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Summary This study examined barriers to mental health service use and their demographic, medical, and psychosocial correlates among hematopoietic stem cell transplant (HSCT) survivors. A sample of 253 HSCT survivors who were 1- to 3-years post-transplant completed measures of demographic, physical, psychological, and social characteristics as well as a newly modified measure of barriers to mental health service use. Only 50% of distressed HSCT survivors had received mental health services. An exploratory factor analysis of the barriers to mental health service use scale yielded four factors: Scheduling Barriers, Knowledge Barriers, Emotional Barriers, and Illness-related Barriers. Patients with higher social constraints (perceived problems discussing the illness experience with significant others) reported higher levels of all four types of barriers. General distress and transplant-related posttraumatic stress symptoms were positively associated with emotional, knowledge, and illness-related barriers to mental health service use, whereas physical and functional well-being were inversely associated with these barriers. Having more knowledge barriers and more emotional barriers predicted a lower likelihood of receiving mental health services, as did lower levels of education and general distress. Results suggest that a significant number of HSCT survivors may benefit from education about mental health services that is tailored to individual barriers.

In this study, we explored dermal dendritic cell (DC) homeostasis in mice and humans both in the steady state and after hematopoietic cell transplantation. We discovered that dermal DCs proliferate in situ in mice and human quiescent dermis. In parabiotic mice with separate organs but shared blood circulation, the majority of dermal DCs failed to be replaced by circulating precursors for >6 mo. In lethally irradiated mice injected with donor congenic bone marrow (BM) cells, a subset of recipient DCs remained in the dermis and proliferated locally throughout life. Consistent with these findings, a large proportion of recipient dermal DCs remained in patients' skin after allogeneic hematopoietic cell transplantation, despite complete donor BM chimerism. Collectively, our results oppose the traditional view that DCs are nondividing terminally differentiated cells maintained by circulating precursors and support the new paradigm that tissue DCs have local proliferative properties that control their homeostasis in the steady state. Given the role of residual host tissue DCs in transplant immune reactions, these results suggest that dermal DC homeostasis may contribute to the development of cutaneous graft-versus-host disease in clinical 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 in80% 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.

We report a case of a 67-year-old male who underwent OLT from a deceased, sex-matched donor. Two months later he developed Evans syndrome and GVHD of the skin. Donor and recipient were matched for HLA-A and -B loci in the direction of rejection but mismatched in the direction of GVHD and fully mismatched for DRB1. These mismatches were permissible for engraftment of donor T-cells but led to GVHD. Chimerism appeared restricted to the T-cell compartment. In this case, partially matched passenger lymphocytes triggered a graft versus host reaction. In addition, alloantibodies caused cytopenias that improved after immunosuppression. HLA typing was critical in confirming this rare diagnosis and elucidating its cause. Recipients of solid organs from donors that are partially matched in the direction of rejection may need to be closely monitored for GVHD.

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.

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.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.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 contained2.0 x 10(6) CD34+/kg (1.4-1.8). The median engraftment in days (range) was: absolute neutrophil count (ANC)500, 12 (9-39); Plt20 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 ANC1000 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 ANC500 (r= - 0.64, P=0.003). BM and combined CD34+ and BM TNC/kg did not correlate with engraftment or outcomes. Combined CD34+/kgor= 2.0 x 10(6) produced similar engraftment and mortality.After a failed PBPC collection, BM harvest is a reliable option for obtaining an adequate combined autograft. Combined BM-PBPC autografts with2.0x10(6) CD34+/kg can produce satisfactory engraftment.

Abstract 4534 Myelofibrosis is a clonal myeloproliferative disorder, characterized by ineffective hematopoesis and bone marrow fibrosis. The disease can present de novo or secondary to an antecedent chronic myeloproliferative neoplasm such as essential thrombocythemia (ET) or polycythemia vera (PV). Allogeneic hematopoetic stem cell transplantation (AHSCT) is a curative approach for myelofibrosis, and produces durable donor engraftment and regression of myelofibrosis in approximately 50% of eligible patients. We retrospectively evaluated 31 consecutive patients that were treated for MF with AHSCT at our institution between 1998 and 2011. Thirty-one patients, 33 to 70 years of age, with a median age of 47, males 17 and females 14 with primary myelofibrosis or myelofibrosis evolving from antecedent polycythemia vera 4 (12%) or essential thrombocythemia 10 (32%) received AHSCT. Seven (22%) patients had transformed to acute myeloid leukemia prior to transplant. JAK 2 V617F was present in 15 patients, 9 patients were JAK 2 wild type, 5 patients were not tested and 2 were unknown. Patients received AHSCT from related (n= 11) or unrelated (n= 20) donors. Fourteen patients (45%) had a normal karyotype, 16 patients (51%) had an abnormal karyotype and one was unknown. Twenty eight patients received reduced intensity conditioning regimen and three received a fully ablative transplant. The source of stem cells was marrow in 4 patients and peripheral blood in 27 patients. Median time to neutrophil engraftment was 13 days in 28 patients (90%) and three patients had primary graft failure and were re-transplanted. One of the patients receiving a second AHSCT is alive and in complete hematological remission 19 months post-transplant.Twenty-eight patients showed 95–100% donor chimerism at day 30. Two patients had mixed chimerism at day 90. Twenty-six patients (83%) survive more than 100 days, 3 patients died (10%) from relapsed/progressive disease, and 5 (16%) from TRM. However at a median follow up of 31 months post-transplant 15 patients (48%)survived, 11 (45%)with chronic myelofibrosis, and 4 out of 7(57%)who had transformed to AML prior to transplant. Of note all five patients who were greater than 65 years of age at the time of transplant engrafted and enjoyed full hematological and clinical remission, one of these individuals subsequently died of a solid tumor. In addition, one of the patients with AML had an extramedullary relapsed 36 months post-transplant. One of the unanticipated complications observed in these patients who underwent AHSCT was massive peripheral edema in some cases anasarca of unclear etiology that required diuresis and albumin infusions and that occasionally preceded the date of engraftment and persisted for several weeks after engraftment. We conclude that AHSCT is an important therapeutic modality for not only PMF patients 65 years of age and individuals with blastic transformation of MF. Disclosures: No relevant conflicts of interest to declare.

The addition of rituximab to mobilization regimens does not adversely affect collection of adequate numbers of CD34+ PBSC and may decrease tumor cell contamination. Prior administration of rituximab may sensitize lymphoma cells to chemotherapy, but its use with high dose chemotherapy has not been studied. In this study, eligible patients had intermediate grade NHL either primary refractory, relapsed or in CR1 with an intermediate/high risk IPI score. Eight patients with a median age of 49 years (28–61) were enrolled in this study. Four patients had relapsed disease, chemosensitive to salvage in 3 patients, and untested in 1 patient. Two patients had primary refractory disease, chemosensitive to salvage. Two patients had intermediate-high risk IPI scores and were in CR-1. One patient in CR-1 declined to undergo transplant following stem cell collection. All patients had received rituximab previously. Stem cell mobilization was rituximab 375mg/M2 followed by CY 2gm/M2/day for 2 doses and filgrastim 10ug/kg/d. High dose chemotherapy consisted of rituximab 375mg/M2 on day -8, carmustine 300mg/M2 on day -7, etoposide 200mg/M2/d on days -6 to -3, cytosine arabinoside 200mg/M2 on days -6 to -3 (8 doses) and melphalan 140mg/M2 on day -2. Patients received filgrastim post transplant. RESULTS: The median CD34+ cell dose collected was 12.5 x 106/kg (1.1 to 33.2). There was one inadequate CD34+ cell collection requiring bone marrow harvesting which yielded 0.72 x 106/kg CD34+ cells. Engraftment of neutrophils and platelets occurred at a median of 8 and 11 days post transplant respectively. Infectious complications included febrile neutropenia in one patient following mobilization and in 6 patients following R-BEAM. Transient grade I–II (common toxicity criteria) hepatic enzyme elevation occurred in 2 patients following R-CY. Following R-BEAM, 3 patients developed grade II-IV LFT elevation without evidence of VOD, which resolved. One patient developed moderate hemorrhagic cystitis which resolved. One patient developed bilateral pulmonary infiltrates of unkown etiology (BAL negative for organisms) which resolved. Immunoglobulin levels remained normal in two patients, but decreased in all other patients for up to a year post transplant. Peripheral blood flow cytometry and T cell subset analysis showed absent B cell populations, decreased CD4 cells and increased CD 8 cells in all patients up to a year post transplant. Five patients are alive with no evidence of disease 381 to 676 days post transplant. Three of these patients developed PET positive lymph nodes that showed florid follicular hyperplasia on biopsy, with no evidence of lymphoma. Two patients had persistent disease following transplant. One patient underwent a non-myeloablative allogeneic transplant and died of progressive disease. CONCLUSIONS: R-CY was well tolerated as a mobilization regimen and led to adequate stem cell collection. The addition of rituximab to the high dose chemotherapy regimen did not appear to increase the incidence of infections or peritransplant complications in this Phase I study. The effect, on disease free survival, of the addition of rituximab to the collection and preparative regimens requires further investigation.

Acute GvHD is a frequent complication of non-myeloablative transplantation although it is seen at a lower rate and severity than after myeloablative transplantation. The use of ATG in transplant conditioning produces substantial host immunosuppression. Furthermore, the persistence of ATG in the circulation after transplantation is thought to accomplish an in-vivo T-cell depletion of the stem cell inoculum. Non-myeloablative stem cell transplantation using low dose TBI (200cGy) and fludarabine results in a high rate of full donor chimerism. We previously showed that the addition of ATG to TBI 200 cGy and fludarabine can improve donor engraftment. Whether it also impacts on acute and chronic GvHD and on graft versus tumor effect is less known. Forty-seven patients, not eligible for conventional fully ablative allogeneic SCT by virtue of age or co-morbidities, underwent non-myeloablative allogeneic transplantation using ATG 15 mg/kg/day (equine) or 1.5mg/kg/day (rabbit) days −4 to −1, TBI 200 cGy on a single fraction on day −5, fludarabine 30 mg/kg/day on days −4 to −2. Oral immunosuppression with MMF and CSA were started on day −5. Allografts were unmanipulated peripheral blood progenitor cells collected on day 5 of mobilization with filgrastim 10 mcg/kg/day. Thirty-two patients (68%) had match related donors, 9 (19%) match unrelated (10/10), 1(2%) mismatch related (9/10) and 5 (10.6%) mismatch unrelated donors (9/10). Twenty-five patients had sex matched donors (53.2%). Full donor chimerism was documented in 85% and partial (>50%) in 11% of patients. At a median follow up of 309 days, graft versus host disease grade II–IV developed in 13 patients (27.6%). Fatal GvHD of liver and/or gut occurred in 8 patients (17%). The mean age of patients who developed GvHD was 54 years and 57 for those who did not (p=ns). The corresponding mean ages for their donors were 47 vs. 50 years (p=ns). Seven out of fourteen (50%) unrelated transplants recipients and 6/33 (18%) with related donors develop GVHD (p=0.023). Infectious complications were seen in 8 patients (17%) and were the cause of death in 6 (12%). Thirteen of the 47 patients (27.6%) underwent transplant for AML. Six patients had relapsed/refractory disease at the time of transplant, 3 were in CR2 and 4 in CR1. Eleven patients (84.6%) relapsed with AML after transplant. Previously reported data on non-myeloablative stem cell transplant using 200 cGy of TBI and fludarabine with no ATG showed an incidence of acute GvHD grade II–IV of 64% and 24% GvHD related mortality. Similar rates have been reported with fludarabine and melphalan reduced-intensity conditioning. In our cohort of 47 patients the addition of ATG resulted in decreased incidence of acute GvHD grade II–IV and GvHD related mortality without a high rate of infectious complications. A high incidence of disease relapse in patients with AML may reflect the high proportion of patients with advanced leukemia enrolled in the study. However, it also warrants further investigation to rule out that ATG may hinder graft versus leukemia effect.

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/m2/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