Health‐related quality of life following haematopoietic cell transplantation: patient education,evaluation and intervention

Health‐related quality of life (QOL) is a vital concern in the pre‐treatment consent process and post‐treatment care of recipients of haematopoietic cell transplantation (HCT). We propose that comprehensive care of such patients requires an integration of knowledge of the impact of HCT on QOL, assessment of QOL, as well as resources available for intervention. This knowledge may significantly improve patient care when incorporated into daily clinical practice in the transplant setting. As a framework for this approach, this article reviews the literature on QOL after allogeneic and autologous HCT for adults with haematological malignancies. We then discuss evidence in support of the beneficial impact of clinical QOL assessment, and finally evaluate behavioural interventions that show promise to maintain or improve QOL after HCT.     

The polyomavirus puzzle: is host immune response beneficial in controlling BK virus after adult hematopoietic cell transplantion?

BK virus (BKV), a ubiquitous human polyomavirus, usually does not cause disease in healthy individuals. BKV reactivation and disease can occur in immunosuppressed individuals, such as those who have undergone renal transplantation or hematopoietic cell transplantation (HCT). Clinical manifestations of BKV disease include graft dysfunction and failure in renal transplant recipients; HCT recipients frequently experience hematuria, cystitis, hemorrhagic cystitis (HC), and renal dysfunction. Studies of HCT patients have identified several risk factors for the development of BKV disease including myeloablative conditioning, acute graft‐versus‐host disease, and undergoing an umbilical cord blood (uCB) HCT. Although these risk factors indicate that alterations in the immune system are necessary for BKV pathogenesis in HCT patients, few studies have examined the interactions between host immune responses and viral reactivation in BKV disease. Specifically, having BKV immunoglobulin‐G before HCT does not protect against BKV infection and disease after HCT. A limited number of studies have demonstrated BKV‐specific cytotoxic T cells in healthy adults as well as in post‐HCT patients who had experienced HC. New areas of research are required for a better understanding of this emerging infectious disease post HCT, including prospective studies examining BK viruria, viremia, and their relationship with clinical disease, a detailed analysis of urothelial histopathology, and laboratory evaluation of systemic and local cellular and humoral immune responses to BKV in patients receiving HCT from different sources, including uCB and haploidentical donors.     

Predictive value of risk assessment scores in patients with hematologic malignancies undergoing reduced‐intensity conditioning allogeneic stem cell transplantation

Reduced‐intensity conditioning allogeneic stem cell transplantation (RIC allo‐SCT) is associated with less toxicity and is used for older patients. We retrospectively studied the predictive value of two risk assessment scores, which were the hematopoietic cell transplantation‐specific comorbidity index (HCT‐CI) and the pre‐transplantation assessment of mortality (PAM) score, for assessing the outcome of RIC allo‐SCT. Seventy‐eight patients underwent transplantation between 2005 and 2013 at a single institution. RIC was performed with fludarabine and melphalan with/without total body irradiation. The 3‐year overall survival of patients with an HCT‐CI >3 was significantly worse than that of patients with an HCT‐CI 0–3 (31.6% vs. 59.6%, P = 0.020). Also, the 3‐year overall survival of patients with a PAM score >24 was significantly worse than that of those with a PAM score ≤24 (29.2% vs. 61.4%, P = 0.005). The present findings suggest that changing the cut‐off values of these risk assessment scores can improve prediction of outcomes in patients receiving RIC allo‐SCT with this conditioning regimen and we need validation by large‐scale study with other regimens. Am. J. Hematol. 89:E138–E141, 2014. © 2014 Wiley Periodicals, Inc.     

Allogeneic stem cell transplantation for sickle cell disease. A study of patients' decisions

Allogeneic stem cell transplantation is increasingly considered as a curative though risky treatment option for adults with sickle cell disease. Little is known about attitudes of adult patients and their health care providers regarding the risks and benefits of transplantation. A survey of 100 patients and their health care providers was undertaken. Assessment of risk was by a reference gamble paradigm. Comparison was made of the characteristics of those accepting substantial risk vs those not accepting risk, as well as assessment of agreement on risks recommended by health care providers and accepted by patients. Sixty-three of 100 patients were willing to accept some short-term risk of mortality in exchange for the certainty of cure. Fifteen patients were willing to accept more than 35% mortality risk. No differences in patient or disease-related variables were identified between those accepting risk and those not accepting risk. There was no agreement between the recommendations of health care providers and the risk accepted by patients. A substantial proportion of adults with sickle cell disease are interested in curative treatment, at the expense of considerable risk. The decision to accept risk is influenced by individual patient values that cannot be easily quantified and that do not correlate with the assessment of the health care provider. Given the substantial interest in curative therapy, education about and consultation for allogeneic stem cell transplantation in sickle cell patients should be encouraged.     

Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation

Haematopoietic stem cell transplantation (HCT) is the treatment of choice for defined malignant and non-malignant haematological disorders. The main drawbacks of HCT are early transplant-related mortality and late complications, which interfere with patient outcome, health status and quality of life. In comparison with other post-transplant complications, cardiac or cardiovascular consequences seem to occur at a much lower frequency. Early complications are usually associated with patient history before transplantation, primary diagnosis, age of the patient and associated comorbidities, and the type of transplantation and conditioning used. Late cardiac and cardiovascular events may occur years and even decades after HCT, and are related to cardiotoxic chemotherapy, mediastinal radiation therapy, gender, age at transplantation, cardiovascular risk factors and graft-versus-host disease in allogeneic HCT. As has been observed in long-term survivors of Hodgkin lymphoma, where the incidence of cardiovascular complications emerged as a significant problem with increasing follow-up, it is anticipated that the incidence of these complications after HCT will also increase significantly with increasing follow-up of the survivors. This review presents the available data on early and late cardiac and cardiovascular consequences after HCT, and presents recommendations for cardiac assessment and management of these complications.     

Pulmonary function testing prior to hematopoietic stem cell transplantation

The pretransplant pulmonary function test plays an important role in the management of noninfectious pulmonary complications after hematopoietic stem cell transplantation (HCT). Although these tests are widely used as standard preoperative assessments in the nontransplant population, common conditions associated with the HCT patient requires that particular attention be given to interpretation of pulmonary function testing (PFT) results, such as comparison of serial pulmonary function tests and evaluation of the diffusion capacity. Although their utility in helping to predict the likelihood of developing post transplant pulmonary complications and mortality is not well established, current data indicate that pretransplant PFTs are important as a reference for the interpretation of post transplant PFTs and for identifying patients at high risk for developing pulmonary complications and/or mortality after HCT. Future studies of pretransplant pulmonary function should consider the advances in HCT, so that pretransplant PFTs will become a useful tool in pretransplant risk assessment and help the transplant oncologist to determine the most appropriate conditioning regimen for a patient with compromised lung function.     

Hematopoietic cell transplantation for patients with myelodysplastic syndromes (MDS): When,how and for whom?

Hematopoietic cell transplantation (HCT) offers potentially curative therapy for patients with myelodysplastic syndromes (MDS). However, who should and can be transplanted, with which approach, and when is a matter of debate. Various classification schemes and prognostic scoring systems have helped in the decision-making process. Offering HCT to patients who were not considered transplant candidates in the past is now possible with the development of new transplant strategies. In addition to disease stage, patient age, comorbid conditions, preHCT chemotherapy, type of donor, source of stem cells, and possibly other factors, need to be considered prior to transplant. Patients without substantial comorbid conditions up to 60 years with the availability of unrelated donor grafts or 65 years with related donor grafts can be transplanted with more conventional (higher dose) regimens (e.g. targeted BU/CY; Flu/BU). Older patients and patients with comorbid conditions should be enrolled in trials aimed at optimizing RIC/nonmyeloablative HCT (e.g. Flu/melphalan; Flu/low dose TBI). Patients who present with 'advanced' MDS or are transfusion dependent, and do not have a del(5q), should probably be transplanted early in their course. GVHD (in all patients) and post-HCT relapse (in patients with high risk disease) remain major problems. Modifications of transplant conditioning regimens have reduced transplant-related mortality and allow successful HCT even in older patients. However, prospective randomized trials are needed to determine the role of pre-HCT chemotherapy and the type of transplant conditioning regimen best suited for a given patient.     

Impact of hematopoietic stem cell transplantation in patients with relapsed or refractory mantle cell lymphoma

Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) still have a poor prognosis, and the choice between high-dose therapy with autologous hematopoietic cell transplantation (HCT) and allogeneic HCT remains controversial in these patients. We retrospectively analyzed the risk factors for outcomes in 162 R/R MCL patients who received autologous (n?=?111) or allogeneic (n?=?51) HCT between 2004 and 2014. The median overall survival (OS) rates were 48 and 65 months in the autologous and allogeneic HCT groups, respectively (P?=?0.20). Significant risk factors for overall survival in R/R MCL patients after autologous HCT were >?60 years of age at HCT (P?=?0.017), higher score of HCT-specific comorbidity index at HCT (P?=?0.033), and receiving MCEC (ranimustine?+?carboplatin?+?etoposide?+?cyclophosphamide) regimen (P?=?0.017), while higher performance status at HCT (P?=?0.011) and longer interval from diagnosis to HCT (P?=?0.0054) were risk factors after allogeneic HCT. Strategies that carefully select R/R MCL patients for autologous HCT may allow the identification of individuals suitable for allogeneic HCT.     

Hematopoietic cell transplantation for chronic myeloid leukemia in developing countries: perspectives from Latin America in the post-tyrosine kinase inhibitor era

Tyrosine kinase inhibitors (TKIs) are currently the first line treatment for chronic myelogenous leukemia (CML) in countries with high and intermediate-high gross national income. Hematopoietic cell transplantation (HCT) in these countries is considered salvage therapy for eligible patients who failed TKI or progress to advanced disease stages. In Latin America, treatment for CML also changed with availability of TKI in the region. However, many challenges remain, as the cost of this class of medication and recommended monitoring is high. CML treatment practices in Latin America demonstrate that the majority of patients are treated with TKI at some point after diagnosis, most commonly imatinib mesylate, but still TKI can only be used after interferon failure in some countries. Other treatment practices are different from established international guidelines, outlying the importance of continuing medical education. Allogeneic HCT is a treatment option for CML in this region and could be considered a cost-effective approach in a small subset of young patients with available donors, as the overall cost of long-term non-transplant treatment may surpass the cost of transplantation. However, there are many challenges with HCT in Latin America such as access to experienced transplant centers, donor availability, and cost of essential drugs used after transplant, which further impacts expansion of this treatment approach in patients in need. In conclusion, Latin American patients with CML have access to state of the art CML treatment. Yet, drug costs have a tremendous impact on developing health systems. Optimization of CML treatment in the region with appropriate monitoring, recognizing patients who would be transplant candidates, and expanding access to transplantation for eligible patients may curtail these costs and further improve patient care.     

Bone loss and avascular necrosis of bone after hematopoietic cell transplantation

Advances in transplantation technology and supportive care measures have resulted in significant decrease in early mortality resulting in continued growth in the number of long-term hematopoietic cell transplantation (HCT) survivors. The intensity of chemotherapy and total body irradiation regimen used pretransplantation to eradicate the primary disease can lead to organ toxicities, including significant bone complications after HCT. Bone loss is frequent in HCT recipients and results from impaired bone mineralization through disturbances of calcium and vitamin D homeostasis, osteoblast and osteoclast dysfunction, and deficiencies in growth or gonadal hormone secretion. Exposure to glucocorticoids and calcineurin inhibitors for prevention and treatment of graft-versus-host disease (GVHD) represents one of the major causes for the increased risk of osteoporosis and avascular necrosis of bone (AVN) in recipients of allogeneic HCT. In this article we review the incidence, pathogenesis, and risk factors for osteoporosis and AVN after allogeneic HCT and discuss general guidelines for their treatment and monitoring based on the limited available reports.     

Are reduced-intensity transplants safe in older patients with hematologic malignancies?

Non-myeloablative allogeneic hematopoietic cell transplantation (HCT) offers a potentially curative therapy for older patients with hematologic malignancies. However, the treatment modality is underutilized and, to date, there are only limited data on outcomes in people older than 60 years. This study describes the toxicities and outcomes of non-myeloablative allogeneic HCT, conditioned with low-dose total body irradiation with or without fludarabine, in patients aged 60-75 years enrolled in prospective multicenter clinical trials. Increasing age was not associated with adverse outcome. Relapse risk and comorbidity burden predicted survival; fit patients with low risk of disease relapse did well after transplant regardless of age. Despite demonstrating the feasibility of non-myeloablative allogeneic HCT in patients aged 60-75 years, the study raises important questions regarding how best to manage older patients with high-risk hematologic malignancies and how to optimize our approach to allogeneic HCT in this age group.     

Baseline comorbidities in patients with rheumatoid arthritis who have been prescribed biological therapy: A case control study

AimTo determine whether rheumatoid arthritis (RA) patients who have been prescribed biological agents exhibit a different comorbidity burden than RA patients who take disease-modifying antirheumatic drugs (DMARDs) alone, and to understand the association between comorbidity and other variables, as well as the association between comorbidity and multimorbidity.MethodsThis observational case–control study included 114 RA patients treated with biological agents and a control group comprising 163 sex- and age-matched RA patients treated with DMARDs only. Current and previous data regarding the patients’ disease activity, comorbidities, and treatments were collected. The data were analysed using bivariate and multivariate regression models.ResultsThe patients who were prescribed biological agents exhibited poorer disease control, received more DMARDs and steroids, and underwent more total joint arthroplasties compared with the patients in the control group. However, the risk factors for cardiovascular disease and the comorbidity frequency were similar between cases and controls. The most prevalent comorbidities were hypertension, obesity, and respiratory, thyroid, and upper gastrointestinal disorders. The incidence of cardiovascular disease was low, and only 29% of the patients exhibited multimorbidities. A bivariate association of age, late diagnosis, joint replacements and a high score on the health assessment questionnaire score (HAQ) with comorbidity was observed. There were also correlations between the Charlson index and age, joint reconstructive surgery, disease activity (DAS28), and HAQ score. However, when binary logarithmic regression models were applied, only patient age remained significantly associated with comorbidity and multimorbidity [hazard ratio, 1.08; 95% confidence interval, 1.05–1.12; p < 0.0005].ConclusionRA patients taking biological drugs have a comorbidity burden equivalent to those treated with DMARDs alone. Age is the main predictive factor of comorbidity in these patients.     

Lungentransplantation

Lung transplantation has been established as an appropriate ultimate treatment strategy in end-stage lung disease, when all conventional therapeutic options have been exhausted. A successful transplantation should result in an improved quality of life as well as an increase in life-expectancy for certain diseases (cystic fibrosis, pulmonary fibrosis and pulmonary hypertension). There is still a critical need regarding the number of available donor organs. Presently, one out of six patients dies on the waiting list. In order to identify suitable candidates for transplantation a number of criteria require consideration. These include the exact etiology of the pulmonary or cardiac disease, but also patient age, physical mobility, nutritional and muscular status as well as a comprehensive assessment to exclude significant extra-pulmonary co-morbidities. Complications arising after transplantation occur because of general perioperative risks, but also as a result of specific issues such as acute or chronic graft rejection, airway stenoses, infections of the newly immunosuppressed patient as well as a complete spectrum of secondary extra-pulmonary conditions. Comprehensive follow-up care in lung transplantation patients remains a vital issue. Analyses have shown a relevant improvement in long-term outcome, when follow-up care is delivered in cooperation with an established large volume transplant centre.     

Liver transplantation in the treatment of hepatocellular carcinoma

We aimed to determine the most appropriate candidates for liver transplantation based on their survival outcomes. Two hundred and fourteen patients who were transplanted in the presence of hepatocellular carcinoma (HCC) were analyzed. Patient groups were selected as “good risk” candidates for transplantation by our previously developed artificial network model or by the classic pTNM pathological classification system. The survival of the model-selected candidate groups was then compared to the survival of the candidates chosen as “good risk” by the pTNM classification (i.e., pTNM stages I + II and pTNM stages I + II + III). Suitability for transplantation was judged by long-term survival rates (i.e., 1—10 years post-transplant). By using the neural network prediction model and the subsequent subgroup case analysis, it was possible to generate those combinations of risk factors which predetermined patient survival through HCC recurrence. By applying the developed neural network model to the transplant candidate pool for patients with HCC, it was possible to select the maximum number of suitable candidates for transplantation while minimizing donor organ loss to recurrent HCC.     

Hematopoietic cell transplantation specific comorbidity index as an outcome predictor for patients with acute myeloid leukemia in first remission: combined FHCRC and MDACC experiences

A new hematopoietic cell transplantation-specific comorbidity index (HCT-CI) was effective in predicting outcomes among patients with hematologic malignancies who underwent HCT at Fred Hutchinson Cancer Research Center (FHCRC). Here, we compared the performance of the HCT-CI to 2 other indices and then tested its capacity to predict outcomes among 2 cohorts of patients diagnosed with a single disease entity, acute myeloid leukemia in first complete remission, who underwent transplantation at either FHCRC or M. D. Anderson Cancer Center (MDACC). FHCRC patients less frequently had unfavorable cytogenetics (15% versus 36%) and HCT-CI scores of 3 or more (21% versus 58%) compared with MDACC patients. We found that the HCT-CI had higher sensitivity and outcome predictability compared with the other indices among both cohorts. HCT-CI scores of 0, 1 to 2, and 3 or more predicted comparable nonrelapse mortality (NRM) among FHCRC and MDACC patients. In multivariate models, HCT-CI scores were associated with the highest hazard ratios (HRS) for NRM and survival among each cohort. The 2-year survival rates among FHCRC and MDACC patients were 71% versus 56%, respectively. After adjustment for risk factors, including HCT-CI scores, no difference in survival was detected (HR: 0.98, P = .94). The HCT-CI is a sensitive and informative tool for comparing trial results at different institutions. Inclusion of comorbidity data in HCT trials provides valuable, independent information.     

Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT

We previously reported that the Charlson Comorbidity Index (CCI) was useful for predicting outcomes in patients undergoing allogeneic hematopoietic cell transplantation (HCT). However, the sample size of patients with scores of 1 or more, captured by the CCI, did not exceed 35%. Further, some comorbidities were rarely found among patients who underwent HCT. Therefore, the current study was designed to (1) better define previously identified comorbidities using pretransplant laboratory data, (2) investigate additional HCT-related comorbidities, and (3) establish comorbidity scores that were suited for HCT. Data were collected from 1055 patients, and then randomly divided into training and validation sets. Weights were assigned to individual comorbidities according to their prognostic significance in Cox proportional hazard models. The new index was then validated. The new index proved to be more sensitive than the CCI since it captured 62% of patients with scores more than 0 compared with 12%, respectively. Further, the new index showed better survival prediction than the CCI (likelihood ratio of 23.7 versus 7.1 and c statistics of 0.661 versus 0.561, respectively, P < .001). In conclusion, the new simple index provided valid and reliable scoring of pretransplant comorbidities that predicted nonrelapse mortality and survival. This index will be useful for clinical trials and patient counseling before HCT.     

Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation

Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources (eg, umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, peri-, and posttransplant exposures and risk factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplantation experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This review provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.     

Pulmonary rehabilitation and COPD

Pulmonary rehabilitation has been well established and increasingly recommended in disease management plans for patients with chronic obstructive pulmonary disease. Key elements include a multidisciplinary approach to care, focus on the individual patient, and attention to emotional and social as well as physical aspects of health. Appropriate candidates are symptomatic patients with chronic lung disease who are aware of their disability and motivated to participate actively in their own health care. Pulmonary rehabilitation has also been useful for patients with other types of chronic lung diseases. Program components include a careful patient evaluation, education, instruction in respiratory and chest physiotherapy techniques, exercise training, and psychosocial support. Benefits demonstrated in a growing body of evidence include improvement in symptoms, exercise tolerance, and quality of life and reduction in utilization of health care resources. Pulmonary rehabilitation has also been included as an adjunct to surgical programs such as lung transplantation and lung volume reduction surgery.     

Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation

Advances in hematopoietic cell transplantation (HCT) technology and supportive care techniques have led to improvements in long-term survival after HCT. Emerging indications for transplantation, introduction of newer graft sources (for example, umbilical cord blood) and transplantation of older patients using less intense conditioning regimens have also contributed to an increase in the number of HCT survivors. These survivors are at risk for developing late complications secondary to pre-, peri- and post-transplant exposures and risk factors. Guidelines for screening and preventive practices for HCT survivors were published in 2006. An international group of transplant experts was convened in 2011 to review contemporary literature and update the recommendations while considering the changing practice of transplantation and international applicability of these guidelines. This report provides the updated recommendations for screening and preventive practices for pediatric and adult survivors of autologous and allogeneic HCT.     

Cardiovascular assessment in liver transplant for nonalcoholic steatohepatitis patients:What we do,what we should do

Non-alcoholic fatty liver disease(NAFLD) is increasing considerably due to the current lifestyle,which means that it is becoming one of the main indications for liver transplantation.On the other hand,there is a strong association between NAFLD and cardiovascular disease.This has been evidenced in many studies revealing a higher presence of carotid plaques or carotid intima-media thickness,leading to cardiovascular events and,ultimately,mortality.According to the liver transplant guidelines,screening for heart disease in transplant candidates should be performed by electrocardiogram and transthoracic echocardiography while a stress echocardiogram should be reserved for those with more than two cardiovascular risk factors or greater than 50 years old.However,there are no specific recommendations in NAFLD patients requiring a liver transplantation,despite its well-known cardiovascular risk association.Many studies have shown that these patients probably require a more exhaustive assessment and a global approach including other specialists such as cardiologists or nutritionists.Also,the incidence of cardiovascular disease is also increased in NAFLD patients in the post-transplantation period in comparison with other etiologies,because of the pre-existent risk factors together with the immunosuppressive therapy.Therefore,an early intervention on the lifestyle and the individualized selection of the immunosuppressive regimen could lead to a modification of the cardiovascular risk factors in NAFLD patients requiring a liver transplantation.