Autologous Recipients Research Articles

Pertussis Immunity and Response to Tetanus-Reduced Diphtheria-Reduced Pertussis Vaccine (Tdap) after Autologous Peripheral Blood Stem Cell Transplantation

Pertussis is a highly contagious respiratory infection characterized by prolonged cough and inspiratory whoop. Despite widespread vaccination of children aged<7 years, its incidence is steadily increasing in adolescents and adults, because of the known decrease in immunity following childhood immunization. In an effort to reduce pertussis in adolescents and adults, 2 vaccines containing tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) (BOOSTRIX and Adacel) were licensed in 2005 for use in adolescents, 1 of which (Adacel) contains less pertussis toxoid (PT) for use in adults. This study assessed pertussis titers in 57 adult survivors of an autologous peripheral blood stem cell transplantation (PBSCT; median age, 37.5 years), 28 of whom were subsequently vaccinated with Tdap containing 2.5microg of PT (Adacel). The median time to Tdap administration was 3 years posttransplantation. Before vaccination, 87% of the patients lacked pertussis immunity. Only 2 of the 28 patients developed a >2-fold response to PT following vaccination with Tdap. These data suggest that autologous transplantation recipients are highly susceptible to pertussis and that immunization with 2.5microg of PT induces an inadequate response. Prospective trials evaluating BOOSTRIX, containing 8microg/dose of PT (approved for adults in December 2008) are warranted in this vulnerable population undergoing transplantation.

Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplantation Recipients: A Global Perspective

In the past decade, modifications in HCT management and supportive care have resulted in changes in recommendations for the prevention of infection in HCT patients. These changes are fuelled by new antimicrobial agents, increased knowledge of immune reconstitution, and expanded conditioning regimens and patient populations eligible for HCT. Despite these advances, infection is reported as the primary cause of death in 8% of autologous HCT patients and 17 – 20% of allogeneic HCT recipients [3]. The major changes in this document, including changes in recommendation ratings, are summarized here. The organization of this document is similar to the previous guidelines. Specifically, the prevention of exposure and disease among pediatric and adult autologous and allogeneic HCT recipients is discussed. The current recommendations consider myeloablative and reduced intensity conditioning for allogeneic HCT similarly since data on infectious complications following reduced intensity conditioning compared to myeloablative conditioning are sparse [4–7]. However, increased information regarding post-transplant immune recovery highlighting differences between myeloablative and reduced intensity HCT are included. The sections of the document have been re-arranged in an attempt to follow the time course of potential infectious risks for patients receiving HCT. Following the background section, information on hematopoietic cell product safety is provided. The subsequent sections discuss prevention of infection by specific micro-organisms. Following organism-specific information, the sections then discuss means of preventing nosocomial infections as well as “do’s and don’ts” for patients following discharge post-transplant. Finally, information on vaccinations is provided. This will hopefully allow the reader to follow the prevention practices needed from the time a donor is selected until the patient regains immune competence. Several topics are new or expanded from the prior document (Table 2). These include information on multiple organisms which were previously not discussed but have seemingly become more clinically relevant in HCT patients over the past decade. Data, and where possible, recommendations are provided regarding the following organisms that were not included in the previous document: Bordetella pertussis; the polyomaviruses BK and JC; hepatitis A, B, and C viruses; human herpesviruses 6, 7, and 8; human metapneumovirus; human immunodeficiency virus; tuberculosis; nocardiosis; malaria; and leishmaniasis. In recognition of our global society, several organisms are discussed that may be limited to certain regions of the world. Included in that section are also those infections that may be ubiquitous but occur infrequently, such as Pneumocystis jiroveci and Nocardia. Table 2 Summary of Changes compared to the Guidelines published in 2000 [1]. Several other changes should be noted. For bacterial infections, these guidelines now recommend quinolone prophylaxis for patients wth neutropenia expected to last as least 7 days (BI). Additionally, the recommendations for contact precautions (AIII), vaccination (BI), and prophylaxis patients with GVHD (AIII) against Streptococcus pneumoniae have been strengthened. The subsection on central line associated blood stream infections is now in the bacterial section. The vaccination section has been dramatically expanded. Changes include the recommendations for PCV rather than PPSV-23 for pneumococcal vaccination, starting some vaccinations earlier post-transplant, and the addition of recommendations for Varivax, HPV vaccine, and (the non-use of) Zostavax vaccine are included. Two additional appendices were added to provide information on desensitization to sulfa drugs and visitor screening questionnaires. Finally, the dosing appendix has merged both adult and pediatric dosing and provides recommendations for several newer antimicrobial agents that were not previously available. In summary, the changes and expansion to this document reflect the growing body of literature detailing infectious complications in HCT patients.

Safety and tolerability of the antimicrobial peptide human lactoferrin 1-11 (hLF1-11)

BackgroundThe treatment of patients with haematological malignancies by means of haematopoietic stem cell transplantation (HSCT) is often accompanied by life threatening infections. With emerging antimicrobial resistance there is an increased need for new agents, with a beneficial safety profile. Therefore we evaluated the safety of the promising new antimicrobial peptide human lactoferrrin 1-11 (hLF1-11) in healthy volunteers and patients.MethodsWe undertook a sequential, randomised, double-blind, placebo-controlled study using ascending single (0.005, 0.05, 0.5, 5 mg) and multiple intravenous doses (0.5, 5 mg) in healthy volunteers, and open-label, single intravenous 5 mg doses in autologous HSCT recipients.ResultsSingle and multiple doses of hLF1-11 were tolerable up to 5 mg intravenously in healthy volunteers, while 5 mg single dose was tolerable in patients. Elevations in transaminases possibly related to treatment were reversible and not serious.ConclusionThe new antimicrobial hLF1-11 is well tolerated in healthy volunteers with repeated daily doses up to 5 mg. The side-effect profile is very favourable for an antimicrobial, the only undesirable effect being a possible elevation of transaminases, which may be related to hLF1-11 although the current data do not allow conclusive interpretation of treatment relationship. A lower dose is recommended for the forthcoming multiple dosing studies in HSCT patients.Trial registrationClinicalTrials.gov: nct00509938.

High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia

A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients' characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3-16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation.

Impaired Proinsulin Processing is a Characteristic of Transplanted Islets

We sought to determine whether recipients of islet transplants have defective proinsulin processing. Individuals who had islet allo- or autotransplantation were compared to healthy nondiabetic subjects. Insulin (I), total proinsulin (TP), intact proinsulin and C-peptide (CP) were measured in samples of fasting serum by immunoassay, and the ratios of TP/TP+I and TP/CP were calculated. Islet allotransplant recipients had elevated TP levels relative to nondiabetic controls (16.8 [5.5-28.8] vs. 8.4 [4.0-21.8] pmol/L; p < 0.05) and autologous transplant recipients (7.3 [0.3-82.3] pmol/L; p < 0.05). Islet autotransplant recipients had significantly higher TP/TP+I ratios relative to nondiabetic controls (35.9 +/- 6.4 vs. 13.9 +/- 1.4%; p < 0.001). Islet allotransplant recipients, some of whom were on insulin, tended to have higher TP/TP+I ratios. The TP/CP ratio was significantly higher in both islet autotransplant (8.9 [0.6-105.2]; p < 0.05) and allotransplant recipients (2.4 [0.8-8.8]; p < 0.001) relative to nondiabetic controls (1.4 [0.5-2.6]%). Consistent with these findings, TP/TP+I and TP/CP values in islet autotransplant recipients increased significantly by 1-year posttransplant compared to preoperative levels (TP/CP: 3.8 +/- 0.6 vs. 23.3 +/- 7.9%; p < 0.05). Both allo- and autotransplant subjects who received <10,000 IE/kg had higher TP/CP ratios than those who received >10,000 IE/kg. Islet transplant recipients exhibit defects in the processing of proinsulin similar to that observed in subjects with type 2 diabetes manifest as higher levels of total proinsulin and increased TP/TP+I and TP/CP ratios.

3007 Herpes zoster in solid tumor and hematologic malignancy patients – a cohort study in a managed care organization

The epidemiology of herpes zoster (HZ) in contemporary autologous hematopoietic cell transplant (HCT) recipients, and the impact of acyclovir (ACV)/valacyclovir (VACV) prophylaxis, is not well described. In this observational study from 2002 to 2010, we retrospectively identified 1000 varicella zoster virus (VZV)–seropositive autologous HCT recipients with up to 5 years of follow-up. The incidence of HZ and use of ACV/VACV prophylaxis were determined through review of medical records and mailed questionnaires. Risk factors for HZ were determined by multivariable Cox regression. Over a period of 5 years after autologous HCT, 194 patients developed at least 1 HZ episode, with a cumulative incidence of 21%; 159 of 194 (82%) were not on prophylaxis at the time of HZ. A second episode of HZ occurred in 31 of 194 (16%) patients. Patients taking ACV/VACV had reduced risk for HZ (adjusted hazard ratio [aHR], .59; 95% confidence interval [CI], .37 to .91), whereas those older than the median age (≥55.5 years) had increased risk (aHR, 1.42; 95% CI, 1.05 to 1.9). Disseminated VZV was reported in 8% and postherpetic neuralgia in 13% of patients. We demonstrate a high burden of HZ late after autologous HCT, despite long-term antiviral prophylaxis. Improved prevention strategies are needed to provide sustained protection against HZ after autologous HCT.

Diffuse alveolar hemorrhage after unrelated cord blood transplantation

Diffuse alveolar hemorrhage (DAH) is a recognized pulmonary complication in the setting of hematopoietic STC (HSCT). DAH after HSCT is often fatal, but the exact etiology remains unclear. DAH after HSCT is reported in 1–5% of autologous graft recipients and in 3–7% of allogeneic graft recipients.1, 2, 3, 4 Umbilical cord blood transplantation (CBT) from unrelated donors has recently increased in popularity for adult patients with hematological diseases who have no other suitable donor. However, DAH in the setting of post CBT has not been discussed in detail.4 We describe herein, a case of a patient with DAH after CBT who was successfully treated with relatively low-dose steroid therapy using prednisolone at 1 mg/kg/day.

Osteochondroma after Hematopoietic Stem Cell Transplantation in Childhood. An Italian Study on Behalf of the AIEOP-HSCT Group

A retrospective study was conducted among Italian children treated with hematopoietic stem cell transplant (HSCT) to evaluate the incidence and risk factors in the development of osteochondroma (OC). OC occurred in 27 patients who received autologous or allogeneic HSCT. The estimated 5-, 10-, and 15-year cumulative risk of developing OC was 0.5%, 3.2%, and 6.1%, respectively. Analysis of cumulative risk stratified by the various risk factors revealed that male sex (P=.026), autologous HSCT (P=.001), age at HSCT (< or =3 years) (P < .0001), and total body irradiation (TBI) (P <.0001) significantly affected the risk of OC. Multivariate analysis, restricted only to tumor types with at least 1 case of OC, showed that earlier age at HSCT (P =.0004) and TBI (P < .0001) were the only factors that were significantly associated with OC.

Relative Survival of Long-Term Hematopoietic Cell Transplant Recipients Approaches General Population Rates

Whether the annual mortality rates of long-term hematopoietic cell transplant (HCT) survivors ever return to that of the general population is unclear. This study sought to determine the annual long-term mortality rates of allogeneic and autologous HCT recipients who had survived 5 years or more disease-free posttransplant and calculate their relative survival rates. Patients were included if they had a first allogeneic or syngeneic HCT for acute leukemia, chronic myelogenous leukemia (CML) or myelodysplastic syndromes (MDS), or autologous HCT for acute myelogenous leukemia (AML) or lymphoma in Australia or New Zealand between 1992 and 2001, recorded on the Australasian Bone Marrow Transplant Recipient Registry (ABMTRR) database, and were known to have survived, disease free, 5 years or more posttransplant. The annual mortality rates of 5-year transplant survivors were compared to standard Australian and New Zealand populations using relative survival. A total of 1461 HCT survivors (688 postallograft, 773 postautograft) were included in this study. The 10-year survival probability for 5-year allograft survivors was slightly higher than that of 5-year autologous survivors (93.4% versus 89.6%, P=.06). The relative survival of both allogeneic and autologous 5-year survivors was never <97% of that of the general population. However, it was statistically significantly lower than expected in the sixth to ninth years posttransplant, with no obvious pattern of either improvement or deterioration from 6 to 10 years posttransplant. This study indicates that annual relative survival rates of long-term survivors of allogeneic HCT performed in Australia and New Zealand for acute lymophoblastic leukemkia (ALL), AML, CML, and MDS are slightly, but significantly lower than population rates in the 6th to 10th years posttransplant. Annual relative survival rates of long-term survivors of autologous HCT performed in Australia and New Zealand for AML and lymphomas are also slightly lower than population rates up to the 10th year posttransplant. Late deaths from transplant and disease-related causes are unusual, but continue to occur for many years post-HCT.

Efficacy of palifermin (keratinocyte growth factor-1) in the amelioration of oral mucositis

Oral mucositis is a significant toxicity of cytotoxic chemo- and radiation-therapy used to treat cancer. Palifermin is the first pharmaceutical/biological agent approved for the intervention of oral mucositis. The major objective of this review is to evaluate the evidence supporting the use of palifermin. A literature search was performed using an appropriate keyword search in MEDLINE and PubMed databases. Of 100 full papers and 4 abstracts identified, 12 papers and 3 abstracts were appropriate for analysis. Level 2 evidence supporting palifermin use in patients with hematologic malignancies being treated with autologous hematopoietic stem cell transplantation (HSCT) is clear. Level 2 evidence also exists for the use of palifermin in the prevention of oral mucositis in patients with solid tumors (colorectal cancer, head and neck cancer), but is incomplete. Level >/= 3 data support the use of palifermin in allogeneic HSCT recipients and cycled chemotherapy. A single health economic study concluded that palifermin is essentially cost neutral in the autologous HSCT population. Data supporting the use of palifermin in autologous HSCT recipients with hematologic malignancies is clear. Some data exist demonstrating its efficacy in other oncologic indications. Additional studies are needed to broaden the potential applications of palifermin and to ascertain its economic, but not symptomatic, effectiveness.

Predictors of avascular necrosis of bone in long‐term survivors of hematopoietic cell transplantation

Avascular necrosis (AVN) is a debilitating condition reported after chronic steroid use. The purpose of this study was to describe the magnitude of risk in individuals who survived >or=1 years after hematopoietic cell transplantation (HCT), and to investigate the role of immunosuppressive agents such as prednisone, tacrolimus (FK506), mycophenolate mofetil (MMF), and cyclosporine (CSA) in the development of AVN after HCT. Using a retrospective study design, the authors followed 1346 eligible patients for the development of AVN. Cumulative incidence was calculated taking into consideration competing risk from death and disease recurrence. Cox proportional regression techniques were used to identify associated risk factors. The median age at HCT was 34 years (range, 7 months-69 years), and median length of follow-up for those surviving was 8.2 years. Seventy-five patients developed AVN of 160 joints. The cumulative incidence of AVN at 10 years was 2.9% after autologous HCT, 5.4% after allogeneic matched related donor HCT, and 15% after unrelated donor HCT (P<.001 compared with autologous HCT recipients). For allogeneic transplant recipients, male sex (relative risk [RR], 2.1; 95% confidence interval [95% CI], 1.1-4.0); presence of chronic graft-versus-host disease (RR, 2.2); and exposure to CSA, FK506, prednisone, and MMF rendered patients at increased risk, especially in patients with a history of exposure to >or=3 drugs (RR, 9.2; 95% CI, 2.42-35.24). Future studies examining the pathogenetic mechanism underlying AVN should help develop targeted interventions to prevent this chronic debilitating condition.

Incidence and Risk of Postherpetic Neuralgia after Varicella Zoster Virus Infection in Hematopoietic Cell Transplantation Recipients: Hokkaido Hematology Study Group

To assess the incidence of and risk factors associated with postherpetic neuralgia (PHN) after hematopoietic cell transplantation (HCT) varicella zoster virus (VZV) infection, we conducted a retrospective chart review of 418 consecutive patients who underwent HCT between April 2005 and March 2007. The male/female ratio was 221/197, median age at HCT was 47 years (range: 0-69 years), and autologous/allogeneic/syngeneic HCT ratio was 154/263/1. Seventy-eight patients developed VZV infection after HCT. Sixty-two patients had localized zoster, 11 patients had disseminated zoster (rash like chicken pox), and 4 patients had visceral zoster. All cases were treated with acyclovir (ACV) or valacyclovir (VACV), and there was no VZV infection-related death. Twenty-seven (35%) of the 78 patients with VZV infection suffered PHN after resolution of VZV infection. Multivariate analysis showed that advanced age is the only risk factor in autologous HCT (P = .0075; odds ratio [OR] = 1.14; 95% confidence interval [CI], 0.97-1.33). On the other hand, advanced age (P = .0097; OR = 1.06; 95% CI, 1.01-1.12), male gender (P = .0055; OR = 12.7; 95% CI, 1.61-100.1), and graft-versus-host disease (GVHD) prophylaxis with a tacrolimus-based regimen (P = .0092; OR = 9.56; 95% CI, 1.44-63.3) were associated with increased risk of PHN in allogeneic HCT. This study for the first time clarified the risk of PHN in HCT recipients.

Revaccination of bone marrow transplant recipients: a review of current practices in Australia

Vaccination following bone marrow transplant (BMT) is an important part of ongoing care and disease prevention. The aim of the study was to investigate vaccination procedures in BMT recipients and identify what systems are in place throughout Australia to remind and alert patients concerning their need for vaccination. Questionnaires were sent to haematologists managing BMT recipients in Australia to examine post-BMT vaccination practices in hospitals and outpatient clinics. Questionnaires were also sent to BMT recipients in New South Wales, who had their transplants (either allogeneic or autologous) in the past 5 years to determine what vaccinations they had received and what vaccination reminder systems had been used. Vaccine recommendations and practices by BMT physicians showed little consensus. They also differed greatly between autologous and allogeneic transplant recipients. Only just more than half of the physicians had an effective reminder system in place and only 12 of 34 patients had received vaccination reminders. One-third of all patients were not aware of any need for revaccination. The disparity in physician practice regarding revaccination is significant and may reflect the lack of data available regarding efficacy of revaccination in this setting and/or a lack of knowledge about recommendations. Because of this, a national immunization schedule for post-BMT patients founded on evidence-based studies is required to provide optimal patient care. The lack of effective follow up and reminder systems ensuring patient completion of vaccination schedules is also an area needing improvement.

Prediction of acute volume loss in spontaneously breathing subjects

Studies of critically ill hematopoietic stem cell transplantation (HSCT) recipients have mainly been single-center and focused on allogenic HSCT recipients. We aimed to describe a cohort of autologous HSCT with an unplanned intensive care unit (ICU) admission.This study is a retrospective cohort study of autologous HSCT performed as a treatment for a hematological malignancy, during their first unplanned ICU admission in 50 hospitals in Brazil. We assessed the hospital mortality and the association between mechanical ventilation, vasopressors, and renal replacement therapy and hospital mortality in autologous HSCT recipients, adjusted for potential confounders.We included 301 patients. Multiple myeloma was the most common malignancy driving to HSCT. ICU and hospital mortality were 22.9% and 37.5%, respectively. After adjustment for potential confounders, mechanical ventilation (OR = 9.10; CI 95%, 4.82–17.15) was associated with hospital mortality, but vasopressors (OR = 1.43; CI 95%, 0.77–2.64) and renal replacement therapy (OR = 1.30; CI 95%, 0.63–2.66) were not.In this large cohort of critically ill autologous HSCT recipients, mechanical ventilation was the only organ support-therapy associated with increased mortality in autologous HSCT recipients.

A Customized Patient Donor Information (PDI) Application for Pre-Hematopoietic Stem Cell Transplantation (HSCT) Data Collection And Deviation to Standard Of Care Tracking Tool

All prospective autologous and allogeneic progenitor cell recipients and allogeneic donors must undergo pre-HSCT evaluation. Collection of defined elements of the evaluation process in real time with frequent updates requiring daily communication between physicians and HSCT staff is challenging, especially in a large HSCT program. Efficient data collection and management of pre-HSCT evaluation data allows inpatient and outpatient personnel the ease of accessing useful information on a patient in a quick and efficient manner, and should result in high quality of data for patient registration to CIBMTR.

Severe sepsis in autologous stem cell transplant recipients: Microbiological aetiology, risk factors and outcome

Infectious complications are the main reason for early treatment-related mortality after autologous stem cell transplantation (ASCT). We evaluated retrospectively microbiological aetiology, risk factors and clinical consequences of severe sepsis in this patient cohort. From 1996 to 2006 a total of 319 patients underwent ASCT at our institution. Antibacterial prophylaxis was not used. Neutropenic fever occurred in 83% (n=265) and was complicated by severe sepsis in 5% (n=17) of patients. Severe sepsis tended to be more common in patients with non-Hodgkin's lymphoma (NHL) than in other patients (9% vs 3%, p=0.009). Bacteraemia was observed more commonly in patients with severe sepsis (76% vs 22%, p<0.001); Pseudomonas sp. was found in 30% (n=5) of these patients. Kinetics of C-reactive protein (CRP) more commonly coincided with, rather than predicted, the development of severe sepsis. All other observed risk factors for severe sepsis (length of neutropenia, fever and blood culture findings) were late indicators. Severe sepsis was fatal in 9 patients (53%), and all had NHL (p=0.003 compared to other patients). Severe sepsis is an important cause of early mortality after ASCT, especially in NHL patients. Ways to prevent development of severe sepsis or predict its development might reduce early mortality among ASCT recipients.

Late Effects after Autologous Hematopoietic Cell Transplantation

Over 30,000 autologous hematopoietic cell transplants (HCT) have been performed yearly during the past decade. With improvement in supportive care, few patients succumb to early treatment complications; hence, more attention is being paid to causes of late complications and death. However, interpretation of the data that exist is difficult as the definition of ‘‘late’’ varies by study, as does the patient population, underlying diseases, HCT mobilization and conditioning regimens, stem cell sources, and duration of follow-up (Table 1). Most importantly, the methods used to estimate the incidence of late complications over time are different or are not explained in sufficient detail. Some studies report relative risk or standardized mortality compared with the general population. Other studies report an acturial estimate (which ignores competing risks and thus may overestimate the incidence), whereas others report cumulative incidence calculations.

Low MHC-I density impairs the homeostatic proliferation of CD8 T cells after HSCT

We hypothesise that the modifications in the Major Histocompatibility Class I (MHC-I) expression after Hematopoietic Stem Cell Transplantation (HSCT) might impact on CD8 T cell recovery. To evaluate our proposal, we measured the number of peripheral CD8 T cells and the MHC-I expression on the monocytes from the patients who underwent allogenic or autologous HSCT. Three months after transplantation, almost all of the autologous recipients showed a high density of MHC-I and the CD8 T cell counts were within the normal range. In contrast, allogeneic recipients had low or heterogeneous expression of MHC-I and low numbers of CD8 T cells. Similar patterns were observed even after 6 to 20 months after transplantation. Recent thymic emigrants and serum levels of IL-7 and IL-15 were similar within both groups of patients. Together, our results indicate that Homeostatic Peripheral Expansion (HPE) is the main mechanism to reach the normal numbers of CD8 T cells immediately after HSCT. A high and homogenous expression of MHC-I molecules is required for an optimal HPE.

Adaptation of family caregivers during the acute phase of adult BMT

This study examined the course of adaptation as indicated by the level of emotional distress for family caregivers of adult BM recipients across the acute phase of the transplant trajectory. Factors influencing caregivers' adaptation that could be potential markers of vulnerability to psychological and social morbidity were identified. The sample included 192 caregivers of either an autologous or allogeneic BMT recipient. Data were collected by self-report questionnaires at three time points in the trajectory: pre-transplant/pre-hospitalization (T1); during hospitalization, post-infusion (T2); 1 month post-discharge (T3). There was a decline in emotional distress from T1 to T3, and bivariate correlations indicated significant association of distress with variables hypothesized to be theoretically relevant. Specifically, greater personal control, a greater sense of spiritual connectedness, less disruption in the life of the caregiver and less use of avoidance coping were the strongest factors associated with lower emotional distress. In conclusion (1) levels of personal control and spirituality remained stable across time and were negatively associated with emotional distress. Therefore, they may provide an indication of caregiver resilience pre-transplant; (2) level of recipient symptomatology rather than BMT type appears to influence caregiver distress; (3) there are indications of the need for post-hospitalization follow-up with caregivers by the BMT team.

Delayed Cytomegalovirus (cmv) Infection Following Hematopoietic Cell Transplantation (HCT): City of Hope (COH) Experience.

Patients undergoing HCT are at an increased risk of developing primary and/or reactivated CMV infection, although the magnitude of risk of CMV disease has decreased with the widespread use of preemptive ganciclovir. Most episodes of reactivation occur within the first year post-HCT and are associated with risk factors such as CMV serostatus of donor and recipient, development of acute graft vs. host disease (GVHD): and the immunosuppressive therapy used for its management. Because of prolonged periods of immunosuppression post-HCT, patients may be at risk for delayed CMV infection one or more years after HCT. However, the magnitude of risk of delayed CMV infection and characteristics of those at increased risk has not been described. Given the high morbidity and mortality associated with post-HCT CMV infection, identifying patients at high risk of delayed CMV could be useful for effective management. This report includes 2700 consecutive patients who survived more than one year after undergoing HCT at COH between 1976 and 2003; these included 1404 autologous HCT recipients and 1296 allogeneic HCT recipients (1043 related donor; 253 unrelated donor recipients). Median age at HCT was 38 years (range, 0.6 to 79 years) and 59% of the cohort was males. Median follow-up time from HCT until delayed CMV infection/disease, death, or end of study period (12/31/2006), whichever occurred first, was 4.3 years (range:1–26.6 years). Medical records from COH and/or outside facilities were the main source of data for CMV occurrences. In total, 33 patients (1%) developed delayed CMV infection after surviving at least one year post-HCT (1 autologous and 32 allogeneic [20 related donor and 12 unrelated donor HCT]) developed a total of 40 episodes of delayed CMV that included pneumonia (n=16), gastrointestinal disease (n=8), retinitis (n=2), hepatitis (n=1), concurrent pneumonia and hepatitis (n=1), and asymptomatic reactivation (n=12). The overall cumulative incidence of delayed CMV infection was 1.3% (95% Confidence Interval [CI], 0.9–1.8%) at 5 years from HCT. For autologous HCT recipients, the incidence was 0.07% at 1 year based on 1 event. Among allogeneic HCT recipients, the cumulative incidence at 5 years post-HCT was 2.1% [95%CI, 1.2–3.0%] for related donor HCT recipients; and 5.0% [95%CI, 2.2–7.7%] for unrelated donor HCT recipients. Among allogeneic HCT recipients, the risk factors for the development of delayed CMV infection included unrelated donor HCT (hazard ratio [HR] = 2.5, 95% CI, 1.1–5.7) and CMV seropositive status of the recipient (HR=7.7, 95% CI 1.0–57.0) (Figure). Interestingly, donor CMV status was not associated with increased risk of delayed CMV. All 32 allogeneic HCT recipients experienced chronic GVHD, with prolonged exposures to corticosteroids (median=494 days), and cyclosporine (median=380 days). Thirty patients with delayed CMV infection (94% of the allogeneic HCT recipients with delayed CMV) were receiving immunosuppressive therapy for management of chronic GVHD at onset of delayed CMV. A total of eight patients with delayed CMV did not have a history of CMV infection in the first year, and were characterized by the following clinical and demographic features: 6 (75%) were male; median age at HCT was 35 years; one was an autologous HCT recipient, who relapsed 10 months post-HCT for non-Hodgkin lymphoma, received further chemotherapy and radiation, including Rituximab and then developed late CMV, just over one year post-HCT. The seven allogeneic HCT recipients had chronic GVHD, and were CMV serostatus positive prior to HCT, with 4 also having CMV seropositive donors. Of the 33 patients with delayed CMV in this study, 26 expired; median survival after the development of delayed CMV was 46 days. This study describes the magnitude of risk of delayed CMV infection in autologous and allogeneic HCT recipients and identifies at risk patients as those who are seropositive for CMV, undergoing unrelated HCT, and those with prolonged exposures to immunosuppressive therapy for cGVHD (Figure), suggesting the need for a close surveillance of these patients at high risk. [Display omitted]