A case of syngeneic graft-versus-host disease.

Graft-versus-host disease has been reported to occur rarely in syngeneic hematopoietic stem cell transplant recipients. Clinical and histological changes consistent with graft-versus-host disease have been reported to occur in this patient population. We report a case of a 46-year-old Caucasian male with diffuse large B-cell lymphoma in complete remission who underwent a syngeneic hematopoietic stem cell transplant. He was diagnosed with grade III acute skin and gastrointestinal graft-versus-host disease requiring high-dose corticosteroids and immunosuppressive therapy and resulting in a complete response. Syngeneic graft-versus-host disease is an anomaly that needs to be considered as a differential diagnosis of patients experiencing dermatitis, gastroenteritis, or hepatitis after an identical twin hematopoietic stem cell transplant.

Combining FDG-PET/CT with laboratory data yields superior results for prediction of relapse in multiple myeloma.

OBJECTIVES: The precise role of positron emission tomography (PET/CT) for predicting relapse/progression in multiple myeloma remains uncertain. We compared the predictive values of PET/CT, concurrent laboratory testing (labs), and their combination in prediction of 12-month progression, as determined by current International Myeloma Working Group (IMWG) criteria. METHODS: PET/CT and labs (serum chemistry, ß2-microglobulin, immunofixation, bone marrow biopsy, serum free light chains) were reviewed, and date of relapse/progression was determined by IMWG criteria. RESULTS: The median time from therapy to PET/CT imaging was 12.0 months (1.0-110) and median time to progression (TTP) was 29.8 months (1.6-130+). Overall survival and survival-without-progression at last follow-up were 84% and 49%, respectively. Sensitivity of PET/CT for predicting relapse/progression was lower than that of labs (0.67 vs. 0.89, ns), but PET/CT was more specific (0.89 vs. 0.79, ns). When labs and PET/CT data were combined, a positive result for either test was 89% sensitive and a positive result for both tests was 100% specific for predicting 12-month progression of disease. Kaplan-Meier analysis showed significantly greater TTP for those with a negative vs. positive PET/CT (P = 0.0005), negative vs. positive labs (P < 0.0001), and both tests negative vs. both tests positive (P < 0.0001). CONCLUSIONS: Combining PET/CT with laboratory data improves the accuracy of prediction of relapse/progression within 12 months compared with each test alone. Thus, integration of PET/CT into myeloma follow-up is recommended, and the impact of this approach on management should be explored.

Long-term Outcomes of team-based learning.

BACKGROUND: Team-based learning (TBL) is associated with improved end-of-course exam performance, but the impact on long-term retention is unknown. We compared the impact of three teaching methods: traditional case-based small group discussion (TSG), TBL or no small group reinforcement on short-term understanding and long-term retention after a haematology course. METHODS: Knowledge assessments were conducted prior to, immediately after and 14 months after course completion. Several topics covered by TSG were switched to TBL and could be directly compared. RESULTS: We recruited 24% of eligible students (n = 70). Of these, 48 completed the final assessment (69% retention). Pre-course, participants scored 31% correctly, which increased to 78% post-course with significant differences: TBL 87%; TSG 78%; no small group 76% (p < 0.01 for both comparisons). At long-term follow-up, the effect of the teaching method was no longer significant: TBL 75%; TSG 67% (p = 0.14); no small group 70% (p = 0.36). When restricted to topics converted from TSG to TBL, the long-term benefit was not shown: TSG 59%; TBL 54% (p = 0.47). FINDINGS AND DISCUSSION: We confirm increased understanding gained by using TBL, but this did not lead to better long-term retention. Improved scores on short-term testing has value for student well-being and competitiveness for residency application. TBL may still be of long-term benefit through modelling team decision making and self-directed learning that are core features of how clinical medicine is practiced. However, our findings argue against justifying the adoption of TBL on the basis of superior long-term retention.

It Takes a Team to Make It Through: The Role of Social Support for Survival and Self-Care After Allogeneic Hematopoietic Stem Cell Transplant.

BACKGROUND: Social support plays an important role for health outcomes. Support for those living with chronic conditions may be particularly important for their health, and even for their survival. The role of support for the survival of cancer patients after receiving an allogeneic hematopoietic cell transplant (alloHCT) is understudied. To better understand the link between survival and support, as well as different sources and functions of support, we conducted two studies in alloHCT patients. First, we examined whether social support is related to survival (Study 1). Second, we examined who provides which support and which specific support-related functions and tasks are fulfilled by lay caregivers and healthcare professionals (Study 2). METHODS: In Study 1, we conducted a retrospective chart review of alloHCT patients (N = 173, 42.8% female, age: M = 49.88) and registered availability of a dedicated lay caregiver and survival. In Study 2, we prospectively followed patients after alloHCT (N = 28, 46.4% female, age: M = 53.97, 46.4% ethnic minority) from the same hospital, partly overlapping from Study 1, who shared their experiences of support from lay caregivers and healthcare providers in semi-structured in-depth interviews 3 to 6 months after their first hospital discharge. RESULTS: Patients with a dedicated caregiver had a higher probability of surviving to 100 days (86.7%) than patients without a caregiver (69.6%), OR = 2.84, p = 0.042. Study 2 demonstrated the importance of post-transplant support due to patients' emotional needs and complex self-care regimen. The role of lay caregivers extended to many areas of patients' daily lives, including support for attending doctor's appointments, managing medications and financial tasks, physical distancing, and maintaining strict dietary requirements. Healthcare providers mainly fulfilled medical needs and provided informational support, while lay caregivers were the main source of emotional and practical support. CONCLUSION: The findings highlight the importance of studying support from lay caregivers as well as healthcare providers, to better understand how they work together to support patients' adherence to recommended self-care and survival.

Non-myeloablative conditioning and allogeneic transplantation for multiple myeloma.

In multiple myeloma (MM), allogeneic stem cell transplantation (alloHCT) carries a lower relapse risk than autologous transplantation but a greater transplant-related mortality. Nonmyeloablative conditioning for allogeneic transplantation (NST) reduces transplant-related toxicity. Results are encouraging when used during first remission in low-risk patients, but less-so in relapsed or refractory disease. This is a single-center retrospective analysis of 20 previously treated MM patients who underwent NST from matched-related or matched-unrelated donors from 2000-2006. Median age was 52.7 years (37.2-68.0). Twenty-five percent had advanced or high-risk disease. Eleven still had active disease prior to NST. Conditioning was total body irradiation 200 cGy on a single fraction on day -5, followed by antithymocyte globulin (ATG) 1.5 mg/kg/day and fludarabine 30 mg/m(2)/day on days -4 to -2. All received immunosuppression, most commonly with oral mycofenylate mofetil and cyclosporine beginning on day -5. At day 100, 50% had achieved complete remission. Transplant-related mortality was 25%. Median overall survival (OS) was 21.2 months (0.6-90+) and progression-free survival (PFS) 6.6 months (0.6-90+). Both OS and PFS were 24% at 3 years. OS was significantly greater for patients with age <52 years (median 27 months vs. 7.9 months, P = 0.031), and there was a trend toward greater OS for those with beta2 microglobulin <2.5 mg/l (median 27 months vs. 7.7 months, P = 0.08). Donor characteristics and Ig type had no significant effect on survival. These data suggest a benefit of NST in relapsed/refractory MM. Randomized trials must be performed to confirm and further qualify this benefit.

Hemolysis and Hemoglobin Structure and Function: A Team-Based Learning Exercise for a Medical School Hematology Course.

Introduction: This team-based learning (TBL) exercise focused on hemolysis and hemoglobin structure and function. The goal was to emphasize content that directly impacts clinical practice, but obliges students to understand underlying pathophysiology. The readiness assurance test (RAT) covers oxygen affinity, diagnosing hemolysis, inherited causes of hemolysis (G6PD deficiency, hereditary spherocytosis, sickle cell disease, thalassemia) and acquired causes of hemolysis (thrombotic microangiopathies, autoimmune hemolytic anemia). The application activity focused on thalassemia, sickle cell disease, and autoimmune hemolytic anemia. Methods: Second-year students were divided into teams of five to six students each with one facilitator for each classroom. Students completed an individual RAT (iRAT) followed by a group RAT (gRAT). The facilitator reviewed answers of the RATs emphasizing questions where there was a lack of clarity about the correct answer. Students completed the application activity within their teams followed by a discussion guided by the facilitator. Results: On average, students answered 63% of answers correctly on the iRAT. The average team score on the gRAT was 26.7 out of 30 points. The session was well reviewed by both students and facilitators. Students ranked the quality of all facilitators as excellent with an average rating of 4.4 of 5. Exam scores improved compared to prior to the introduction of TBL, but this was also found for material not covered. Discussion: The use of TBL to emphasize the relationship between pathophysiology and the diagnosis and management of patients was both an effective teaching method and a successful way to engage medical students.

Prevalence of Cytopenia in the General Population-A National Health and Nutrition Examination Survey Analysis.

BACKGROUND: Cytopenia, a reduced count of blood cells manifesting as anemia, neutropenia, and/or thrombocytopenia is frequently associated with other medical conditions. However, a cytopenia may not be accompanied by a known determinant and in some of these cases, may be a precursor to pre-malignancies or hematologic cancers. Little is known about the prevalence of these unexplained cytopenias and their distribution in the population. MATERIALS AND METHODS: The National Health and Nutrition Examination Survey (NHANES) from 1999 to 2002 was used to identify those with a cytopenia in the general population. Those without an identifiable determinant in the NHANES were classified as having unexplained cytopenia. Weighted frequencies were examined to assess the prevalence of unexplained cytopenia in the population. Distribution of blood counts comparing those with unexplained cytopenia to the general population was examined. Multivariable logistic regression was conducted to assess the association between unexplained cytopenia and demographic factors. RESULTS: Of the 7,962 people in the sample, 236 (2.0%) had any cytopenia and 86 (0.9%) had an unexplained cytopenia. Approximately 43% of all cytopenias were not accompanied by a clinical determinant. Unexplained cytopenia was more common in men (1.1%) than in women (0.7%) and in Non-Hispanic Black participants (3.4%). Among those with an unexplained cytopenia, the majority (74.8%) manifested as neutropenia. Compared to those with no cytopenia, those with unexplained cytopenia were significantly less likely to be female, have body mass index ≥30 kg/m2, and work in the service industry, and were significantly more likely to be non-Hispanic Black. CONCLUSIONS: This is the first study to examine the prevalence of unexplained cytopenia in a nationally representative sample and may serve as a baseline for comparison with other populations. Future research to identify risk factors for development of malignant hematological disorders among those with unexplained cytopenia is warranted.

Combined bone marrow and peripheral blood progenitor cell autografts for patients with poor mobilization.

BACKGROUND AIMS: Peripheral blood progenitor cell (PBPC) autografts with low CD34(+) cell content provide inadequate platelet (Plt) and red blood cell (RBC) reconstitution. Repeat collection and bone marrow (BM) harvesting are used in this situation. Minimum cell contents for BM-PBPC combined grafts are undefined. METHODS: A retrospective analysis of 19 autologous stem cell transplants (ASCT) with combined BM-PBPC for poor initial PBPC collection was carried out. Mobilization was with filgrastim (10 microg/kg/day) alone for 5 days or after chemotherapy. BM was harvested if PBPC collections were CD34+<2.5 x 10(6)/kg. RESULTS: The median age was 55 years (range 19-74). The diagnoses were multiple myeloma (7), non-Hodgkin's lymphoma (7), Hodgkin's disease (4) and acute myeloid leukemia (1). The median cell content (CD34+/kg x 10(6)) was 1.1 (0.3-2.7) for BM, 1.2 (0.04-2.8) for PBPC and 2.2 (1.4-4.9) combined. Eight grafts contained <2.0 x 10(6) CD34+/kg (1.4-1.8). The median engraftment in days (range) was: absolute neutrophil count (ANC) > 500, 12 (9-39); Plt > 20 000, 25 (15-70); RBC transfusion independence, 17 (6-93). Six patients died of progressive disease (58-293 days post-ASCT), one of infection on day 141 and one of AML on day 11. All patients except one maintained ANC > 1000 without filgrastim support beyond day 19. One patient had cholecystitis and delayed graft failure on day 90. PBPC CD34+ content did not predict CD34+ BM content but correlated with ANC > 500 (r= - 0.64, P=0.003). BM and combined CD34+ and BM TNC/kg did not correlate with engraftment or outcomes. Combined CD34+/kg < or > = 2.0 x 10(6) produced similar engraftment and mortality. CONCLUSIONS: After a failed PBPC collection, BM harvest is a reliable option for obtaining an adequate combined autograft. Combined BM-PBPC autografts with <2.0x10(6) CD34+/kg can produce satisfactory engraftment.

Psychological distress in long-term survivors of hematopoietic stem cell transplantation.

The prevalence of psychological distress is higher in cancers with poorer prognoses and speculated as higher in those receiving more aversive treatments. Since hematopoietic stem cell transplant (HSCT) is one of the most taxing cancer treatments to endure and is therefore likely to have more long-term sequelae, this study examined psychological distress symptoms in long-term HSCT survivors who were at least 1 year post-transplant. Participants in this cross-sectional study were recruited from urban medical centers as part of a larger study of HSCT survivors. The sample comprised 236 adults who were on average 3.4 years since transplant. Psychological distress was measured by a commonly used self-report questionnaire, the Brief Symptom Inventory. Clinically elevated psychological distress caseness was present in 43% of long-term HSCT survivors. Elevations were highest on clinical subscales of obsessive-compulsiveness, somatization, and psychoticism. However, item-level analyses revealed that the content of the most frequently reported symptoms included trouble with memory and feelings of loneliness. Results of this study suggest that HSCT survivors may experience memory and existential concerns and that such symptoms may not represent psychiatric sequelae.

Graft versus host disease after stem cell allotransplantation with low-dose total body irradiation, fludarabine, and antithymocyte globulin.

BACKGROUND: We previously showed that antithymocyte globulin (ATG) given with total body irradiation (TBI) 200 cGy and fludarabine results in high rate of donor engraftment. Its influence on acute and chronic graft versus host disease (GVHD) and on graft versus tumor effect is less known. METHODS: Sixty-five patients underwent nonmyeloablative stem cell transplant with ATG, TBI 200 cGy, and fludarabine. GVHD prophylaxis was mycophenolate mofetil and cyclosporine. Forty-two patients (pts) (65%) had match related donors, 18 (27%) match unrelated, 1 (1.5%) mismatch related, and 4 (6%) mismatch unrelated donors. RESULTS: At a median follow-up of 862 days, 24 patients (37%) developed GVHD. The median age of the patients with and without GVHD was 56 years respectively. Acute GVHD grade II-IV developed in 19 pts (29%). Fatal GVHD of liver and/or gut occurred in nine pts (14%). Forty-one pts survived more than 100 days. Five pts (12%) had chronic GVHD, two had extensive, and three had limited involvement. Relapsed disease was observed in 22 pts (34%). Infections occurred in 15 pts (23%) and were fatal in 13 (20%). CONCLUSIONS: The addition of ATG to TBI 200cGy and fludarabine resulted in a modest incidence of GVHD. The best transplant outcomes were observed in pts with lymphoid malignancies.

Lymph nodes can accurately be measured on PET-CT for lymphoma staging/restaging without a concomitant contrast enhanced CT scan.

Dual imaging with both contrast enhanced CT scan and PET-CT is recommended for evaluation of lymphoma. We compared the performance in identification and size measurements of involved lymph nodes in FDG-avid lymphomas on the low dose non-contrast enhanced CT of a PET-CT scan with those on a diagnostic contrast enhanced CT scan. The size of FDG-avid lymph nodes was measured in both the short and long axis on both the low dose non-contrast CT of the PET-CT and the contrast enhanced CT by two independent readers. A total of 307 FGD avid lymph nodes were identified in 52 patients. There was no statistically significant differences in the measured size of the nodes on the non-contrast and contrast enhanced scans (p=0.21). Baseline staging and restaging of FDG-avid lymphomas can be performed with one test, PET-CT, without an accompanying contrast enhanced CT scan, with no effect on the measured nodal size.

Construct validity of the posttraumatic stress disorder checklist in cancer survivors: analyses based on two samples.

The measurement of posttraumatic stress disorder (PTSD) is critically important for the identification and treatment of this disorder. The PTSD Checklist (PCL; F. W. Weathers and J. Ford, 1996) is a self-report measure that is increasingly used. In this study, the authors investigated the factorial validity of the PCL with data from 236 cancer survivors who received a bone marrow or stem cell transplantation. The authors examined the fit of these data with the clinical model of 3 symptom clusters for PTSD, as proposed in the Diagnostic and Statistical Manual of Mental Disorders, and alternative models tested in prior research. By using confirmatory factor analysis the authors found that a 4-first-order-factor model of PTSD provided the best fit. The relations of PTSD symptoms with sociodemographic and medical variables were also explored.

Retrospective analysis of prognosticators in patients with relapsed Hodgkin's Lymphoma treated with autologous transplant: results of a single center.

Hodgkin's Lymphoma (HL) is highly chemoresponsive, and majority of patients respond to therapy except for a small number which require high-dose therapy and stem cell rescue for salvage. We report the results of a single-center experience in 41 patients with relapsed HL treated with high-dose therapy at the time of relapse from the year 1989-2010. The 7-year OS for the group is 39.2 %; the median progression-free survival is 30.6 months. Univariate analysis identified refractory disease at transplant and extranodal involvement as important prognosticators. The 100-day mortality was 5 %. The most common cause for delayed mortality was disease progression. The incidence of secondary malignancy in the group was 2 %. Our results reinforce the significance of long-term follow up as late relapses are observed. Additionally, identifying biological prognosticators and implying them for treatment may improve the outcomes in poor-risk patients.

Effectiveness of partner social support predicts enduring psychological distress after hematopoietic stem cell transplantation.

OBJECTIVE: Hematopoietic stem cell transplant (HSCT) survivors who are 1 to 3 years posttransplant are challenged by the need to resume valued social roles and activities--a task that may be complicated by enduring transplant-related psychological distress common in this patient population. The present study investigated whether transplant survivors who receive adequate social support from their spouse or intimate partner experience lower distress. METHOD: Effects of receiving a greater quantity of partner support (a common approach to studying enacted support) were compared with effects of receiving more effective partner support (i.e., support that more closely matches their needs in terms of its quantity and quality). Men and women (N = 230) who were 1 to 3 years posttransplant completed measures of partner support quantity (Manne & Schnoll, 2001), partner social support effectiveness (Rini & Dunkel Schetter, 2010), and psychological distress (Brief Symptom Inventory; Derogatis & Spencer, 1982). Potential medical and sociodemographic confounds were controlled in analyses. RESULTS: As hypothesized, survivors reported less distress when they received more effective partner support (p < .001). Quantity of partner support was not associated with distress (p = .23). An interaction revealed that when partner support was effective, the quantity of support survivors received was not associated with their distress (p = .90); however, when partner support was ineffective, receiving a greater quantity of partner support was associated with substantially elevated distress (p = .002). CONCLUSIONS: Findings suggest that clinical approaches to addressing or preventing enduring distress after HSCT should target features of partner support related to its appraised effectiveness.

Randomized clinical trial of telephone-administered cognitive-behavioral therapy to reduce post-traumatic stress disorder and distress symptoms after hematopoietic stem-cell transplantation.

PURPOSE: A significant number of survivors of hematopoietic stem-cell transplantation (HSCT) report enduring adverse effects of treatment, including illness-related post-traumatic stress disorder (PTSD) symptoms and general distress. We report results of a randomized clinical trial that tested the effects of a 10-session, telephone-administered cognitive-behavioral therapy (CBT) intervention on PTSD, depression, and distress symptoms. METHODS: Survivors who had undergone HSCT 1 to 3 years earlier (N = 408) were assessed for study eligibility. Those who met study eligibility criteria (n = 89) completed a baseline assessment that included a clinical interview and self-report measures of PTSD symptoms (the primary outcome) and depression and general distress (the secondary outcomes). Next, they were randomly assigned to CBT or an assessment-only condition. Survivors in the CBT group completed 10 individual telephone-based CBT sessions (T-CBT) that included strategies to reduce PTSD symptoms, depression, and general distress. Follow-up assessments occurred at 6, 9, and 12 months after the baseline assessment. RESULTS: Linear mixed-model analyses revealed that, compared with HSCT survivors in the assessment-only condition, survivors who completed T-CBT reported fewer illness-related PTSD symptoms, including less avoidance (P < .001) and fewer intrusive thoughts (P < .05) as well as less general distress and fewer depressive symptoms (P < .05) even after controlling for potential demographic and medical covariates. These results were consistent across the three follow-up assessments. CONCLUSION: A brief, telephone-administered CBT intervention developed for HSCT survivors is an efficacious treatment for reducing illness-related PTSD symptoms and general distress.

Low-dose total body irradiation, fludarabine, and antithymocyte globulin conditioning for nonmyeloablative allogeneic transplantation.

Nonmyeloablative allogeneic peripheral blood progenitor cell transplantation with low-dose total body irradiation (TBI; 200 cGy) plus fludarabine followed by cyclosporine and mycophenolate mofetil results in modest graft rejection rates. Acute and chronic graft-versus-host diseases (GVHD) are also seen and may not differ substantially from those that occur after fully ablative transplantation. Adding antithymocyte globulin (ATG) to pretransplant conditioning produces substantial immunosuppression. Because of its persistence in the circulation, ATG can achieve in vivo T-cell depletion. Twenty-five patients who were not eligible for conventional fully ablative allogeneic stem cell transplantation by virtue of age or comorbidities underwent nonmyeloablative allogeneic transplantation with ATG 15 mg/kg/d days -4 to -1, TBI 200 cGy on a single fraction on day -5, and fludarabine 30 mg/m(2)/d on days -4 to -2. Oral mycophenolate mofetil 15 mg/kg every 12 hours and cyclosporine 6 mg/kg every 12 hours were started on day -5. Grafts were unmanipulated peripheral blood progenitor cells mobilized with filgrastim 10 microg/kg/d and collected on day 5. The median age of the recipients was 57 years (range, 30-67 years); diagnoses were non-Hodgkin lymphoma (n = 11), acute myeloid leukemia (n = 6), multiple myeloma (n = 3), acute lymphoblastic leukemia (n = 2), severe aplastic anemia (n = 1), paroxysmal nocturnal hemoglobinuria (n = 1), and myelodysplastic syndrome (n = 1). The median CD34(+) and CD3(+) contents of the grafts were 7.6 x 10(6)/kg and 1.6 x 10(8)/kg, respectively. Five patients received voluntary unrelated donor grafts. Three patients, 2 with voluntary unrelated donor grafts and 1 with a sib donor, received a 1 antigen-mismatched graft. The rest were fully matched. Twenty-two of 25 patients were evaluable for chimerism. Sixteen had >/=95% donor chimerism. Four patients displayed 80% to 90% donor chimerism, 1 displayed 78%, and 1 displayed 64%. Eleven patients relapsed with their original disease. One patient rejected the graft at 180 days. The median hospital stay was 27 days. Complications included GVHD in 6 patients (3 patients had grade I or II GVHD of skin and liver, and 3 patients had grade III or IV GVHD of liver and gut). Two of the patients with GVHD had mismatched grafts. Transplant-related toxicity was seen in 4 patients and infection in 5 patients. The median length of follow-up was 162 days (range, 17-854 days). Complete remissions were seen in 10 patients. Four patients remained in complete response (CR) at 280 to 595 days. One patient relapsed with non-Hodgkin lymphoma after a CR of 728 days. Of the 25 patients, 16 died (6 of relapsed disease, 4 of GVHD, 3 of infection, and 3 of transplant-related toxicity) and 9 are alive (6 with CR-2 of them after donor leukocyte infusion-and 3 with relapsed disease). The addition of ATG to low-dose TBI and fludarabine nonmyeloablative conditioning was well tolerated and resulted in >80% donor engraftment in this small cohort. As in other series of truly nonmyeloablative transplantation, a high rate of relapse was observed. Donor engraftment may be facilitated by the addition of ATG to low-dose TBI and fludarabine conditioning.