Effective treatment with the selective cytokine inhibitor BNZ-1 reveals the cytokine dependency of T-LGL leukemia.

T-cell large granular lymphocytic leukemia (T-LGLL) is a clonal proliferation of cytotoxic T lymphocytes that can result in severe neutropenia, anemia, and bone marrow failure. Strong evidence from patients and mouse models demonstrate the critical role of interleukin-15 (IL-15) in T-LGLL pathogenesis. BNZ-1 is a pegylated peptide that selectively inhibits the binding of IL-15 and other γc cytokines to their cellular receptor complex, which has demonstrated efficacy in ex vivo T-LGLL cells and transgenic mice in preclinical studies. We conducted a phase 1/2 trial of BNZ-1 in patients with T-LGLL who had hematocytopenias (anemia or neutropenia) and required therapy. Clinical responses were assessed using hematologic parameters (improvement in hematocytopenias) based on response criteria from the Eastern Cooperative Oncology Group 5998 T-LGLL trial. BNZ-1 demonstrated clinical partial responses in 20% of patients with T-LGLL with minimal toxicity and the maximum tolerated dose was not reached. Furthermore, T-LGL leukemic cells showed significantly increased apoptosis in response to BNZ-1 treatment as early as day 2, including in clinical nonresponders, with changes that remained statistically different from baseline throughout treatment (P < .005). We report first-in-human proof that T-LGL leukemic cells are dependent on IL-15 and that intervention with IL-15 inhibition with BNZ-1 in patients with T-LGLL shows therapeutic effects, which carries important implications for the understanding of the pathogenesis of this disease. This trial was registered at www.clinicaltrials.gov as #NCT03239392.

Myeloid neoplasm with histiocytosis and spleen tyrosine kinase fusion responds to fostamatinib.

Not available.

Impact of conditioning regimen intensity on the outcomes of peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma patients undergoing allogeneic transplant.

There have been no large studies comparing reduced-intensity/non-myeloablative conditioning (RIC/NMA) to myeloablative conditioning (MAC) regimens in T-cell non-Hodgkin lymphoma (T-NHL) patients undergoing allogeneic transplant (allo-HCT). A total of 803 adults with peripheral T-cell lymphoma, anaplastic large cell lymphoma and angioimmunoblastic T-cell lymphoma (age 18-65 years), undergoing allo-HCT between 2008-2019 and reported to the Center for International Blood and Marrow Transplant Research with either MAC (n = 258) or RIC/NMA regimens (n = 545) were evaluated. There were no significant differences between the two cohorts in terms of patient sex, race and performance scores. Significantly more patients in the RIC/NMA cohort had peripheral blood grafts, haematopoietic cell transplantation-specific comorbidity index (HCT-CI) of ≥3 and chemosensitive disease compared to the MAC cohort. On multivariate analysis, overall survival (OS) was not significantly different in the RIC/NMA cohort compared to the MAC cohort (hazard ratio (HR) = 1.01, 95% confidence interval (CI) = 0.79-1.29; p = 0.95). Similarly, non-relapse mortality (NRM) (HR = 0.85, 95% CI = 0.61-1.19; p = 0.34), risk of progression/relapse (HR = 1.29; 95% CI = 0.98-1.70; p = 0.07) and therapy failure (HR = 1.14; 95% CI = 0.92-1.41, p = 0.23) were not significantly different between the two cohorts. Relative to MAC, RIC/NMA was associated with a significantly lower risk of grade 3-4 acute graft-versus-host disease (HR = 0.67; 95% CI = 0.46-0.99, p = 0.04). Among chemorefractory patients, there was no difference in OS, therapy failure, relapse, or NRM between RIC/NMA and MAC regimens. In conclusion, we found no association between conditioning intensity and outcomes after allo-HCT for T-cell NHL.

T-Cell Lymphomas, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of lymphoproliferative disorders arising from mature T cells, accounting for about 10% of non-Hodgkin lymphomas. PTCL-not otherwise specified is the most common subtype, followed by angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma, anaplastic lymphoma kinase-positive, anaplastic large cell lymphoma, anaplastic lymphoma kinase-negative, and enteropathy-associated T-cell lymphoma. This discussion section focuses on the diagnosis and treatment of PTCLs as outlined in the NCCN Guidelines for T-Cell Lymphomas.

Clinical outcomes in T-cell large granular lymphocytic leukaemia: prognostic factors and treatment response.

T-cell large granular lymphocytic leukaemia (T-LGLL) is an incurable leukaemia characterised by clonal proliferation of abnormal cytotoxic T cells that can result in severe neutropenia, transfusion-dependent anaemia and pancytopenia requiring treatment. The most commonly used agents, methotrexate (MTX), cyclophosphamide (Cy) and cyclosporine primarily produce partial remissions (PRs), with few complete responses (CRs). We evaluated the clinical course and treatment response of 60 consecutive patients with T-LGLL to evaluate clinical outcomes and future potential treatment directions. Impaired overall survival was noted among male patients, patients with elevated lactate dehydrogenase, and those without rheumatoid arthritis. Cy was the most efficacious second-line agent, with a 70% overall response rate (ORR; three CR, four PR). All patients who failed frontline MTX responded to second-line Cy. In the relapsed or Cy-refractory setting, alemtuzumab (n = 4) and pentostatin (n = 3) had an ORR of 50% and 66%, respectively, while duvelisib induced a long-term response in one patient. In this large, retrospective analysis, our results suggest Cy is a highly effective therapy for second-line treatment in T-LGLL and should be considered a strong candidate for up-front therapy in select high-risk patients. Prospective studies evaluating pentostatin, alemtuzumab and novel agents, such as duvelisib, are needed for patients with relapsed/refractory T-LGLL.

Rapid progression of adult T-cell leukemia/lymphoma as tumor-infiltrating Tregs after PD-1 blockade.

Immune checkpoint inhibitors are a powerful new tool in the treatment of cancer, with prolonged responses in multiple diseases, including hematologic malignancies, such as Hodgkin lymphoma. However, in a recent report, we demonstrated that the PD-1 inhibitor nivolumab led to rapid progression in patients with adult T-cell leukemia/lymphoma (ATLL) (NCT02631746). We obtained primary cells from these patients to determine the cause of this hyperprogression. Analyses of clonality, somatic mutations, and gene expression in the malignant cells confirmed the report of rapid clonal expansion after PD-1 blockade in these patients, revealed a previously unappreciated origin of these malignant cells, identified a novel connection between ATLL cells and tumor-resident regulatory T cells (Tregs), and exposed a tumor-suppressive role for PD-1 in ATLL. Identifying the mechanisms driving this alarming outcome in nivolumab-treated ATLL may be broadly informative for the growing problem of rapid progression with immune checkpoint therapies.

Autologous EBV-specific T cell treatment results in sustained responses in patients with advanced extranodal NK/T lymphoma: results of a multicenter study.

We conducted a phase II clinical trial to develop an autologous EBV-specific T cell product (baltaleucel T) for advanced, relapsed ENKTL. Among 47 patients who provided whole blood starting material for manufacturing the product, 15 patients received a median of 4 doses of baltaleucel T. Thirty-two (68%) patients did not receive baltaleucel-T due to manufacturing failure, rapid disease progression, and death. Of the 15 patients, 10 patients had measurable disease at baseline (salvage cohort), and 5 patients had no disease at baseline assessment (adjuvant cohort). In the 15 patients, the median follow-up duration was 10.2 months (range 2.0-23.5 months), median progression-free survival (PFS) was 3.9 months, and the median overall survival (OS) was not reached. Patients in the salvage cohort achieved a 30% complete response (CR) and a 50% overall response rate (ORR). In the adjuvant cohort, disease progression was reported in three patients and two patients did not relapse during study follow-up. When we compared survival outcomes of seven responders and eight non-responders, the PFS (P = 0.001) and OS (P = 0.014) of responders proved statistically superior to that of non-responders. Baltaleucel-T was well tolerated. We have performed a phase II clinical trial of autologous EBV-specific T cell treatment (baltaleucel-T) in R/R ENKTL. Autologous EBV-specific T cells were well tolerated and demonstrated single-agent activity in R/R ENTKL.

Aging Phenotypes and Restoring Functional Deficits in Older Adults With Hematologic Malignancy.

BACKGROUND: Gauging fitness remains a challenge among older adults with hematologic malignancies, and interventions to restore function are lacking. We pilot a structured exercise intervention and novel biologic correlates of aging using epigenetic clocks and markers of immunosenescence to evaluate changes in function and clinical outcomes. METHODS: Older adults (n=30) with hematologic malignancy actively receiving treatment were screened and enrolled in a 6-month exercise intervention, the Otago Exercise Programme (OEP). The impact of the OEP on geriatric assessment metrics and health-related quality of life were captured. Clinical outcomes of overall survival and hospital utilization (inpatient length of stay and emergency department use) in relationship to geriatric deficits were analyzed. RESULTS: Older adults (median age, 75.5 years [range, 62-83 years]) actively receiving treatment were enrolled in the OEP. Instrumental activities of daily living and physical health scores (PHS) increased significantly with the OEP intervention (median PHS: visit 1, 55 [range, 0-100]; visit 2, 70 [range, 30-100]; P<.01). Patient-reported Karnofsky performance status increased significantly, and the improvement was sustained (median [range]: visit 1, 80 [40-100]; visit 3, 90 [50-100]; P=.05). Quality of life (Patient-Reported Outcome Measurement Information System [PROMIS]) improved significantly by the end of the 6-month period (median [range]: visit 1, 32.4 [19.9-47.7]; visit 3, 36.2 [19.9-47.7]; P=.01]. Enhanced measures of gait speed and balance, using the Short Physical Performance Battery scores, were associated with a 20% decrease in risk of death (hazard ratio, 0.80; 95% CI, 0.65-0.97; P=.03) and a shorter hospital length of stay (decrease of 1.29 days; 95% CI, -2.46 to -0.13; P=.03). Peripheral blood immunosenescent markers were analyzed in relationship to clinical frailty and reports of mPhenoAge epigenetic analysis are preliminarily reported. Chronologic age had no relationship to overall survival, length of stay, or emergency department utilization. CONCLUSIONS: The OEP was effective in improving quality of life, and geriatric tools predicted survival and hospital utilization among older adults with hematologic malignancies.

Fluoroquinolone Prophylaxis in Autologous Stem Cell Transplantation: Worthy of a Second Look.

Prophylaxis with fluoroquinolone (FQ) for patients undergoing autologous stem cell transplantation (ASCT) remains controversial. We performed a retrospective review of patients undergoing ASCT with and without bacterial prophylaxis to compare endpoints of interest. In accordance with institutional policy, patients undergoing ASCT for multiple myeloma routinely receive levofloxacin prophylaxis during their period of neutropenia, whereas patients undergoing the ASCT for lymphoma do not. We retrospectively examined patients with multiple myeloma (MM) or lymphoma undergoing ASCT between July 2015 and July 2018 for evidence of positive blood cultures. A total of 172 patients underwent ASCT for lymphoma and 343 underwent ASCT for MM. The 2 cohorts were similar in terms of baseline characteristics. Almost 20% (35 of 172) of the patients with lymphoma and 5.2% (18 of 342) of those with MM had a bloodstream infection (BSI). BSI occurred an average of 2 days earlier in patients with lymphoma compared with patients with MM (day +5 versus day +7; P = .0003). The 2 cohorts recovered absolute neutrophil count at the same time. Hospital length of stay was 2 days shorter for patients with MM (median, 20 days versus 18 days; P = .01). The majority of the organisms were gram-negative in both cohorts. Of the organisms commonly tested for FQ sensitivity, only 1 of 25 was resistant in the lymphoma cohort, compared with 7 of 9 in the MM cohort (P < .0001), with 4 being multidrug resistant. The odds of developing a BSI were 4.6 times greater in the lymphoma cohort compared with the MM cohort (95% confidence interval [CI], 2.52 to 8.40; P < .0001). In total, 23 of 172 patients with lymphoma (13.4%) and 28 of 342 patients with MM (8.2%) developed Clostridium difficile infection (odds ratio, 1.73; 95% CI, .96 to 3.11; P = .066). Two infection-related deaths occurred in the MM cohort. Our data indicate that FQ prophylaxis reduces the risk of BSI in patients undergoing ASCT but increases the incidence of resistant organisms. We recommend routine antimicrobial prophylaxis in patients undergoing ASCT to reduce the risk of BSI, along with a systematic and regular review of outcomes.

Relapse risk and survival in patients with FLT3 mutated acute myeloid leukemia undergoing stem cell transplantation.

In patients with AML with FMS-like tyrosine kinase 3 (FLT3) mutations, the significance of minimal residual disease (MRD) detected by PCR before allogeneic stem cell transplantation (SCT) on outcomes after transplant remains unclear. We identified 200 patients with FLT3-AML who underwent SCT at our institution. Disease status at transplant was: first or second complete remission (CR1/CR2, n = 119), high-risk CR (third or subsequent CR, marrow hypoplasia, or incomplete count recovery) (CR-HR, n = 31), and morphological evidence of active disease (AD, n = 50). The median follow-up was 27 months, and the 2-year overall and progression-free survival were 43% and 41%, respectively. Relapse was highest in the AD group (85%) and the CR-HR FLT3 MRD positive group (72%), followed by CR-HR FLT3 MRD negative (58%), CR1/CR2 FLT3 MRD positive (39%), and lowest in the CR1/CR2 FLT3 MRD negative group (23%). On multivariate analysis, independent factors influencing the risk of relapse were detectable morphological disease and FLT3 MRD by PCR pre-transplant. Factors that did not influence the relapse risk included: age, graft type, graft source, type of FLT3 mutation, or conditioning intensity. Morphologic and molecular remission status at the time of transplant were key predictors of disease relapse and survival in patients with FLT3-AML.

Outcomes of Haploidentical Stem Cell Transplantation for Lymphoma with Melphalan-Based Conditioning.

Haploidentical transplantation (Haplo-SCT) with post-transplantation cyclophosphamide (PTCy) is increasingly utilized for the treatment of lymphoma and almost exclusively with the nonmyeloablative fludarabine (Flu)/cyclophosphamide/total body irradiation (TBI) conditioning regimen. We present early results of a reduced-intensity (RIC) regimen utilizing fludarabine and melphalan (FM) for the treatment of advanced lymphoma. All patients with a diagnosis of lymphoma or chronic lymphocytic leukemia (CLL) who received Haplo-SCT at the University of Texas MD Anderson Cancer Center between 2009 and 2014 were reviewed (N = 22). Patients received Flu 160 mg/m(2) and melphalan 100 mg/m(2) to 140 mg/m(2) with thiotepa 5 mg/kg or 2 Gy TBI. Because of concerns of increased treatment-related mortality (TRM) with the melphalan 140 mg/m(2) regimen (FM140), a RIC regimen with melphalan 100 mg/m(2) (FM100) was devised. Rituximab was included for CD20(+) disease. Graft-versus-host disease prophylaxis consisted of PTCy 50 mg/kg on days +3 and + 4, tacrolimus, and mycophenolate mofetil. Sixty-eight percent of all patients were not in complete remission at the time of transplantation. The 2-year progression-free survival (PFS) and overall survival (OS) for the entire cohort were 54%, 1-year TRM was 19%, and the cumulative incidence of relapse at 2 years was 27%. Two-year PFS for Hodgkin lymphoma, non-Hodgkin lymphoma, and CLL/small lymphocytic lymphoma were 57%, 51%, and 75%. Patients treated with FM100 compared to FM140 had equivalent PFS (71% versus 37%, P = .246) and OS (71% versus 58%, P = .32). These early results establish Flu and melphalan 100 mg/m(2) with 2 Gy TBI or thiotepa 5 mg/kg as a very promising conditioning regimen for the treatment of advanced lymphoma with Haplo-SCT and PTCy.

Results of a 2-arm, phase 2 clinical trial using post-transplantation cyclophosphamide for the prevention of graft-versus-host disease in haploidentical donor and mismatched unrelated donor hematopoietic stem cell transplantation.

BACKGROUND: High-dose, post-transplantation cyclophosphamide (PTCy) to prevent graft-versus-host disease (GVHD) has improved outcomes in haploidentical (HAPLO) stem cell transplantation (SCT). However, it remains unclear whether this strategy is effective in SCT from 1-antigen human leukocyte antigen (HLA)-mismatched unrelated donors (9/10 MUD) and how the outcomes of these patients compare with those of haploidentical transplantation recipients. METHODS: A parallel, 2-arm, nonrandomized phase 2 clinical trial was conducted of melphalan-based reduced-intensity conditioning with PTCy, tacrolimus, and mycophenolate mofetil to prevent GVHD in patients with high-risk hematologic malignancies who underwent HAPLO (n = 60) or 9/10 MUD (n = 46) SCT. RESULTS: The 1-year overall and progression-free survival rates were 70% and 60%, respectively, in the HAPLO arm and 60% and 47%, respectively, in the 9/10 MUD arm. The day +100 cumulative incidence of grade II to IV acute GVHD and grade III to IV acute GVHD was 28% and 3%, respectively, in the HAPLO arm and 33% and 13%, respectively, in the 9/10 MUD arm. The 2-year cumulative incidence of chronic GVHD was 24% in the HAPLO arm and 19% in the 9/10 MUD arm. The 1-year cumulative incidence of nonrelapse mortality was 21% in the HAPLO arm and 31% in the 9/10 MUD arm, and the 1-year relapse rate was 19% in the HAPLO arm and 25% in the 9/10 MUD arm. CONCLUSIONS: Although this was a nonrandomized study and could not serve as a direct comparison between the 2 groups, the authors conclude that PTCy-based GVHD prophylaxis is effective for both HAPLO and 9/10 MUD SCTs. Prospective randomized trials will be required to compare the efficacies of alternative donor options for patients lacking HLA-matched donors. Cancer 2016;122:3316-3326. © 2016 American Cancer Society.

Allogeneic transplantation provides durable remission in a subset of DLBCL patients relapsing after autologous transplantation.

For diffuse large B-cell lymphoma (DLBCL) patients progressing after autologous haematopoietic cell transplantation (autoHCT), allogeneic HCT (alloHCT) is often considered, although limited information is available to guide patient selection. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 503 patients who underwent alloHCT after disease progression/relapse following a prior autoHCT. The 3-year probabilities of non-relapse mortality, progression/relapse, progression-free survival (PFS) and overall survival (OS) were 30, 38, 31 and 37% respectively. Factors associated with inferior PFS on multivariate analysis included Karnofsky performance status (KPS) <80, chemoresistance, autoHCT to alloHCT interval <1-year and myeloablative conditioning. Factors associated with worse OS on multivariate analysis included KPS<80, chemoresistance and myeloablative conditioning. Three adverse prognostic factors were used to construct a prognostic model for PFS, including KPS<80 (4 points), autoHCT to alloHCT interval <1-year (2 points) and chemoresistant disease at alloHCT (5 points). This CIBMTR prognostic model classified patients into four groups: low-risk (0 points), intermediate-risk (2-5 points), high-risk (6-9 points) or very high-risk (11 points), predicting 3-year PFS of 40, 32, 11 and 6%, respectively, with 3-year OS probabilities of 43, 39, 19 and 11% respectively. In conclusion, the CIBMTR prognostic model identifies a subgroup of DLBCL patients experiencing long-term survival with alloHCT after a failed prior autoHCT.

Outcomes in patients with multiple myeloma with TP53 deletion after autologous hematopoietic stem cell transplant.

TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n = 111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P = 0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P = 0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P = 0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P < 0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P < 0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P < 0.001) and relapsed disease at auto-HCT (hazard ratio 2.0, 95% confidence interval 1.2-3.4, P = 0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto-HCT, TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. Am. J. Hematol. 91:E442-E447, 2016. © 2016 Wiley Periodicals, Inc.

Nonmyeloablative allogeneic hematopoietic stem cell transplant for the treatment of patients with hematologic malignancies using busulfan, fludarabine, and total body irradiation conditioning is effective in an elderly and infirm population.

The BuFluTBI conditioning regimen was designed with the primary goal of reducing non-relapse mortality (NRM) while maximizing primary disease control in patients ineligible for myeloablative conditioning. Patients with hematologic malignancies for whom limited long-term survival was expected with standard therapy were administered an outpatient conditioning regimen of busulfan 3.2 mg/kg IV on day -5, fludarabine 30 mg/m(2) IV on days -4, -3, -2, and 200 cGy of total body irradiation (TBI) followed by stem cell infusion from related or unrelated donors. GVHD prophylaxis included cyclosporine and mycophenolate mofetil. 147 patients were enrolled from 2005-2011; 59% with myeloid disease and 41% with lymphoid disease. The median age was 64, and the median comorbidity index (HCT-CI) score was 3. Overall survival (OS), with 3.2 years median follow-up, was 60% at 1 year and 48% at 2 years, with projected OS 37% at 5 years. Relapse rates were 29% at 1 year and 33% at 2 years, with relapse mortality of 13% at 1 year, and 20% at 2 years. Nonrelapse mortality (NRM) at 1 year was 27% and 33% at 2 years. 54% of patients developed grade II-IV aGVHD and 67% of patients developed cGVHD within 2 years. On multivariate analysis, HCT-CI score 4 or greater, pre-transplant KPS less than 90, delayed platelet engraftment of more than 15 days, and grade II-IV aGVHD were found to be independent predictors of poor survival. There was no difference in OS or PFS between lymphoid and myeloid malignancies. BuFluTBI is an efficacious NMA regimen, active in both myeloid and lymphoid disease, and is ideally suited for use in patients age 65 and older or with an HCT-CI of 4 or greater.

Phase II Trial of Graft-versus-Host Disease Prophylaxis with Post-Transplantation Cyclophosphamide after Reduced-Intensity Busulfan/Fludarabine Conditioning for Hematological Malignancies.

Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (CY) after ablative HLA-matched bone marrow (BM) transplantation has been reported to have comparable rates of acute GVHD with an apparent reduction in chronic GVHD and infections when compared to historical prophylaxis with a calcineurin-inhibitor (CNI) and methotrexate (MTX). We conducted a phase II trial of post-transplantation CY (post-CY) after reduced-intensity conditioning (RIC) using intravenous busulfan (area under the curve of 4000 micromolar minute), fludarabine (40 mg/m(2)) for 4 days, and CY 50 mg/kg on days +3 and +4 after BM or peripheral blood (PB) transplantations from matched related (MRD) or unrelated donors (MUD). MUD recipients received antithymocyte globulin (ATG); however, a later amendment removed ATG. Forty-nine patients were treated (acute myeloid leukemia/myelodysplastic syndrome, 82%). Median age was 62 years (range, 39 to 72). Fifteen patients received an MRD (9 PB/6 BM); 34 had a MUD (2 PB/32 BM). The cumulative incidence of grade II to IV acute GVHD, III to IV acute GVHD, and chronic GVHD was 58%, 22%, and 18%, respectively. A matched cohort analysis compared outcomes to tacrolimus/methotrexate GVHD prophylaxis and indicated higher rates of acute GVHD grade II to IV (46% versus 19%; hazard ratio [HR], 2.8; P = .02) and treatment-related mortality (HR, 3.3; P = .035) and worse overall survival (HR, 1.9; P = .04) with post-CY. The incidence of chronic GVHD and CMV reactivation did not differ. This study suggests that post-CY should not be used as sole GVHD prophylaxis after a RIC transplantation from HLA-matched donors.

Retrospective review of extra-pulmonary small cell carcinoma and prognostic factors.

BACKGROUND: Extra-pulmonary small cell carcinoma (EPSCC) is a rare cause of malignancy, representing 2.5-5 % of all small cell carcinomas, with an incidence rate of 1000 cases per year in the USA. The purpose of this study is to characterize the location, extent of disease, and survival of patients with EPSCC, and to analyze potential clinical prognostic indicators predicting survival. METHODS: A retrospective review of all patients with EPSCC between the years 2000 and 2010 was conducted. Patients included for analysis had pathologic diagnosis of EPSCC, poorly differentiated tumors, and negative chest imaging at diagnosis. RESULTS: 53 patients were included in the analysis. 23 patients (43 %) had limited disease (LD) at diagnosis, and 30 patients (57 %) had extensive disease (ED) at diagnosis. Carcinoma of unknown primary represented the largest proportion of patients (40 %), followed by genitourinary (26 %), gastrointestinal (15 %), head and neck (11 %), gynecologic (6 %), and breast (2 %). The median overall survival (OS) was 4.7 months; 14.5 months for LD, and 3.7 months for ED. Genitourinary EPSCC had the best median OS at 13.1 months, and GI carcinomas had the worst at 1.7 months. On univariate analysis, ED (p = 0.0001), non-genitourinary EPSCC (p = 0.036), and hyponatremia were associated with worse OS (p = 0.0176). CONCLUSIONS: In a cohort of patients with EPSCC, hyponatremia, non-genitourinary EPSCC, and extensive disease were associated with worse OS. Anatomic site predicted survival, which suggests that pathologic heterogeneity between individual tumor sites, including mixed tumor pathology, may affect the prognosis of this rare disease. Future directions for research should include thorough pathologic and genetic profiles.

Gemcitabine and liposomal doxorubicin (GemDox) for the treatment of relapsed and refractory T-cell lymphomas.

Aggressive T-cell lymphomas (TCL) account for 10-15% of non-Hodgkin lymphomas (NHL) with weaker responses and shorter durations to chemotherapy than other types of NHL. Current therapies for patients with relapsed/refractory Cutaneous T-cell lymphoma (CTCL) have limited efficacy, and short durations of response. Gemcitabine and liposomal doxorubicin have shown single-agent activity in TCL and combined have activity in relapsed B-cell lymphomas. We evaluated outcomes of 18 patients with relapsed/refractory aggressive TCL (13 CTCL, 5 PTCL) treated with a gemcitabine plus liposomal doxorubicin (GemDox) combination and evaluated outcomes with a specific focus on CTCL patients. Significant responses were observed in CTCL patients with an overall response rate of over 80%. In all patients, objective responses were seen in eight patients (50%), with six patients (5 CTCL) able to proceed to allogeneic stem cell transplant. Given limited treatment options for r/r CTCL, GemDox should be considered a therapeutic option in relapsed/refractory CTCL.