modifiable lifestyle characteristics offers hope of reducing serious cardiovascular morbidity after HCT.

A randomized phase II crossover study of imatinib or rituximab for cutaneous sclerosis after hematopoietic cell transplantation

DOI: 10.1200/JCO.2014.57.8740 In my hematology-oncology practice, I often see the worry and burden of financial concerns when patients share their stories with me, looking for comfort or tangible help investigating their financial options. I imagine other patients whisper to their families and friends instead, not wanting to influence my treatment recommendations by injecting such considerations into the discussion. I suspect I ought to ask all patients about financial vulnerabilities. After all, shouldn’t it be part of my full review of symptoms? Maybe it is not quite in the same league as shortness of breath, fevers, new neurologic symptoms, or fatigue. Or is it? Ms R is a 59-year-old woman diagnosed with a second primary breast cancer with axillary lymph node involvement 3 years ago. She had a bilateral mastectomy followed by adjuvant chemotherapy and radiation and at least three lines of endocrine therapy and chemotherapy for repeated local recurrences. Currently she is being treated with everolimus and exemestane. Her out-of-pocket expenses (from deductibles and copayments for office visits and prescriptions) have been increasing exponentially since her diagnosis to the point where she has spent close to