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Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high-risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate- and high-risk disease received a further 2 years of maintenance with ATRA, 6-mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow-up. The mean (SD) estimated 5-year event-free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5-year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long-term outcomes in the real-world setting.

COVID-19, the disease caused by SARS-CoV-2, is characterized by significant abnormalities of the hematopoietic as well as the hemostatic system. These abnormalities have important prognostic as well as therapeutic implications in the management of these patients. Lymphopenia has emerged as a cardinal manifestation of COVID-19, which correlates with the severity of the cytokine storm and confers an adverse prognosis. Although not associated with direct cytopathic effects of SARSCoV- 2, anemia and thrombocytopenia are commonly present, with increased incidence in critically ill patients. It has been suggested that an ineffective adoptive immune response may be responsible for the hyper-inflammatory state and cytokine response in patients with severe COVID-19. Dysregulation of the macrophage phenotype may be associated with secondary HLH like physiology with hyperferritinemia and multi-organ dysfunction. The coagulation abnormalities are characterized by normal or elevated fibrinogen levels and are distinct from DIC. This distinct coagulopathy is labelled as COVID coagulopathy. It is predominant due to local microangiopathy and endothelial dysfunction in involved organs, such as the pulmonary vasculature. The hypercoagulable state is associated with a higher risk of arterial and venous thrombosis and a trend towards an increase in vaso-occlusive events, such as myocardial infarction and stroke. The D-Dimer elevation is seen in approximately 50% of patients, and increasing value during hospitalization indicates a poor prognosis. Finally, a comprehensive understanding of these pathophysiological states may help us in devising treatment protocols with a combination of antiviral, anti-inflammatory, and anticoagulation strategies for best treatment outcomes.

The current pandemic coronavirus, SARS-CoV-2, is known to cause severe infection (COVID-19) in patients with comorbidities, particularly cancer or an immunosuppressed state. Most healthcare systems in the country are likely to be overwhelmed soon if the pandemic moves to a stage of community transmission. Currently, limited evidence is available for managing patients with hematological disorders during the COVID-19 pandemic. The current review summarises the possible challenges clinicians are likely to face, key considerations to guide decision making, and possible solutions to the anticipated challenges. Disease specific recommendations and possible guidance for decision making have been suggested for most hematologic diseases that are feasible in our health setup. It is not meant to replace individual clinical judgment, but to provide a template to formulate local policies.

Recent studies in iron-depleted women have challenged the current approach of treating iron-deficiency anemia (IDA) with oral iron in divided daily doses. Alternate day dosing leads to more fractional absorption of iron. In this randomized controlled trial, we looked at the efficacy and safety of alternate-day (AD) versus twice-daily (BD) oral iron in all severity of IDA. Total of 62 patients were randomized, 31 patients in BD arm received 60 mg elemental iron twice daily while 31 patients in AD arm received 120 mg iron on alternate days. The primary endpoint of 2 g/dl rise in hemoglobin was met in significantly more patients in the BD arm at 3 weeks (32.3% vs. 6.5%, p < 0.0001) and 6 weeks (58% vs. 35.5%, p = 0.001). There was a significant rise in the median hemoglobin at 3 (1.6 vs. 1.1, p = 0.02) and 6 weeks (2.9 vs. 2.0 g/dl, p = 0.03) in the BD arm. However, the median hemoglobin rise in the AD arm at 6 weeks was not significantly different than the BD arm at 3 weeks. Alternate-day dosing for 6 weeks and twice-daily dosing for 3 weeks resulted in the provision of the same total amount of iron. There were more reports of nausea in the BD arm (p = 0.03). In conclusion, the choice of twice-daily or alternate-day oral iron therapy should depend on the severity of anemia, the rapidity of response desired, and patient preference to either regimen due to adverse events. Trial Registration: CTRI reg. no. CTRI/2018/07/015106 http://ctri.nic.in/Clinicaltrials/login.php.

Lenalidomide maintenance after frontline chemo-immunotherapy (CIT) in chronic lymphocytic leukemia (CLL) has not been standard due to the availability of novel therapies, though these remain out of reach for most in low-middle income countries. This single-center, open-label study randomized CLL patients (non-deletion 17p) after frontline therapy to lenalidomide maintenance (dose-escalated 2.5-10mg, 20/28 days per cycle for six months) or observation (2:1 allocation). Forty patients were included over 2018-2020. At a median follow-up of 22 months, median progression-free survival (PFS) with lenalidomide was not significantly different than observation (26 vs. 18 months

Both innovator and generic imatinib are approved for the treatment of Chronic Myeloid Leukemia-Chronic phase (CML-CP). Currently, there are no studies on the feasibility of treatment free remission (TFR) with generic imatinib. In a single center prospective Generic Imatinib Free Trial - in -CML-CP (GIFT-in-CML-CP) study, twenty-six patients on generic imatinib for more than 3 years and in sustained deep molecular response (BCR ABLIS

To report the efficacy, safety, and quality of life (QoL) on generic and innovator ibrutinib in Indian CLL patients. This was a single centre, prospective study of treatment-naive (TN), and relapsed/refractory (R/R) CLL patients receiving ibrutinib in India. The choice of innovator or generic ibrutinib was as per patient discretion. Response and adverse events were recorded as per the 2018 iwCLL guidelines and CTCAEv4.0. QoL was assessed using the EORTC QLQ-C30 and CLL17 questionnaires. A total of 32 CLL patients (TN, n = 7 and R/R, n = 25) received ibrutinib from 2016–2019. The median age was 60 years (37–84). All TN patients attained partial response without any grade 3/4 adverse events (AE). Ibrutinib was less tolerated in the R/R setting, with 52% patients developing grade 3/4 AE and required dose reduction. Eleven patients (44%) died during follow-up. Grade 3–5 infections were seen in 44% of R/R CLL patients. Generic ibrutinib (n = 8) was comparable to innovator ibrutinib (n = 17) in terms of efficacy, safety, and QoL. Ibrutinib is less well tolerated in Indian R/R CLL patients. Infections are a common cause of morbidity and mortality. This study affirms the safety and efficacy of generic ibrutinib. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s12288-020-01378-6) contains supplementary material, which is available to authorized users.

INTRODUCTION The quality of life (QoL) analysis is likely to differ by region, ethnicity, and questionnaires in comparison with age-matched healthy controls. METHODS The EORTC QLQ-C30 and QLQ-CLL17 questionnaire validated in regional languages were administered to 127 consecutive CLL and 100 age-matched, healthy controls at a single center from 2018 to 2019. RESULTS All groups of CLL patients either on wait and watch (W&W) or on treatment had significantly impaired QoL in all functional domains including global health compared to controls (P

Carfilzomib is an irreversible proteasome inhibitor currently approved for the treatment of relapsed multiple myeloma. It has been implicated as a cause of thrombotic microangiopathy (TMA) in several case reports. The incidence, risk factors, and treatment of carfilzomib-related TMA remain unclear. Here we describe the clinical presentation and outcome of a 58-year-old man with biopsy-proven TMA that occurred following treatment with carfilzomib-based therapy. We also reviewed the published literature with regard to the incidence, risk factors, treatment options, and outcome of carfilzomib-related TMA.

A 63-year-old woman presented to a local centre after an episode of transient chest pain. A chest X-ray revealed mediastinal widening with well-rounded margins ([figure 1][1]). A contrast-enhanced CT was done which showed multiple paravertebral masses ([figure 2][2]). She was subsequently seen in

PURPOSE Chronic lymphocytic leukemia (CLL) is uncommon in India. There are limited studies on CLL from the Indian subcontinent. METHODS This was a prospective study (2011-2017) of consecutively diagnosed patients with CLL at a single center. The diagnosis, prognosis, treatment indication, response criteria, and adverse events were recorded as per International Workshop on Chronic Lymphocytic Leukemia guidelines. Biosimilar rituximab dosing (375 mg/m2) was fixed for all cycles. Time to next treatment (TTNT) was defined as the time from front-line treatment initiation to next treatment or death from any cause. Overall survival (OS) was defined as the time from treatment initiation until death from any cause. RESULTS A total of 409 patients with CLL were enrolled over the study period. The median follow-up was 32 months (range, 2-135 months). The median age was 61 years, and 31.8% of patients with CLL were ≤ 55 years of age; 43.3% of patients had a cumulative illness rating scale score ≥ 3. Prognostic fluorescence in situ hybridization data were available in 53.3% of patients. Chlorambucil (94/180; 52.2%) and bendamustine + rituximab (BR; 57/180; 31.6%) were the most common regimens used up front. The overall response rates after front-line therapy were 74.4% and 91.2%, respectively. The TTNT was 33 months and not reached, respectively ( P = .001). Grade 3/4 neutropenia and infections were seen in 52.6% and 38.5% of patients receiving BR. The median OS was not reached in both regimens ( P = .25). CONCLUSION Indian patients with CLL are younger in chronological age but have higher morbidity burden. Treatment outcomes with biosimilar fixed-dose BR are comparable to those reported in the literature. Chlorambucil is still a valid option, given the economic burden of the disease and treatment.

The need for prognostication in chronic lymphocytic leukemia (CLL) is felt due to the heterogeneous clinical course of CLL, to counsel the patients, tailor follow-up, and to guide treatment decisio...

Recent studies in iron-depleted women have challenged the current approach of treating iron-deficiency anemia (IDA) with oral iron in divided daily doses. Alternate day dosing leads to more fractional absorption of iron. In this randomized controlled trial, we looked at the efficacy and safety of alternate-day (AD) versus twice-daily (BD) oral iron in all severity of IDA. Total of 62 patients were randomized, 31 patients in BD arm received 60 mg elemental iron twice daily while 31 patients in AD arm received 120 mg iron on alternate days. The primary endpoint of 2 g/dl rise in hemoglobin was met in significantly more patients in the BD arm at 3 weeks (32.3% vs. 6.5%, p0.0001) and 6 weeks (58% vs. 35.5%, p = 0.001). There was a significant rise in the median hemoglobin at 3 (1.6 vs. 1.1, p = 0.02) and 6 weeks (2.9 vs. 2.0 g/dl, p = 0.03) in the BD arm. However, the median hemoglobin rise in the AD arm at 6 weeks was not significantly different than the BD arm at 3 weeks. Alternate-day dosing for 6 weeks and twice-daily dosing for 3 weeks resulted in the provision of the same total amount of iron. There were more reports of nausea in the BD arm (p = 0.03). In conclusion, the choice of twice-daily or alternate-day oral iron therapy should depend on the severity of anemia, the rapidity of response desired, and patient preference to either regimen due to adverse events. Trial Registration: CTRI reg. no. CTRI/2018/07/015106 http://ctri.nic.in/Clinicaltrials/login.php.

Convalescent plasma (CP) therapy is one of the promising therapies being tried for COVID-19 patients. This passive immunity mode involves separating preformed antibodies against SARS-CoV-2 from a recently recovered COVID-19 patient and infusing it into a patient with active disease or an exposed individual for prophylaxis. Its advantages include ease of production, rapid deployment, specificity against the target infectious agent, and scalability. In the current pandemic, it has been used on a large scale across the globe and also in India. However, unequivocal proof of efficacy and effectiveness in COVID-19 is still not available. Various CP therapy parameters such as donor selection, antibody quantification, timing of use, and dosing need to be considered before its use. The current review attempts to summarize the available evidence and provide recommendations for setting up CP protocols in clinical and research settings.

Hemophilia is an X-linked hereditary disorder. The worldwide incidence is 1 in 5000 (hemophilia A) and 1 in 30 000 (hemophilia B).1 Treatment for hemophilia includes deficient factor replacement with clotting factor concentrates (CFCs). CFCs are also used for acute hemophilic arthritis, along with rest, ice, compression, and elevation. There are many challenges for people with hemophilia, the most common of which are joint bleeds and deformity, which affect quality of life. Life-threatening visceral bleeding is not uncommon in hemophiliacs. Surgical intervention for hemophilia-related events that require it is always a demanding task, and the high cost of therapy is an obstacle to getting the necessary treatment. The following challenges are unique to the Indian population1-3: India has the second largest population of any country in the world. India has a high patient load: the total number of registered people with hemophilia is 18 353. Treatment for hemophilia is unaffordable for many. Less than 20% of the country’s population is covered by health insurance. India has a diverse geography. Many facilities that diagnose hemophilia are of poor quality. Care is suboptimal because many treatment facilities are of poor quality. Indians with hemophilia have a high rate of complications and disabilities.