Cost-effectiveness analysis of low-dose prophylaxis versus on-demand treatment for moderate-to-severe hemophilia A in India.

AIM: Hemophilia A (HA) is an inherited bleeding disorder caused by a deficiency of clotting factor VIII in the blood. In resource-limited settings like India, affordability is a significant challenge in managing patients with severe HA. This study aims to assess the cost-effectiveness of intermediate-dose prophylaxis versus on-demand factor therapy in adult and pediatric populations with moderate-to-severe congenital HA without inhibitors in India. METHOD: We conducted a prospective cost-effectiveness analysis from a societal perspective, categorizing patients into a base state and a joint disease state (patients with Hemophilia suffering extensive bleeds leading to chronic joint disease). Using targeted literature search and primary market research, we developed a Markov model measuring the total cost of Hemophilia treatment and health outcomes, including life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-utility ratio (ICUR), and incremental cost-effectiveness ratio (ICER). The model extended over a lifetime horizon of 70 years with a one-year cycle length. Sensitivity analyses assessed study robustness. RESULTS: Low-dose prophylactic therapy was cost-effective for adults (>18 years) and pediatric populations (<18 years), yielding better health outcomes (adults: 0.15 LYs and 2.43 QALYs gained; pediatric: 0.40 LYs and 3.12 QALYs gained). Intermediate-dose prophylaxis showed positive net monetary benefits in terms of Quality-Adjusted Life Years (QALYs) for both adult and pediatric populations, with dominant ICER and ICUR values in both cases. CONCLUSION: Using intermediate-dose prophylactic factor VIII therapy is a cost-effective approach that improves clinical outcomes compared to on-demand therapy in the Indian adult and pediatric HA populations without inhibitors.

Pattern of autologous stem cell transplants at a tertiary care government hospital, with emphasis on transplant outcomes with pre-harvest CD34+ level.

Purpose: Autologous stem cell transplantation (ASCT) is an established therapy for many hematological diseases. This study assessed the pattern of ASCTs at a tertiary care center and associated factors, including pre-harvest CD34+ stem cell levels, leading to improved engraftment outcomes. Methodology: A retrospective study was conducted in India, between February 2009-August 2020. Patients who underwent ASCT for different hematological malignancies (n=65) were included, and the patients' age, sex, type and stage of disease, pre- and post-harvest CD34+ counts, and time to attain platelet/neutrophil engraftment or febrile neutropenia were analyzed. The post-harvest CD34+ dose was calculated. Pre-conditioning was performed using Granulocyte Colony Stimulating Factor (GCSF)±Plerixafor. Progression-free survival (PFS) was calculated using relapse/death as the endpoint. Results: The median age of the cohort (n=65) was 49 years, with a male preponderance. Multiple myeloma was the most common malignancy (70.8% [46/65]), requiring ASCT. The median time to ASCT was 13 months. All patients had received GCSF, while Plerixafor was used in 17 patients with a pre-harvest CD34+ count of <10 cells/µL. The median pre-harvest CD34+ concentration and post-harvest CD34+ cell dose was 27.54 cells/µL (n=26) and 5.23×106 cells/kg body weight (n=65), respectively. The median time to engraftment was 11 and 12 days, for neutrophils and platelets, respectively. One patient did not engraft and was excluded from the analysis. The time required to attain neutrophil engraftment was significantly lower (p=0.02) among freshly harvested stem cells (n=48) than that of cryopreserved products (n=17). Platelet engraftment associated with CD34+ pre- and post-harvest levels was not significant (p=0.06). The time to attain neutropenia and subsequent febrile neutropenia was significantly lower with an adequate post-harvest CD34+ dose (p=0.009). Febrile neutropenia was seen in 83.1% (54/65) patients. The median time for febrile neutropenia was 4 days post-ASCT. Pre- and post-harvest CD34+ concentrations were directly proportional to each other (p<0.001). The median PFS was 112 months (n=65). Survival was better in males (median PFS: 112 months) vs. females (median PFS: 59 months) (p=0.27). Eight patients relapsed, and eight patients had died. Conclusion: Although unrelated to age or sex, the post-harvest CD34+ dose was inversely related to febrile neutropenia. As pre- and post-harvest CD34+ levels were directly proportional, pre-harvest CD34+ concentrations may be reliably used to assess engraftment outcomes. Rapid neutrophil engraftment was noted in fresh stem cells with PFS of 112 months, and was better among males, the exact reason being unknown. Thus, a larger number of patients should be followed up to obtain an accurate picture.

Response to Immunosuppressive Therapy in Acquired Aplastic Anaemia: Experience of a Tertiary Care Centre from Eastern India.

The current study was conducted to assess response to immunosuppressive therapy (IST) in acquired aplastic anaemia (AA). It was a retrospective and prospective observational study. Patients were diagnosed as per standard international guidelines and IST was started as per standard protocol. Patients were followed up at 3 months and 6 months for assessment of response as per published standard guidelines. Total 76 cases were included in the study. The median age of the study population was 36 years with a range of 6-66 years with a male to female ratio of 2.04:1. Most common clinical presentation was pallor followed by bleeding. Commonest type of disease in the study group was severe AA. Among total 76 patients, 32 patients received Atgam and 44 patients received Thymogam. Within 3 months of ATG administration, 4 patients died and 1 patient was lost to follow up. At 3 months, 2 (2.63%) patients were on complete response (CR), 32 (42.10%) patients were in partial response (PR) and 37 (48.68%) patients were on no response (NR). Overall response (OR) at 3 months was 44.73%. At 6 months 5 (6.57%) patients were in CR, 43 (56.57%) patients in PR and 23 (30.26%) patients in NR; the OR was 63.14%. Overall response at 3 months was 44.73% and overall response at 6 months was 63.14%. The study revealed better overall survival for patients with ATGAM treatment than THYMOGAM treatment arm.

Indian Society of Hematology and Blood Transfusion (ISHBT) Consensus Document on Hematological Practice During COVID-19 Pandemic.

The SARS-CoV-2 (COVID-19) pandemic is a worldwide public health emergency with widespread impact on health care delivery. Unforeseen challenges have been noted during administration of usual haematology care in these unusual COVID-19 times. Medical services have been overstretched and frontline health workers have borne the brunt of COVID-19 pandemic. Movement restrictions during lockdown prevented large sections of population from accessing health care, blood banks from holding blood drives, and disrupted delivery of diagnostic hematology services. The disruption in hematology care due to COVID-19 pandemic in India has been disproportionately higher compared to other subspecialities as hematology practice in India remains restricted to major cities. In this review we chronicle the challenges encountered in caring for hematology patients during the COVID-19 pandemic in India and put forth recommendations for minimizing their impact on provision of hematology care with special emphasis on hematology practice in lower and middle income countries (LMICs).

Comparison of efficacy and safety of thalidomide vs hydroxyurea in patients with Hb E-ß thalassemia - a pilot study from a tertiary care Centre of India.

INTRODUCTION: Hemoglobin (Hb)-F inducers are known to improve Hb level and transfusion dependence in thalassemia. This pilot study was conducted to assess the efficacy and safety of Hb-F inducer thalidomide compared to hydroxyurea (HU) in Hb E-ß thalassemia patients. METHODS: This was a prospective interventional single-centre study with 45 Hb E-beta thalassemia patients equally divided into group-I (thalidomide+folic acid), group-II (HU + folic acid) and group-III (folic acid). Response was assessed at various time intervals with 12-months follow up period. Primary end points were increment in Hb, Hb-F level and improvement in transfusion requirement; secondary end point were tolerability and safety. RESULTS: There was 100% responder (R: Hb-increment ≥1 g/dl) in group-I with 66.67% major responder (MaR: Hb-increment ≥2 g/dl), while there were 40% and 0% responder in group-II and III respectively. Hb-increment was significantly (p-value <0.0001) better in thalidomide arm compared to HU. The Hb-increment was attributable to both increase in Hb-F levels and reduction in ineffective erythropoiesis in thalidomide arm. Transfusion reduction was significantly better in group-I compared to group-II (100% vs 34%). No severe adverse effects was reported by patients of any group. CONCLUSION: Thalidomide showed a persistent significant Hb-increment and transfusion independence in Hb E-ß thalassemia patients compared to HU.

Utility of 18F-fluorodeoxyglucose PET-CT scan in detecting bone marrow involvement in lymphoma.

Background & objectives: Evaluation of bone marrow infiltration in lymphoma is usually done by bone marrow biopsy (BMB). This study analyzed the utility of 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) to detect bone marrow involvement (BMI) compared to BMB. Methods: Treatment-naïve lymphoma patients underwent both 18F-FDG PET/CT scan and BMB before treatment initiation. BMI detected on PET/CT was compared with BMB. Results: The study population consisted of 80 patients and comprised 37 Hodgkin's lymphoma (HL) patients, 30 aggressive non-HL (NHL) and 13 indolent NHL patients. The majority of the aggressive NHLs were diffuse large B-cell lymphoma (20/30) and major indolent lymphoma was follicular lymphoma (5/13). When compared to BMB, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of focal (±diffuse) marrow FDG uptake on 18F-FDG PET/CT were 100, 61.3, 33.3 and 100 per cent, respectively, for HL; 100, 65.4, 30.8 and 100 per cent, respectively, for aggressive NHL and 75, 80, 85.7 and 66.7 per cent, respectively, for indolent NHL. When comparing marrow involvement on 18F-FDG PET/CT to baseline BMB and/or resolution of bone marrow FDG uptake at interim/end-of-treatment 18F-FDG PET/CT, the sensitivity, specificity, PPV and NPV were 100 per cent each for HL and aggressive NHL and 77.3, 100, 100 and 66.7 per cent, respectively, for indolent NHL. Interpretation & conclusions: 18F-FDG PET/CT has a good sensitivity and NPV for detecting BMI in HL and aggressive lymphoma. The low specificity and PPV improved if marrow uptake pattern on interim or end-of-treatment 18F-FDG PET/CT scan was analyzed. In patients with HL who are staged with18F-FDG PET/CT at baseline and followed up with an interim/end-of-treatment PET/CT, baseline BMB may be avoided. For all other lymphoma subtypes, BMB may be essential if there is no marrow FDG uptake on PET/CT scan performed at baseline.

Effect of age, comorbidity and remission status on outcome of COVID-19 in patients with hematological malignancies.

BACKGROUND: There is scarcity of data on outcome of COVID-19 in patients with hematological malignancies. Primary objective of study was to analyse the 14-day and 28-day mortality. Secondary objectives were to correlate age, comorbidities and remission status with outcome. METHODS: Retrospective multicentre observational study conducted in 11 centres across India. Total 130 patients with hematological malignancies and COVID-19 were enrolled. RESULTS: Fever and cough were commonest presentation. Eleven percent patients were incidentally detected. Median age of our cohort was 49.5 years. Most of our patients had a lymphoid malignancy (n = 91). One-half patients (52%) had mild infection, while moderate and severe infections contributed to one-fourth each. Sixty seven patients (52%) needed oxygen For treatment of COVID-19 infection, half(n = 66) received antivirals. Median time to RT-PCR COVID-19 negativity was 17 days (7-49 days). Nearly three-fourth (n = 95) of our patients were on anticancer treatment at time of infection, of which nearly two-third (n = 59;64%) had a delay in chemotherapy. Overall, 20% (n = 26) patients succumbed. 14-day survival and 28-day survival for whole cohort was 85.4% and 80%, respectively. One patient succumbed outside the study period on day 39. Importantly, death rate at 1 month was 50% and 60% in relapse/refractory and severe disease cohorts, respectively. Elderly patients(age ≥ 60) (p = 0.009), and severe COVID-19 infection (p = 0.000) had a poor 14-day survival. The 28-day survival was significantly better for patients in remission (p = 0.04), non-severe infection (p = 0.00), and age < 60 years (p = 0.05). CONCLUSIONS: Elderly patients with hematological malignancy and severe covid-19 have worst outcomes specially when disease is not in remission.

Efficacy and safety profile of generic imatinib in patients with newly diagnosed chronic myeloid leukemia-chronic phase: sharing experience of a hemato-oncology center from eastern India.

In India, CML is the commonest adult leukemia. Imatinib is the gold standard for frontline treatment of newly diagnosed CML-CP patients. The present study was conducted to assess the efficacy and safety of generic imatinib in newly diagnosed CML-CP patients. In this prospective study, 76 newly diagnosed CML-CP patients received generic imatinib. They were monitored as per the ELN2013 recommendation. Karyotyping and BCR-ABL transcript level were done at specified time points. Adverse effects, if any, were documented as per the NCI-CTCAE criteria v4.03. Statistical analysis was done using standard methods. A total of 76 patients included in the study; median age was 36 years. The most common (71%) presenting symptom was fatigue; splenomegaly was found in all patients. CHR was achieved in 97% cases. At 3 months, 64.5% patients achieved ERM. At 6 months, CCyR and MCyR had seen in 65% and 68% cases, respectively. MMR achieved at 12 months in 44% cases. Most common hematological and non-hematological toxicity were anemia and skin changes seen in 89.5% and 71% cases, respectively. With generic imatinib therapy, the results of treatment outcome and safety profile were comparable with original imatinib. The added advantage was gross reduction in cost of therapy meeting unmet needs in CML patients in countries with resource constraints.

Efficacy of Dichlorophenolindophenol (DCIP) as Screening Test for Hb E: Revisited.

Hb E-beta thalassemia is a major public health problem in West Bengal, India and is the predominant symptom producing thalassemia in this part of the country. To search for an easy, reliable and cost effective screening method for HbE that can be used at the community level where more sophisticated methods are not readily available. And the DCIP test was performed for the purpose. Blood samples of 425 asymptomatic family members from 80 diagnosed cases of HbE beta Thalassemia patients were tested for Hb, RBC indices, DCIP test, HPLC, and in discordant cases confirmed by DNA mutation analysis. The present study shows DCIP screening test to have a sensitivity, specificity, positive predictive value and negative predictive value of 96.39%, 97.43%, 96.39% and 97.43% respectively. It also shows a false positive rate and false negative rate in 2.56% and 4.6% cases respectively. The advantage with DCIP over HPLC is that it can be easily performed at the community level by a person with minimum technical skill, few samples (even a single sample) can be tested at time, at a low cost.

Is Low Dose a New Dose to Initiate Hemophilia A Prophylaxis? - A Systematic Study in Eastern India.

OBJECTIVES: To investigate the effectiveness of low dose secondary/tertiary prophylaxis in severe Hemophilia A children and determine improvements in their daily life. METHODS: Thirty Hemophilia A children (≤ 12 y) with factor VIII <2% and less than two joint bleeds without inhibitors, were given prophylaxis with recombinant Fc fusion long acting factor VIII (ELOCTATE) at 10 IU.kg-1 twice weekly for 1 y. Earlier, patients received on-demand FVIII for a minimum of six months. Outcome was measured in terms of annual bleeding rate, Hemophilia Joint Health Score (HJHS) and child activity/participation was measured in terms of school absenteeism, School Activity Participation Score and Daily Activity Score according to Beijing Children Hospital assessment scale. RESULTS: A total of 30 children were included in the study. There was reduction in annual joint bleeds by 85.76% (14.5 to 2.2) and school absenteeism (days/month) by 86% (17.38 to 2.42) before and after prophylaxis respectively. Majority (43%) showed moderate improvement in daily activity score. Mean HJHS score was 8.3. There was mild improvement in School Activity Participation Score in 57%. Mean annual hospitalization rate reduced from 8.7 to 1.1 with improvement in joint scores. Mean annual factor consumption decreased from 1944.2 IU.kg-1 to 1560.3 IU.kg-1. CONCLUSIONS: With low dose secondary/tertiary prophylaxis, there is significant reduction in the annual joint bleed rate with improvement in joint health and child activity. As factor consumption is reduced, this has a positive effect on cost benefit; and is a very feasible option in developing countries.

Outbreak of Burkholderia Cepacia Infection: a Systematic Study in a Hematolooncology Unit of a Tertiary Care Hospital from Eastern India.

BACKGROUND: Burkholderia cepacia, an aerobic gram-negative bacillus, is a frequent colonizer of fluids used in the hospital ward. It poses little risk of infection to healthy people; however it is a known important opportunistic pathogen causing morbidity and mortality due to its intrinsic resistance to most of the antibiotics in hospitalized patients. Small hospital outbreaks are frequent. B. cepacia may occur as an opportunistic infection in hemato-oncology patients. Here we present an outbreak of Burkholderia cepacia infection in hematology ward of our institute. METHODS: Febrile episodes as defined by IDSA guideline, 2010 were followed, and blood for culture and sensitivity was sent in all the events. The culture was done by an automated method using Bactalert 3d Biomeriux & sensitivity pattern by Microscan Siemens method and subsequently detected by PCR based method. RESULTS: During September 2016 to February 2017 (six months), a total of 498 blood cultures were sent during febrile episodes. Out of which 60 (12%) came out to be positive for different microorganisms. Out of all positive cultures, Burkholderia cepacia was detected in 29 (48%) patients, which reduced drastically following the change in antibiotic administration practice. All isolates showed sensitivity to pipercillin+tazobactum, cefoperazone+sulbactum, fluoroquinolones, cotrimoxazole and carbapenems and resistance to polymyxin B and colistin. With timely intervention by appropriate intravenous antibiotics as per culture sensitivity result and change in antibiotic preparation practice, overall mortality was low 1 (4%) out of 29 culture positive episodes. CONCLUSION: Change of antibiotic preparation practice was the key to control this outbreak, and overall mortality was low.

Outcome of Cyclosporine Monotherapy in Patients of Aplastic Anemia: Experience of a Tertiary Care Hospital in Eastern India.

INTRODUCTION: Immune suppression is a crucial pillar for treatment of aplastic anemia. Cyclosporine monotherapy is an easily available, affordable therapeutic option with good safety profile. METHODS AND MATERIALS: This prospective study was conducted over a period of 2 years from June 2012 to July 2014. The diagnosis and response to treatment of aplastic anemia was established as per published criteria. Follow up was done at 3 and 6 months in order to assess the response. RESULTS: 57 patients of acquired aplastic anemia with median age of 37 years (6 to 81 years) were included in the study. 35 (62 %) cases were severe aplastic anemai, 16 (28 %) non severe aplastic anemia and 6 (10 %) were very severe aplastic anemia. At 3 months overall response rate (OR) was 7 (14 %) and at 6 months the OR rate of 11 (19.6 %) was achieved. Transiently raised creatinine, liver function abnormality and gum hypertrophy were the main side effects observed in this cohort. CONCLUSION: Oral cyclosporine monotherapy at dose of 5 mg/kg/day is a relatively safe treatment option for resource poor patients with aplastic anemia.

Platelet Aggregation Study in Patients With Hemoglobin Eß Thalassemia in India.

Hemoglobin Eß thalassemia is a major public health problem in India, especially in the state of West Bengal. Various thromboembolic events are common, especially in splenectomized patients. Platelet hyperactivity most likely plays a pathogenetic role. To investigate the role of platelets in hypercoagulability, platelet aggregation tests were undertaken in the present study. Platelet-rich plasma from 30 patients with Eß thalassemia (15 splenectomized and 15 nonsplenectomized) were studied and compared with 15 healthy participants. The 4 agonists used were adenosine 5-diphosphate, adrenaline (epinephrine), collagen, and ristocetin. The current study shows both splenectomized and nonsplenectomized patients had abnormal aggregation compared to normal healthy controls. Splenectomized patients had higher platelet aggregation than nonsplenectomized patients for all 4 agonists; but statistically significant difference among 2 groups was found only for collagen. The present study confirms a role of splenic absence in platelet hyperaggregation.

Does Profile of Hemoglobin Eß-thalassemia Patients Change After Splenectomy? Experience of a Tertiary Thalassemia Care Centre in Eastern India.

Hemoglobin Eß-thalassemia is by far the commonest form of thalassemia intermedia. Its phenotype ranges from mild anemia to severe transfusion-dependency necessitating splenectomy in many patients. The present study aimed to systematically analyze both clinical as well as laboratory parameters in profile of Eß-thalassemia patients after splenectomy in terms of transfusion requirement, infections and other complications. Retrospective study conducted over a period of 3 years included 72 cases of splenectomized Eß-thalassaemia patients, considering decrease in transfusion requirements, new complications, antibiotic, anti-malarial prophylaxis and iron chelation therapy. Out of 1380 registered Eß-thalassemia patients, 618 (44.78 %) were regularly transfused and 72(5.22 %) underwent splenectomy. Mean age of diagnosis was 10.3 years. Nineteen patients (26.4 %) underwent splenectomy between 5 and 10 years, 38 cases (52.7 %) between 10 and 20 years. The leading cause (51.39 %) for splenectomy was mechanical discomfort. Mean steady state hemoglobin raised from pre-splenectomy level of 5.43-6.8 gm/dl after splenectomy. Mean transfusion requirement reduced from 18.1 to 7.8 units/year. Mean serum ferritin level increased from 907.58 to 1,091.6 ng/ml. Post-splenectomy; 21 (29.17 %) patients developed facial deformities, 17 (23.6 %) delayed pubertal growth, 11 (15.28 %) venous thromboembolism, five (6.94 %) pulmonary hypertension and four (5.5 %) had extramedullary hematopoiesis. Five (6.96 %) patients had documented bacterial infections and two (2.78 %) suffered from malaria. Forty eight patients (66.67 %) started with iron chelation therapy; but majority (52.7 %) stopped. Major advantage of splenectomy is reduced transfusion requirement, though it cannot prevent skeletal abnormalities and delayed pubertal growth. In resource constraint countries like India, routine anti-malarial and antibacterial prophylaxis is not desirable; iron chelation therapy should be encouraged and ensured.