Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial.

BACKGROUND: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. METHODS: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. FINDINGS: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. INTERPRETATION: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. FUNDING: AbbVie.

Blinatumomab versus Chemotherapy for Advanced Acute Lymphoblastic Leukemia.

BACKGROUND: Blinatumomab, a bispecific monoclonal antibody construct that enables CD3-positive T cells to recognize and eliminate CD19-positive acute lymphoblastic leukemia (ALL) blasts, was approved for use in patients with relapsed or refractory B-cell precursor ALL on the basis of single-group trials that showed efficacy and manageable toxic effects. METHODS: In this multi-institutional phase 3 trial, we randomly assigned adults with heavily pretreated B-cell precursor ALL, in a 2:1 ratio, to receive either blinatumomab or standard-of-care chemotherapy. The primary end point was overall survival. RESULTS: Of the 405 patients who were randomly assigned to receive blinatumomab (271 patients) or chemotherapy (134 patients), 376 patients received at least one dose. Overall survival was significantly longer in the blinatumomab group than in the chemotherapy group. The median overall survival was 7.7 months in the blinatumomab group and 4.0 months in the chemotherapy group (hazard ratio for death with blinatumomab vs. chemotherapy, 0.71; 95% confidence interval [CI], 0.55 to 0.93; P=0.01). Remission rates within 12 weeks after treatment initiation were significantly higher in the blinatumomab group than in the chemotherapy group, both with respect to complete remission with full hematologic recovery (34% vs. 16%, P<0.001) and with respect to complete remission with full, partial, or incomplete hematologic recovery (44% vs. 25%, P<0.001). Treatment with blinatumomab resulted in a higher rate of event-free survival than that with chemotherapy (6-month estimates, 31% vs. 12%; hazard ratio for an event of relapse after achieving a complete remission with full, partial, or incomplete hematologic recovery, or death, 0.55; 95% CI, 0.43 to 0.71; P<0.001), as well as a longer median duration of remission (7.3 vs. 4.6 months). A total of 24% of the patients in each treatment group underwent allogeneic stem-cell transplantation. Adverse events of grade 3 or higher were reported in 87% of the patients in the blinatumomab group and in 92% of the patients in the chemotherapy group. CONCLUSIONS: Treatment with blinatumomab resulted in significantly longer overall survival than chemotherapy among adult patients with relapsed or refractory B-cell precursor ALL. (Funded by Amgen; TOWER ClinicalTrials.gov number, NCT02013167 .).

Thyroid dysfunctions in adult patients after allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Thyroid dysfunction (TD) is one of the major endocrinopathies shown after allogeneic hematopoietic stem cell transplantation over the long term. The incidence and the risk factors for TD have varied widely. PATIENTS AND METHODS: Two hundred and fifty-nine patients with pre-transplant normal thyroid function tests who survived at least 1 year after allo-HSCT between 2006-2016 were included in the study. RESULTS: Sixty-four patients (25%) developed TD at median of 34 months (range, 1-112 months). Hypothyroidism was detected in 32 patients (12%): 5 patients had primary hypothyroidism, and subclinical hypothyroidism occurred in 27 patients. 18 patients (7%) were diagnosed with hyperthyroidism: 2 patients (0.07%) were treated for primary hyperthyroidism, and 16 patients (6%) were followed for subclinical hyperthyroidism. Euthyroid sick syndrome occurred in 14 cases. None of the patients with thyroid dysfunction developed secondary thyroid malignancy. Receiving high-dose TBI (P = .001) was found to be significant risk for hypothyroidism; older age than median (P = .01) and pre-transplant active disease (P < .0001) were related to hyperthyroidism. CONCLUSIONS: Thyroid dysfunction, mostly hypothyroidism, is a long-term complication after allo-HSCT in 25% of patients. Older age, pre-transplant active disease, and receiving TBI are among the risk factors. Sustained long-term monitoring of thyroid function test should be considered post allo-HSCT.

First pregnancy and live birth in Turkey following frozen-thawed ovarian tissue transplantation in a patient with acute lymphoblastic leukemia who underwent cord blood transplantation.

PURPOSE: To report the first live birth after frozen-thawed ovarian transplantation in Turkey and the second case for an acute lymphoblastic leukemia (ALL) survivor in the world. METHODS: A 19-year-old patient underwent ovarian tissue cryopreservation (OTC) before cord blood transplantation in 2010. She was diagnosed as ALL with a bone marrow biopsy revealing 90% blast ALL-L2 type, and karyotype analyses indicated reciprocal translocation at t(9;22)(q34;q11). The patient received the Berlin-Frankfurt-Munster (BFM) protocol, and complete remission was achieved before fertility preservation. Serum AMH level was measured as 1.5 ng/ml, and 12 antral follicles were counted on ultrasound. She was informed about fertility preservation options and decided to proceed with OTC, with her signed consent before cord blood transplantation in April 2011. Ovarian tissue transplantation (OTT) was performed in 2017 when the patient was menopausal with serum FSH levels > 100 IU/ml and estradiol < 20 pg/ml and hematologically in molecular remission. Detailed molecular analysis, standard histology, and immunohistochemistry demonstrated that the thawed tissue is free of malignant cells. RESULTS: Six months following OTT, she had spontaneous menstruation with serum FSH 11 IU/ml and estradiol 53 pg/ml. Two consecutive IVF cycles yielded three top-quality embryos. Following three embryo transfer cycles, one fresh and two frozen, a healthy term live birth was achieved. Frozen-thawed-transplanted tissues were extracted during caesarean delivery upon the patient's request after a total period of 25 months in vivo, and histopathological evaluation revealed that the tissue was free of leukemic infiltration. CONCLUSION: The authors report the first pregnancy and live birth in Turkey and the second live birth in the world following transplantation of frozen-thawed ovarian tissue in a leukemia survivor. As the transplanted tissues were removed during caesarean delivery, histological findings prove the functionality and the malignant-free status of the transplanted tissue during the grafted period.

HEV seroprevalence in blood donors in Turkey by two commercial total anti-HEV Ab ELISA kits.

Previous hepatitis E virus (HEV) seroprevalence studies in Turkey have shown high variabilities, leading to conflicting results. We aimed to re-evaluate HEV seroprevalence among blood donors in Turkey using the Wantai (Beijing, China) and the Dia.Pro (Milan, Italy) total anti-HEV antibody (Ab) enzyme-linked immunosorbent assay (ELISA) kits and compare their performances and to investigate the presence of HEV RNA in blood donors. Serum total anti-HEV antibodies were determined in a total of 2011 volunteer blood donor samples collected from different regions of Turkey (807 from Ankara, 243 from Kayseri, 284 from Izmir, 200 from Malatya, 200 from Kahramanmaras, and 277 from Van). HEV RNA was evaluated by a real-time polymerase chain reaction in a total of 272 anti-HEV seropositive samples. The country-wide HEV seroprevalence was calculated as 11.5% (Dia.Pro) and 12.2% (Wantai) with seropositivity rates of 12.0%-12.5% in Ankara, 7.4%-8.2% in Kayseri, 14.5%-15.5% in Malatya, 8.1%-8.8% in Izmir, 15.0%-16.0% in Kahramanmaras, and 12.6%-13.4% in Van by Dia.Pro and Wantai kits, respectively. The lowest detectable Ab concentrations were 0.16 and 0.14 units/mL WHO, for the Dia.Pro and the Wantai assays, respectively, showing no significant difference between assays. HEV RNA was not detected in any of the anti-HEV seropositive samples. Compared with previous studies, HEV was shown to have a higher overall seroprevalence in Turkey. Despite its limitation, the current study represents the most comprehensive HEV seroprevalence study in Turkey performed with two different commercial ELISA assays with high sensitivities so far. Further investigation is required to determine HEV genotypes in Turkey.

Subsequent malignancies after allogeneic hematopoietic stem cell transplantation.

We evaluated 979 patients for the development of post-transplant lymphoproliferative disease (PTLD) and solid malignancies after allogeneic hematopoietic stem cell transplantations (allo-HSCT) as a late complication. We found 15 (1.5%) subsequent malignancies; three of these malignancies were PTLD, and twelve were solid tumors. The median time from allo-HSCT to the development of PTLD was 9 (3-20) months and that from allo-HSCT to the development of solid tumors was 93 (6-316) months. The cumulative incidence of evolving subsequent malignancy in patients was 1.3% (±0.5 SE) at 5 years and 3.9% (±1.2 SE) at 10 years. The cumulative incidence of developing subsequent malignancy in patients with benign hematological diseases as the transplant indication was 7.4%±4.2 SE at 5 years. More subsequent malignancy developed in patients having ≥1 year chronic graft-vs-host disease (GVHD; 3.7% in ≥1 year chronic GVHD and 0.7% in <1 year chronic GVHD patient groups, P=.002). Subsequent epithelial tumor risk was higher in ≥1 year chronic GVHD patients than <1 year (3.7% vs 0.1%, P<.001). In multivariate analysis, benign hematological diseases as transplant indication (RR: 5.6, CI 95%: 1.4-22.3, P=.015) and ≥1 year chronic GVHD (RR: 7.1, 95% CI: 2.3-22.5, P=.001) were associated with the development of subsequent malignancy.

Investigation of an algorithm for anti HCV EIA reactivity in blood donor screening in Turkey in the absence of nucleic acid amplification screening.

PURPOSE: In this study we aimed to propose an algorithm for initial anti HCV EIA reactive blood donations in Turkey where nucleic acid amplification tests are not yet obligatory for donor screening. METHODS: A total of 416 anti HCV screening test reactive donor samples collected from 13 blood centers from three cities in Turkey were tested in duplicate by Ortho HCV Ab Version 3.0 and Radim HCV Ab. All the repeat reactive samples were tested by INNO-LIA HCV Ab 3.0 or Chiron RIBA HCV 3.0 and Abbott Real Time HCV. Intra-assay correlations were calculated with Pearson r test. ROC analysis was used to study the relationship between EIA tests and the confirmatory tests. RESULTS: The number of repeat reactive results with Ortho EIA were 221 (53.1%) whereas that of microEIA, 62 (14.9%). Confirmed positivity rate was 14.6% (33/226) by RIBA and 10.6% (24/226) by NAT. Reactive PCR results were predicted with 100% sensitivity and 95% specificity with S/CO levels of 8.1 with Ortho EIA and 3.4 with microEIA. CONCLUSIONS: Repeat reactivity rates declined with a second HCV antibody assay. Samples repeat reactive with one HCV antibody test and negative with the other were all NAT negative. All the NAT reactive samples were RIBA positive. None of the RIBA indeterminate or negative samples were NAT reactive. Considering the threshold values for EIA kits determined by ROC analysis NAT was decided to be performed for the samples above the threshold value and a validated supplemental HCV antibody test for the samples below.

Blood group genotyping in multi-transfused patients.

BACKGROUND: In chronically transfused patients, the classical hemagglutination assays may be inaccurate in defining the RBC phenotypes of the patients due to previous transfusions. DESIGN: DNA samples from 39 multi-transfused patients including thalassemia and sickle cell disease were used for red blood cell genotyping. The Rh-Type and KKD-Type (BAGene, BAG Healthcare) were used to determine the polymorphisms associated with antigen expression for RHD, RHCE and Kell, Kidd, Duffy blood group systems, respectively. Results were compared with previously determined phenotyping results for RhD, RhCcEe and Kell by hemagglutination method. RESULTS: Nineteen out of the 37(51%) patients had discrepancies between genotyping and phenotyping results in a total of 25 alleles. In 12 patients, the discrepancies had the potential of alloimmunization. CONCLUSION: Blood group genotyping has vital importance in transfusion management of chronically transfused patients especially if the patients were not phenotyped before starting the initial transfusions.

Outcomes of Autologous Stem Cell Transplantation as a Consolidative Strategy for the Treatment of Primary and Isolated Secondary Central Nervous System Diffuse Large B Cell Lymphomas.

INTRODUCTION: Standard consolidation for primary diffuse large B cell lymphoma (DLBCL) of the central nervous system (CNS) (PCNSL) is not established. This single center, retrospective observational study aims to define the outcomes of consolidative high dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) in patients with PCNSL and isolated secondary CNS DLBCL (SCNSL) and evaluate the prognostic factors. PATIENTS AND METHODS: All consecutive patients performed an HDC/ASCT for PCNSL or isolated SCNSLs between October 2012 and February 2022 were identified. Primary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: Among 35 patients included, 28 had PCNSL and 7 had isolated SCNSL. Median age was 51 (16-78). Males constituted 48.6%. Median follow-up after HDC/ASCT was 42.0 months. MATRIX (51.4%) and TEAM (80.0%) were the most frequent regimens of induction and conditioning, respectively. OS and PFS 1- and 2-year after HDC/ASCT were 68.0%, 57.0%, 58.0%, 48.0%, respectively. Increasing age, poor performance and comorbidities were associated with lower OS and PFS and higher non-relapse mortality (NRM). Complete response (CR) 1 at HDC/ACST was independently associated with higher OS and PFS [hazard ratio (HR): 4.67 and 6.99, respectively]. CONCLUSION: In patients < 60 years consolidative HDC/ASCT yields promising OS and PFS. Patients ≥ 60 years may less likely benefit from consolidative HDC/ASCT and should be studied further in trials of novel agents, lower doses of consolidative radiotherapy and dose-adjusted conditioning regimens. Not only age, but also comorbidities, clinical performance and response to induction correlate with outcomes. Patients with isolated SCNSL may achieve similar outcomes.

Eltrombopag for the Treatment of Poor Graft Function Following Haematopoietic Cell Transplantation: Real-Life Data

Background: Eltrombopag has an off-label indication for haematopoietic cell transplantation in patients experiencing delayed thrombocyte recovery and/or thrombocytopaenia. Aims: To present our centre's experience of using this agent not only for post- haematopoietic cell transplantation thrombocytopaenia but also for poor graft functioning in the post-haematopoietic cell transplantation setting. Study Design: Retrospective cross-sectional study. Methods: Thirty-nine patients who had persistent cytopaenia following haematopoietic cell transplantation and treated with eltrombopag at our centre between October 2011 and December 2021 were retrospectively identified. During this period, 9 (23.1%) and 30 (76.9%) patients who underwent allogeneic transplantations, respectively, received eltrombopag. Results: The female-to-male ratio was 12:27, and the median transplant age was 49 (18-70) years. Eight (20.5%) patients had isolated thrombocytopaenia, 19 (49.4%) had bi-lineage cytopaenia and 12 (30.1%) had pancytopaenia. Patients received a median of 50 mg/day (25-150 mg/day) of eltrombopagfor a median duration of 82 (24-386) days. Nine (23.1%) patients had autologous haematopoietic cell transplantation, and 30 (76.9%) had allogeneic haematopoietic cell transplantation (14 unrelated, 9 sibling and 7 haploidentical). The median donor age was 32 (20-67) years. The median follow-up was 16.4 (1.8-84.3) months. The median pre-treatment platelet count was 11x109/l (1-23), which increased to 41x109/l (6-150). The median platelet count increment was 29.5x109/l (p = 0.001). The pre-treatment median neutrophil count was 1.19x109/l (0.39-5.1), which increased to 2.35 x109/l (0.1-5.33) (p = 0.05), and the pre-treatment median haemoglobin was 8.3 (6.2-14) g/dl, which increased to 10 (6.2-14) g/dl (p = 0.001) with eltrombopag. No eltrombopag-related hepatotoxicity occurred; however, 1 (2.6%) patient failed to continue treatment because of two consecutive episodes of deep venous thrombosis. Six (15.4%) patients were unresponsive to eltrombopag and dependent on blood product transfusions. After a median time of 82 days, 61.5% of the patients discontinued eltrombopag successfully. Conclusion: The results confirmed that eltrombopag could provide a rapid, sustained response in patients with poor graft functioning after haematopoietic cell transplantation. This finding is essential given the high rate of non-relapse mortality caused by poor graft functioning after haematopoietic cell transplantation.

Allogeneic Hematopoietic Stem Cell Transplantation for Primary Myelofibrosis: A 20-year Experience in a Single Center

Background: Allogeneic hematopoietic stem cell transplantation is a well-established approach for patients diagnosed with primary myelofibrosis and remains the only potentially curative treatment. Aims: To present the overall outcome of patients with myelofibrosis treated with allogeneic hematopoietic stem cell transplantation. Study Design: A retrospective cross-sectional study. Methods: This study is a retrospective analysis of 26 consecutive patients with primary myelofibrosis who underwent transplantation at our center between January 2002 and January 2022. Disease and transplant variables contributing to outcomes were analyzed. Results: The median age at the time of transplantation was 52.5 (range, 32-63) years and the median time from diagnosis to allogeneic hematopoietic stem cell transplantation was 25 (range, 3.1-156.8) months. Myeloablative conditioning and reduced-intensity conditioning regimens were used in 8 (30.8%) and 18 (69.2%) transplantations, respectively. Neutrophil and platelet engraftment was achieved in 23 patients at a median follow-up of 21.2 months (range, 12 days to 234.8 months). Primary graft failure occurred in 1 of 23 patients (4.3%). Neutrophil and platelet engraftment occurred at a median of 16 (range, 12-39) days and 20 (range, 11-78) days, respectively. Acute graft-versus-host disease was seen in 11 of 22 patients engrafted allografts, of which 7 (31.8%) were grade 3-4 acute graft-versus-host disease. Eight patients (36.4%) developed chronic graft-versus-host disease, and three cases were extensive. Four patients (19%) relapsed after a median of 5.5 months, and three patients received donor lymphocyte infusion. The 3-year overall survival rate of the entire study population was 46.2%. The median overall survival was not reached in the myeloablative conditioning group; however, it was 11.9 months in the reduced-intensity conditioning group (p =0.3). According to the donor graft source, the median overall survival was 0.73 months in mismatched unrelated graft recipients, 12 months in matched sibling donors, and not reached in matched unrelated graft recipients (p = 0.03). The 3-year progression-free survival rate of patients who survived > 100 days was 74.7%. The effect of JAK-2 status, graft source, conditioning regimen or dynamic international prognostic scoring system on progression-free survival was not statistically significant. Conclusion: Given the poor prognosis of non-transplant recipients and the lack of non-transplant curative approaches, our results support the consideration of allogeneic hematopoietic stem cell transplantation for eligible patients with primary myelofibrosis.

Case-matched comparison with standard versus reduced intensity conditioning regimen in chronic myeloid leukemia patients.

This retrospective case-matched study evaluated the efficacy of reduced intensity conditioning (RIC) regimen on early and late allogeneic transplant outcome in chronic myeloid leukemia (CML) patients. Twenty-eight patients conditioned with RIC regimen were matched to 56 patients who received a myeloablative conditioning (MAC) regimen. The main criteria for case matching among our CML allotransplant cohort were the Gratwohl scoring system. The median score was 2 (1-4) in each group. The pretransplant disease status was first chronic phase (CP1, n = 20), CP2 (n = 2), and advanced phase (n = 6) in RIC, and CP1 (n = 46), CP2 (n = 3), and advanced phase (n = 7) in MAC. The duration of neutropenia and thrombocytopenia was shorter in RIC than MAC. The grade and duration of mucositis were less in RIC. The need for total parenteral nutrition (21% vs. 77%, p < 0.0001) and febrile neutropenic episodes (50% vs. 95%, p < 0.0001) were observed less frequently in RIC compared with MAC-given patients. Acute or chronic graft versus host diseases (GvHD) were not affected by the intensity of conditioning regimen. The incidence of transplant-related mortality was higher in MAC (7% vs. 14%, p = 0.01). Although more relapse/progression was observed in the RIC group, the probability of 5- and 10-year leukemia-free- and overall survival were similar regardless of conditioning regimen intensity (p > 0.05). In early first CP, the pair of female donor-male recipient and the development of chronic GvHD prolonged both leukemia-free survival and overall survival in multivariate analysis. According to our single-center matched-pair analysis, the use of RIC regimens in patients with low-risk CML results with toxicities less, responses later, and relapses more frequent than the MAC regimens.

How Does Influenza A (H1N1) Infection Proceed in Allogeneic Stem Cell Transplantation Recipients?

The clinical course of influenza A (H1N1) infection in allogeneic hematopoietic stem cell transplantation (AHSCT)recipients is not clearly known. We report 3 AHSCT recipients that were infected with influenza A (H1N1). Each of thepatients had a different hematological disease and was at a different post-transplantation stages. All the patients weretreated with oseltamivir, and zanamivir was switched to oseltamivir in 1 patient. All the patients survived without anycomplications. The course of swine flu can vary and progress with bacterial or other viral infections in immunosuppressedpatients.

Gemcitabine, Cisplatin, and Dexamethasone as a Salvage and Mobilization Chemotherapy Before Autologous Stem Cell Transplantation is Effective and Safe Outpatient Regimen in Relapsed and Refractory Hodgkin Lymphoma Patients.

BACKGROUND: Second line salvage chemotherapy followed by autologous stem cell transplantation (ASCT) is the current standard treatment for eligible patients with relapsed and refractory (R/R) Hodgkin lymphoma (HL). Several salvage regimens have been used before ASCT. However the optimal salvage regimen is still unclear. We report outcome of patients with R/R HL treated with gemcitabine, cisplatin, and dexamethasone (GDP) regimen before ASCT in this retrospective study aiming at evaluating efficacy, stem cell mobilization activity and safety of GDP in a real-life setting. PATIENTS AND METHODS: Forty-five patients with R/R HL who were treated with GDP as salvage and mobilization regimen before ASCT were analyzed retrospectively. Peripheral blood stem cells (PBSC) were collected after GDP. All patients underwent ASCT after 2 cycles of GDP. RESULTS: Thirty-six (80%) patients achieved overall response including 24 (53.3%) complete response (CR). PBSC collections were adequate in all patients with a median number of 11.01 × 106/kg CD34+ cells. The most common grade 3/4 hematological adverse events were thrombocytopenia (31.1%) and neutropenia (22.2%). There were no febrile neutropenic episodes. Grade 3 or 4 renal, hepatic, or cardiac toxicity was not observed. The 4 year progression-free survival and overall survival for patients receiving GDP followed by ASCT were 72% and 92%, respectively. CONCLUSION: Our results suggest that GDP is a viable therapeutic option before ASCT with high response rate, favorable toxicity profile and excellent mobilization potential. Applicability of GDP on an outpatient setting also provides advantage over other effective salvage regimens.

Alpha-1-Antitrypsin Experience for Steroid-Resistant Acute Graft-Versus-Host Disease.

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) treatment has a low response rate and a high risk of infection in allogeneic hematopoietic stem cell transplantation. The standard approach to be applied in this situation is uncertain. This study aims to evaluate the effectiveness and safety of alpha-1-antitrypsin (AAT). In the study, the results of five SR-aGVHD patients received AAT evaluated. Complete response was seen 2 of four patients with gastrointestinal (GI) aGVHD, partial response in one GI and one liver aGVHD. The overall response rate was 80%. AAT is an effective and safe treatment option in SR-aGVHD.

Pretransplant Consolidation Therapies Improve the Outcome of Myeloablative Allogeneic Transplantation in Adults with Ph-negative Acute Lymphoblastic Leukemia.

BACKROUND AND AIM: The benefit of pre-transplant consolidation in patients with acute lymphoblastic leukemia (ALL) who achieved first complete remission (CR1) has not yet been clearly demonstrated. Here, we aimed to investigate the relationship between the treatments received before transplantation and transplant outcome in Ph-ALL patients who underwent myeloablative allo-HSCT in CR1. PATIENTS AND METHODS: A total of 55, 32 (58.2%) men and 23 (41.8%) women, who underwent allo-HSCT with the diagnosis of Ph-ALL were evaluated retrospectively. All patients underwent to allo-HSCT with myeloablative conditioning regimen in the 1st CR from the available donor. RESULTS: In patients who received >2 consolidation, the 2-year and 3-year OS was 69% and 65%, respectively, while the 2-year and 3-year OS was 39% and 26%, respectively, in those who received < 2 consolidation (P =.03). RFS was similar in both groups (P = .8). One year- NRM was found 28% in patients who received ≥ 2 consolidations, and 37% in patients who received <2 consolidation (P =.06). L-asparaginase, high dose methotrexate, and cranial treatments given before transplantation had no effect on transplant outcomes (P > .05). CONCLUSION: Contrary to the belief that pre-transplant consolidation is not beneficial in ALL patients who proceed with allo-HCST in CR1, our results showed that consolidation treatments reduce NRM and improve the survival.

Characterization of hepatitis B virus in Turkish blood donors, and the prevalence of the SP1 splice variant.

Hepatitis B is a disease of the liver that can manifest acutely, or persist chronically as a result of infection with the hepatitis B virus (HBV). Turkey has a moderate endemicity level of HBV infection, and all data published to date has shown this to be of genotype D, predominantly of subgenotype D1. However the sequences of very few full genomes have been published. The aim of this study was to characterize the molecular profile of hepatitis B virus in asymptomatic, first-time Turkish blood donors. The results confirm that genotype D, subgenotype D1 is the most prevalent HBV strain in Turkey, accounting for 94% of cases. Subgenotypes D2 and D3 were present as minority strains (4% and 2%, respectively). A singly spliced HBV variant that is capable of forming defective HBV particles and has been associated with apoptosis and activation of T-cell responses was also detected in 52.5% of samples screened, co-circulating with wild type genomes.

Highlighting the Prognostic Importance of Measurable Residual Disease Among Acute Myeloid Leukemia Risk Factors

Objective: The optimal timing of measurable residual disease (MRD) evaluation in acute myeloid leukemia (AML) patients has not been well defined yet. We aimed to investigate the impact of MRD in pre- and post-allogeneic hematopoietic stem cell transplantation (AHSCT) periods on prognostic parameters. Materials and Methods: Seventy-seven AML patients who underwent AHSCT in complete morphological remission were included. MRD analyses were performed by 10-color MFC and 10-4 was defined as positive. Relapse risk and survival outcomes were assessed based on pre- and post-AHSCT MRD positivity. Results: The median age of the patients was 46 (range: 18-71) years, and 41 (53.2%) were male while 36 (46.8%) were female. The median follow-up after AHSCT was 12.2 months (range: 0.2-73.0). The 2-year overall survival (OS) in the entire cohort was 37.0%, with a significant difference between patients who were MRD-negative and MRD-positive before AHSCT, estimated as 63.0% versus 16.0%, respectively (p=0.005). MRD positivity at +28 days after AHSCT was also associated with significantly inferior 2-year OS when compared to MRD negativity (p=0.03). The risk of relapse at 1 year was 2.4 times higher (95% confidence interval: 1.1-5.6; p=0.04) in the pre-AHSCT MRD-positive group when compared to the MRD-negative group regardless of other transplant-related factors, including pre-AHSCT disease status (i.e., complete remission 1 and 2). Event-free survival (EFS) was significantly shorter in patients who were pre-AHSCT MRD-positive (p=0.016). Post-AHSCT MRD positivity was also related to an increased relapse risk. OS and EFS were significantly inferior among MRD-positive patients at +28 days after AHSCT (p=0.03 and p=0.019). Conclusion: Our results indicate the importance of MRD before and after AHSCT independently of other factors.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in acute myeloblastic leukemia (AML): A single center experience.

OBJECTIVE: We retrospectively analyzed the impact of pre- and post-transplant variables on the outcome of transplanta¬tion in 145 consecutive patients with acute myeloblastic leukemia (AML) allografted from their HLA-identical siblings in our single center cohort. RESULTS: The stem cell source used was bone marrow (BM) (36.6%) or peripheral blood (PB) (63.4%). Both neutrophil and platelet engraftments were observed on the median 14th day. Engraftment was faster in the PB group than in the BM group (p<0.0001). Severe acute graft versus host disease (aGvHD) was observed in 27.9% of the patients while chronic (c)GvHD developed in 61.2%. The use of PB was associated with more severe aGvHD. Estimated leukemia-free survival (LFS) and overall survival (OS) at 10 years were 43.4%±5.2% and 52.7%±4.6%, respectively. CONCLUSION: Both in univariate and multivariate analyses for LFS and OS, remission status at transplant and the presence of aGvHD were independent risk factors.

Incomplete Antibodies May Reduce ABO Cross-Match Incompatibility: A Pilot Study.

OBJECTIVE: Any erythrocyte transfusion among humans having type A or B blood groups is impossible due to antibodies causing fatal transfusion complications. A cross-match test is performed to prevent immune transfusion complications before transfusion. Our hypothesis is that the fragment antibody (Fab) part of the antibody (incomplete antibody) may be used to prevent an immune stimulus related to the complete antibody. Therefore, we designed a pilot study to evaluate the effectiveness of these incomplete antibodies using cross-match tests. MATERIALS AND METHODS: Pepsin enzyme and staphylococcal protein A columns were used to cut anti-A and anti-B monoclonal antibodies and purify their Fab (2) fragments, respectively. An Rh-positive erythrocyte suspension with purified anti-A Fab (2) solution and B Rh-positive erythrocyte suspension with purified anti-B Fab (2) solution were combined correspondingly. Cross-match tests were performed by tube and gel centrifugation methods. The agglutination levels due to the anti-A and anti-B Fab (2) antibodies and their effects on the agglutination normally observed with complete antibodies were then measured. RESULTS: No agglutination for the purified incomplete anti-A Fab (2) with A Rh+ erythrocyte and anti-B Fab (2) with B Rh+ erythrocyte combinations was observed in the tube cross-match tests. These agglutination levels were 1+ in two wells in the gel centrifugation cross-match tests. Fab (2)-treated erythrocytes were also resistant to the agglutination that normally occurs with complete antibodies. CONCLUSION: We determined that the Fab (2) fragments of antibodies may not only be used to obtain a mild or negative reaction when compared to complete antibodies, but they might also be used for decreasing ABO incompatibility. Incomplete antibodies might be a therapeutic option in autoimmune hemolytic anemia and they may also be used in solid organ or hematopoietic stem cell transplantation. Therefore, we have planned an in vivo study to prove these in vitro findings.