Nonacog Alfa for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients with Moderately Severe or Severe Hemophilia B in India.

Purpose: Hemophilia B is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor IX (FIX) clotting activity. This study evaluated safety and efficacy of nonacog alfa, a recombinant human blood coagulation FIX replacement product, in males aged 12-65 years with hemophilia B (FIX activity ≤ 2%) with or without inhibitors in India. Methods: In this multicenter, open-label, post-approval phase 4 study, participants were treated for up to 8 weeks, with up to a 4-week screening period and a subsequent post-treatment 28-day safety observation period. Intravenous nonacog alfa 40 IU/kg (range 13-78 IU/kg) was administered at intervals of 3-4 days, in accordance with the approved local product document. Results: A total of 25 participants were enrolled and completed the study. No participants developed FIX inhibitors during the study, experienced treatment-related adverse events (AEs) or serious AEs, or developed a thrombotic event and/or hypersensitivity reaction. No participants experienced bleeding events requiring on-demand treatment with nonacog alfa. Seventeen bleeding episodes (16 spontaneous and 1 traumatic) were reported in 10 participants; all occurred post treatment, with the exception of a minor gum-bleeding event, and were managed without treatment. The mean (SD) annualized total factor consumption (TFC) per patient was 224,582 (75,527) IU; the mean (SD) annualized TFC by weight per patient was 3639 (573) IU/kg. Conclusion: Nonacog alfa was safe and effective for the prevention of hemorrhagic episodes in Indian males with congenital, severe hemophilia B. No participants developed FIX inhibitors, and no new safety signals were reported.

Correction to: Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

[This corrects the article DOI: 10.1007/s12288-022-01602-5.].

Efficacy and Safety of Biosimilar Romiplostim Versus Innovator Romiplostim in Patients with Chronic Immune Thrombocytopenia.

Romiplostim is a Food and Drug Administration (FDA)-approved therapy for immune thrombocytopenia (ITP). Biosimilar is a biological product that has no clinical meaningful difference from an existing FDA-approved reference product. It has a potential of lowering health-care-related cost. Biosimilar of romiplostim can be made available to patients with ITP at a low cost and can be beneficial in providing the best therapy. Thus, the efficacy and safety of biosimilar romiplostim (ENZ110) was compared with innovator romiplostim (Nplate) with respect to platelet response in patients with chronic ITP. This was a prospective, multicenter, randomized, and double-blind clinical trial. Patients with chronic ITP, aged 18-65 years, were enrolled in a study and were randomized to receive either ENZ110 or Nplate in a 3:1 ratio for a treatment period of 12 weeks, respectively. After completion of the treatment period, the patients were followed-up for one week to evaluate the platelet response and to monitor the adverse events (AEs). Over the duration of 12 weeks, platelet response of > 50 × 109/L was achieved in 85.3% patients treated with ENZ110 and in 75.0% patients treated with Nplate in per protocol population. In intent-to-treat population, 83.8% patients with ENZ110 and 76.9% patients with Nplate achieved a platelet response of > 50 × 109/L. In the ENZ110 group, 111 AEs were recorded in 66.7% patients, while 18 AEs were reported in 61.5% patients in the Nplate group. The study demonstrated non-inferiority with comparable efficacy and safety between biosimilar romiplostim and innovator romiplostim in patients with chronic ITP. Trial registration number and date of registration: CTRI/2019/04/018614.

Moroctocog Alfa (AF-CC) for Prophylaxis and Treatment of Bleeding Episodes in Previously Treated Patients with Hemophilia A in India.

Purpose: Hemophilia A is an X-linked congenital disorder, characterized by factor VIII (FVIII) deficiency. Globally, India has the highest population of patients with hemophilia, and there is a clear unmet need for appropriate and effective treatment for this patient population. This multicenter, open-label, post-approval study evaluated the safety and efficacy of moroctocog alfa in patients with moderate or severe congenital hemophilia A in India. Methods: Intravenous moroctocog alfa was administered 30 ± 5 IU/kg 3 times weekly for bleeding prophylaxis, according to the local product document. Participants were treated for up to 8 weeks, with an up to 4-week screening period and a subsequent post-treatment, 28-day safety observation period. Patients continued in the study until at least 24 exposure days or a period of up to 8 weeks on moroctocog alfa. Results: A total of 50 participants were enrolled, and 48 (85.7%) completed the study. No participants developed FVIII inhibitors during the study. The mean (SD) annualized bleeding rate during moroctocog alfa prophylaxis was 0.79 (2.0) with a median (range) of 0.00 (0.0, 6.8). The mean (SD) annualized total factor consumption (TFC) per participant was 287,432 (93,866) IU; the mean (SD) annualized TFC by weight per participant was 4176 (858) IU/kg. Moroctocog alfa was well tolerated with no reported treatment-emergent adverse event-related dose reductions, discontinuations, or serious adverse events. Conclusion: Moroctocog alfa was safe, effective, and well tolerated in Indian participants with congenital moderate to severe hemophilia A. No participant developed FVIII inhibitors during the study.

Managing invasive procedures in haemophilia patients with limited resources, extended half-life concentrates or non-replacement therapies in 2022.

New treatment possibilities and modalities are now available globally for patients with haemophilia requiring surgery or invasive procedures. The first is the appropriate application of low-dose protocols of clotting factor concentrates (CFC) achieving adequate perioperative haemostasis in resources constraint environments. The increasing availability of CFC through humanitarian aid programs allows more invasive surgeries to be performed for which efficacy and safety data should be more widely collected and reported. Second, extended half-life CFC that are increasingly available in many countries represent valuable alternatives to standard half-life products in surgical patients allowing reduced number of infusions and lower consumption, in particular for extended half-life factor IX. Third, in the era of recently introduced nonfactor prophylaxis, some minor surgical procedures can now be performed without additional haemostatic treatment, others with few low-dose administrations of CFC or bypassing agents. Additional factor VIII/IX or recombinant activated factor VII has proven to be safe and effective in association with emicizumab for major surgeries and it was effectively given at low doses in association with fitusiran (including activated prothrombin complex concentrate). No thrombotic complications have been reported in the surgical setting so far. A multidisciplinary team/facility remains crucial to manage major surgery in patients on prophylaxis with these new agents.

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature.

INTRODUCTION: von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF. AIM: To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD METHODS: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed', to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed. RESULTS: The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease. In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6-12 m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma-associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies. Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab. CONCLUSION: In conclusion, this review supports the safety and efficacy of emicizumab in type 3 VWD patients with or without alloantibodies. Further large studies are required to confirm the safety and efficacy of emicizumab in VWD.

Patient blood management in India - Review of current practices and feasibility of applying appropriate standard of care guidelines. A position paper by an interdisciplinary expert group.

In a developing country like India, with limited resources and access to healthcare facilities, dealing with massive hemorrhage is a major challenge. This challenge gets compounded by pre-existing anemia, hemostatic disorders, and logistic issues of timely transfer of such patients from peripheral hospitals to centers with adequate resources and management expertise. Despite the awareness amongst healthcare providers regarding management modalities of bleeding patients, no uniform Patient Blood Management (PBM) or perioperative bleeding management protocols have been implemented in India, yet. In light of this, an interdisciplinary expert group came together, comprising of experts working in transfusion medicine, hematology, obstetrics, anesthesiology and intensive care, to review current practices in management of bleeding in Indian healthcare institutions and evaluating the feasibility of implementing uniform PBM guidelines. The specific intent was to perform a gap analysis between the ideal and the current status in terms of practices and resources. The expert group identified interdisciplinary education in PBM and bleeding management, bleeding history, viscoelastic and platelet function testing, and the implementation of validated, setting-specific bleeding management protocols (algorithms) as important tools in PBM and perioperative bleeding management. Here, trauma, major surgery, postpartum hemorrhage, cardiac and liver surgery are the most common clinical settings associated with massive blood loss. Accordingly, PBM should be implemented as a multidisciplinary and practically applicable concept in India in a timely manner in order to optimize the use the precious resource blood and to increase patients' safety.

Invasive procedures in patients with haemophilia: Review of low-dose protocols and experience with extended half-life FVIII and FIX concentrates and non-replacement therapies.

The performance of surgery and invasive procedures in patients with haemophilia is currently facing new challenges globally. The first is the appropriate application of low-dose protocols of clotting factor concentrates (CFC) achieving adequate perioperative haemostasis in resource constraint environments. The increasing availability of CFC through humanitarian aid programmes allows more invasive surgeries to be performed for which efficacy and safety data should be more widely collected and reported. Second, extended half-life CFC that are increasingly available in many countries represent valuable alternatives to standard half-life products in surgical patients allowing reduced number of infusions and lower consumption, in particular for extended half-life factor IX. Third, in the era of recently introduced non-factor prophylaxis, some minor surgical procedures can now be performed without additional haemostatic treatment, others with few low-dose administrations of CFC or bypassing agents. Additional factor VIII or bypassing treatment has proven to be safe and effective in association with emicizumab for major surgeries, and it was effectively given at low doses in association with fitusiran. No thrombotic complications have been reported in the surgical setting so far. A multidisciplinary team/facility remains crucial to manage major surgery in patients on prophylaxis with these new agents.

Turoctocog alfa is safe for the treatment of Indian patients with hemophilia A: Guardian 10 trial results.

BACKGROUND: Hemophilia A is an X chromosome-linked bleeding disorder caused by the deficiency of coagulation factor VIII (FVIII). The majority of the Indian population with hemophilia A use plasma-derived clotting factors and, in some instances, fresh frozen plasma and cryoprecipitate. Safer and more efficient treatment options are needed for this group of patients. OBJECTIVES: To assess the safety of turoctocog alfa, a third-generation recombinant FVIII molecule, for the treatment and prophylaxis of bleeding episodes in previously treated Indian patients with moderate or severe hemophilia A. PATIENTS/METHODS: This single-country, multicenter, open-label, nonrandomized trial enrolled 60 patients who received prophylactic treatment with turoctocog alfa for 8 weeks, which corresponded to a minimum of 20 exposure days. Confirmed development of FVIII inhibitors during the 8-week treatment period was evaluated. Other assessments included frequencies of adverse drug reactions (ARs), serious adverse reactions, drug-related allergic reactions, and infusion reactions during the 12-week period after the first treatment; hemostatic effect of turoctocog alfa for the treatment of bleeding episodes; and total annualized dose of turoctocog alfa administered during the 8-week treatment period. RESULTS: No incidence of FVIII inhibitors was detected. No safety concerns such as ARs, serious ARs, or drug-related allergic reactions were noted. The hemostatic success rate for the treatment of bleeding episodes with turoctocog alfa was 81.6%. CONCLUSIONS: The trial results demonstrated that turoctocog alfa is a safe treatment option for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with hemophilia A in the Indian population.

Correlation of Day 8 Steroid Response with Bone Marrow Status Measured on Days 14 and 35, in Patients with Acute Lymphoblastic Leukemia Being Treated with BFM Protocol.

Berlin-Frankfurt-Munster (BFM) protocol is commonly used in India for treatment of acute lymphoblastic leukemia (ALL). The present study was conducted to correlate day 8 steroid response with bone marrow status (by morphology and flow cytometry) at day 14 and day 35 of treatment. It was a prospective study which included all newly diagnosed ALL patients who visited hospital between March 2013 and February 2015 i.e. 2 years. On 8th day, the number of lymphoblasts was counted in the peripheral blood. Based on the number of blasts patients were classified as good steroid responders and poor steroid responders. Following pre-induction steroids patients were given induction therapy. During this phase on day 14 and day 35 bone marrow (BM) aspiration study was done. Later day 8 steroid response, Day 14 BM status and day 35 BM status were correlated. Results showed that there was a statistically significant correlation between day 8 steroid response and day 14 BM status (both by morphology and flow cytometry). There was no statistically significant correlation between day 8 steroid response and day 35 BM status (both by morphology and flow cytometry). There was no statistically significant correlation between day 14 and day 35 BM status (both by morphology and flow cytometry). Sensitivity and specificity of morphological evaluation of BM was much lower compared to minimal residual disease assessment by flow cytometry. There is a need to incorporate flow cytometry in risk stratification of patients who are being treated with BFM 2002 protocol.

Prevalence of FVIII inhibitors in severe haemophilia A patients: Effect of treatment and genetic factors in an Indian population.

INTRODUCTION: Factor replacement therapy in treatment of haemophilia A is complicated by the production of neutralising antibodies known as inhibitors. The formation of inhibitors is multifactorial being associated with both genetic and environmental factors. AIM: To document the prevalence of inhibitors in severe haemophilia in the community where most patients receive only infrequent episodic replacement therapy and evaluate the factors which could be contributing to it. METHODS: Community based camps were conducted in different parts of the country. Patients were assessed through a structured questionnaire and blood samples were obtained for laboratory evaluation of inhibitors and defined immunological parameters. RESULTS: Inhibitors were present in 87/447 (19.5%) of the evaluated patients. High-titre inhibitor (>5 Bethesda Units [BU]) was identified in 31 (35.6%) patients. HLA DRB1-13-positive cases (RR = 2.04; 95% CI 1.06-3.911; P = 0.033) had an increased risk of inhibitor formation which was retained in the high-titre subset. A decreased risk of inhibitor formation was noted with heterozygous IL4-590 C/T allele (RR = 0.22; 95% CI 0.108-0.442: P = 0.000). There were no significant correlations between any of the evaluated environmental factors and the development of inhibitors in this study. CONCLUSION: The overall prevalence of inhibitors in patients with severe haemophilia A is similar to that reported among patients receiving regular replacement therapy. The data from this study, limited by its retrospective and cross-sectional study design, would suggest that genetic rather than environmental are more likely to impact the development of inhibitors.

Safety and efficacy of intravenous immunoglobulin (Flebogamma® 10% DIF) in patients with immune thrombocytopenic purpura.

AIM: To evaluate the safety and efficacy of 10% intravenous immunoglobulin (IVIG; Flebogamma® 10% DIF) in individuals with chronic immune thrombocytopenic purpura (ITP). PATIENTS & METHODS: Patients aged 3-70 years, diagnosed with chronic ITP, received 1 g/kg IVIG over two consecutive days. RESULTS: 64 evaluable patients (51 adults, 13 children) with chronic ITP received IVIG. The primary efficacy end point (increased platelet counts from ≤20 × 109/l to ≥50 × 109/l by day 8) was achieved by 81.3% of patients; mean time to response was 1.7 days (all responders). Adverse events, mostly mild or moderate, were reported in 59 patients (92.2%). CONCLUSION: Flebogamma® 10% DIF administered over two consecutive days was safe and effective in adults and children with chronic ITP.

Safety and efficacy of a 10% intravenous immunoglobulin preparation in patients with immune thrombocytopenic purpura: results of two international, multicenter studies.

AIM: To assess safety and efficacy of a 10% intravenous immunoglobulin in patients with primary immune thrombocytopenic purpura (ITP). PATIENTS & METHODS: ITP patients in two multicenter studies (Trials A/B) were treated with 2 g/kg Flebogamma® 10% DIF (over 2-5 days) and were followed up to 1-3 months. RESULTS: 18 patients in Trial A and 58 in Trial B were enrolled (12 children in Trial B). The response rate (platelet count ≥50 × 109/l) was 72.2% (Trial A) and 76.1/100% (adults/children; Trial B). Most patients improved bleedings (83.3% Trial A; 88.9% Trial B). Potential treatment-related adverse events were reported by 38.9% (Trial A) and 30.4/83.3% (adults/children; Trial B) of patients. All serious adverse events (five patients) resolved without sequelae. CONCLUSION: Flebogamma 10% DIF was effective and safe in patients with primary ITP.

A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A.

BACKGROUND: The development of neutralizing anti-factor VIII alloantibodies (inhibitors) in patients with severe hemophilia A may depend on the concentrate used for replacement therapy. METHODS: We conducted a randomized trial to assess the incidence of factor VIII inhibitors among patients treated with plasma-derived factor VIII containing von Willebrand factor or recombinant factor VIII. Patients who met the eligibility criteria (male sex, age <6 years, severe hemophilia A, and no previous treatment with any factor VIII concentrate or only minimal treatment with blood components) were included from 42 sites. RESULTS: Of 303 patients screened, 264 underwent randomization and 251 were analyzed. Inhibitors developed in 76 patients, 50 of whom had high-titer inhibitors (≥5 Bethesda units). Inhibitors developed in 29 of the 125 patients treated with plasma-derived factor VIII (20 patients had high-titer inhibitors) and in 47 of the 126 patients treated with recombinant factor VIII (30 patients had high-titer inhibitors). The cumulative incidence of all inhibitors was 26.8% (95% confidence interval [CI], 18.4 to 35.2) with plasma-derived factor VIII and 44.5% (95% CI, 34.7 to 54.3) with recombinant factor VIII; the cumulative incidence of high-titer inhibitors was 18.6% (95% CI, 11.2 to 26.0) and 28.4% (95% CI, 19.6 to 37.2), respectively. In Cox regression models for the primary end point of all inhibitors, recombinant factor VIII was associated with an 87% higher incidence than plasma-derived factor VIII (hazard ratio, 1.87; 95% CI, 1.17 to 2.96). This association did not change in multivariable analysis. For high-titer inhibitors, the hazard ratio was 1.69 (95% CI, 0.96 to 2.98). When the analysis was restricted to recombinant factor VIII products other than second-generation full-length recombinant factor VIII, effect estimates remained similar for all inhibitors (hazard ratio, 1.98; 95% CI, 0.99 to 3.97) and high-titer inhibitors (hazard ratio, 2.59; 95% CI, 1.11 to 6.00). CONCLUSIONS: Patients treated with plasma-derived factor VIII containing von Willebrand factor had a lower incidence of inhibitors than those treated with recombinant factor VIII. (Funded by the Angelo Bianchi Bonomi Foundation and others; ClinicalTrials.gov number, NCT01064284; EudraCT number, 2009-011186-88.).

Long-acting recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management of subjects with haemophilia B in the phase 3 B-LONG study.

In the phase 3 B-LONG (Recombinant Factor IX Fc Fusion Protein [rFIXFc] in Subjects With Haemophilia B) study, rFIXFc demonstrated a prolonged half-life compared with recombinant factor IX (rFIX), and safety and efficacy for prophylaxis and treatment of bleeding in subjects with moderately-severe to severe haemophilia B. In this B-LONG sub-analysis, rFIXFc was evaluated for efficacy in subjects requiring major surgery. Dosing was investigator-determined. Assessments included dosing, consumption, bleeding, transfusions and haemostatic response. A population pharmacokinetics model of rFIXFc was used to predict FIX activity. Twelve subjects underwent 14 major surgeries (including 11 orthopaedic surgeries); most subjects (11/12) received rFIXFc prophylaxis before surgery (range, ~2 weeks-12 months). Investigators/surgeons rated haemostatic responses as excellent (n = 13) or good (n = 1). In most surgeries (85·7%), haemostasis from the pre-surgical dose until the end of surgery was maintained with a single rFIXFc infusion. Blood loss was consistent with similar surgeries in subjects without haemophilia. The strong correlation (R(2) = 0·9586, P < 0·001) between observed and population pharmacokinetic model-predicted FIX activity suggests surgery did not impact rFIXFc pharmacokinetics. No unique safety concerns or inhibitors were observed. In conclusion, rFIXFc was safe and efficacious, with prolonged dosing intervals and low consumption, when used perioperatively in haemophilia B. Surgery did not appear to alter rFIXFc pharmacokinetics.

Phase 3 study of recombinant factor VIII Fc fusion protein in severe hemophilia A.

This phase 3 pivotal study evaluated the safety, efficacy, and pharmacokinetics of a recombinant FVIII Fc fusion protein (rFVIIIFc) for prophylaxis, treatment of acute bleeding, and perioperative hemostatic control in 165 previously treated males aged ≥12 years with severe hemophilia A. The study had 3 treatment arms: arm 1, individualized prophylaxis (25-65 IU/kg every 3-5 days, n = 118); arm 2, weekly prophylaxis (65 IU/kg, n = 24); and arm 3, episodic treatment (10-50 IU/kg, n = 23). A subgroup compared recombinant FVIII (rFVIII) and rFVIIIFc pharmacokinetics. End points included annualized bleeding rate (ABR), inhibitor development, and adverse events. The terminal half-life of rFVIIIFc (19.0 hours) was extended 1.5-fold vs rFVIII (12.4 hours; P < .001). Median ABRs observed in arms 1, 2, and 3 were 1.6, 3.6, and 33.6, respectively. In arm 1, the median weekly dose was 77.9 IU/kg; approximately 30% of subjects achieved a 5-day dosing interval (last 3 months on study). Across arms, 87.3% of bleeding episodes resolved with 1 injection. Adverse events were consistent with those expected in this population; no subjects developed inhibitors. rFVIIIFc was well-tolerated, had a prolonged half-life compared with rFVIII, and resulted in low ABRs when dosed prophylactically 1 to 2 times per week.

Phase 3 study of recombinant factor IX Fc fusion protein in hemophilia B.

BACKGROUND: Prophylactic factor replacement in patients with hemophilia B improves outcomes but requires frequent injections. A recombinant factor IX Fc fusion protein (rFIXFc) with a prolonged half-life was developed to reduce the frequency of injections required. METHODS: We conducted a phase 3, nonrandomized, open-label study of the safety, efficacy, and pharmacokinetics of rFIXFc for prophylaxis, treatment of bleeding, and perioperative hemostasis in 123 previously treated male patients. All participants were 12 years of age or older and had severe hemophilia B (endogenous factor IX level of ≤2 IU per deciliter, or ≤2% of normal levels). The study included four treatment groups: group 1 received weekly dose-adjusted prophylaxis (50 IU of rFIXFc per kilogram of body weight to start), group 2 received interval-adjusted prophylaxis (100 IU per kilogram every 10 days to start), group 3 received treatment as needed for bleeding episodes (20 to 100 IU per kilogram), and group 4 received treatment in the perioperative period. A subgroup of group 1 underwent comparative sequential pharmacokinetic assessments of recombinant factor IX and rFIXFc. The primary efficacy end point was the annualized bleeding rate, and safety end points included the development of inhibitors and adverse events. RESULTS: As compared with recombinant factor IX, rFIXFc exhibited a prolonged terminal half-life (82.1 hours) (P<0.001). The median annualized bleeding rates in groups 1, 2, and 3 were 3.0, 1.4, and 17.7, respectively. In group 2, 53.8% of participants had dosing intervals of 14 days or more during the last 3 months of the study. In groups 1, 2 and 3, 90.4% of bleeding episodes resolved after one injection. Hemostasis was rated as excellent or good during all major surgeries. No inhibitors were detected in any participants receiving rFIXFc; in groups 1, 2, and 3, 73.9% of participants had at least one adverse event, and serious adverse events occurred in 10.9% of participants. These events were mostly consistent with those expected in the general population of patients with hemophilia. CONCLUSIONS: Prophylactic rFIXFc, administered every 1 to 2 weeks, resulted in low annualized bleeding rates in patients with hemophilia B. (Funded by Biogen Idec; ClinicalTrials.gov number, NCT01027364.).

The use of a fludarabine-based conditioning regimen in patients with severe aplastic anemia--a retrospective analysis from three Indian centers.

Between 2001 and 2009, 121 patients with severe aplastic anemia (SAA) underwent hematopoietic stem cell transplantation (HSCT) using a conditioning protocol of fludarabine and cyclophosphamide at three Indian hospitals. Donors were HLA-identical sibling or family donors. Seventy-six patients were considered "high risk" as per criteria. The graft source included peripheral blood stem cells in 109 and G-CSF-stimulated bone marrow in 12. GVHD prophylaxis consisted of cyclosporine and mini-methotrexate. Engraftment occurred in 117 (96.6%) while two had graft failure and two expired in the first two wk. Neutrophil engraftment was seen at 12.3 d (range: 9-19) while platelet engraftment occurred at 12.4 d (range: 8-32). Grade II-IV acute GVHD was seen in 26.7% and grade IV GVHD in 8.6%. Chronic GVHD occurred in 44% and was extensive in 10%. The five-yr overall survival for the entire cohort is 75.8 ± 3.9% with a survival of 95.6 ± 3.1% in the low-risk group (n = 45) and 64.0 ± 5.6% in the high-risk group (n = 76). Conditioning with fludarabine and cyclophosphamide is associated with very good long-term survival in patients undergoing HSCT for SAA.

Histopathological pattern of lymphomas and clinical presentation and outcomes of diffuse large B cell lymphoma: A multicenter registry based study from India.

CONTEXT: The distribution of various subtypes of lymphomas in India is different from other parts of the world. There is scarce multicentric data on the pattern and outcomes of lymphomas in India. AIMS: The aim of this study is to evaluate the histopathological and the clinical pattern and treatment outcomes of lymphomas in India based on the retrospective data collected from a multicenter registry. MATERIALS AND METHODS: Retrospective data was collected at 13 public and private hospitals in India for patients diagnosed with lymphoma between January 2005 and December 2009. The data collection was performed in the setting of a multicenter lymphoma registry Survival analyses were performed using the Kaplan-Meier method and compared using the log-rank test. RESULTS: Non-Hodgkin's lymphoma (NHL) constituted 83.17% and Hodgkin's lymphoma (HL) for 16.83% of the 1733 registered and analyzed cases. Diffuse large B cell lymphoma (DLBCL) was the most common NHL (55%) followed by follicular lymphoma (11%). CHOP was the most common chemotherapy regimen administered (84%) while rituximab was used in 42.7% of those with DLBCL. Survival analysis of treatment naïve DLBCL patients (n = 791) was performed. Of these, 29% were lost to follow-up, 20% with active disease. The median follow-up in surviving patients is 31 (range: 1-88) months. Median progression-free survival (PFS) and overall survival (OS) in DLBCL patients has not reached. There was no significant difference in median PFS (69 months vs. 61 months, P = 0.1341), but OS was significant not reached (NR) vs. NR, P = 0.0012) within international prognostic index high or intermediate subgroups. Rituximab use was associated with significantly prolonged PFS (NR vs. 82 months, P = 0.0123), but not OS (NR vs. NR, P = 0.2214). Cox regression analysis in treatment naïve DLBCL patients showed a performatnce status, stage and receipt of six or more cycles of chemotherapy to be significantly associated with OS and all of the preceding plus rituximab use significantly associated with PFS. CONCLUSIONS: Our analysis confirms previous reports of distribution of lymphoma subtypes in India and suggests that patients who are able to receive the full course of chemotherapy achieve a better outcome. This indicates the importance of ensuring compliance to treatment utilizing various measures including patient and family counseling. Prospective studies are required to confirm these findings.