Chronic hepatitis B and occult infection in chemotherapy patients - evaluation in oncology and hemato-oncology settings: The CHOICE study.

BACKGROUND: Reactivation of hepatitis B virus (HBV) infection is a well-known risk that can occur spontaneously or following immunosuppressive therapies, including cancer chemotherapy. HBV reactivation can cause significant morbidity and even mortality, which are preventable if at-risk individuals are identified through screening and started on antiviral prophylaxis. AIM: To determine the prevalence of chronic HBV (CHB) and occult HBV infection (OBI) among oncology and hematology-oncology patients undergoing chemotherapy. METHODS: In this observational study, the prevalence of CHB and OBI was assessed among patients receiving chemotherapy. Serological markers of HBV infection [hepatitis B surface antigen (HBsAg)/anti-hepatitis B core antigen (HBc)] were evaluated for all patients. HBV DNA levels were assessed in those who tested negative for HBsAg but positive for total anti-HBc. RESULTS: The prevalence of CHB in the study cohort was determined to be 2.3% [95% confidence interval (95%CI): 1.0-4.2]. Additionally, the prevalence of OBI among the study participants was found to be 0.8% (95%CI: 0.2-2.3). CONCLUSION: The findings of this study highlight the importance of screening for hepatitis B infection in oncology and hematology-oncology patients undergoing chemotherapy. Identifying individuals with CHB and OBI is crucial for implementing appropriate antiviral prophylaxis to prevent the reactivation of HBV infection, which can lead to increased morbidity and mortality.

Whole Exome Sequencing Reveals Novel Variants in Unexplained Erythrocytosis.

Erythrocytosis is characterized by an increase in red cells in peripheral blood. Polycythemia vera, the commonest primary erythrocytosis, results from pathogenic variants in JAK2 in ∼98% of cases. Although some variants have been reported in JAK2-negative polycythemia, the causal genetic variants remain unidentified in ∼80% of cases. To discover genetic variants in unexplained erythrocytosis, we performed whole exome sequencing in 27 patients with JAK2-negative polycythemia after excluding the presence of any mutations in genes previously associated with erythrocytosis (EPOR, VHL, PHD2, EPAS1, HBA, and HBB). We found that the majority of patients (25/27) had variants in genes involved in epigenetic processes, including TET2 and ASXL1 or in genes related to hematopoietic signaling such as MPL and GFIB. Based on computational analysis, we believe that variants identified in 11 patients in this study could be pathogenic although functional studies will be required for confirmation. To our knowledge, this is the largest study reporting novel variants in individuals with unexplained erythrocytosis. Our results suggest that genes involved in epigenetic processes and hematopoietic signaling pathways are likely associated with unexplained erythrocytosis in individuals lacking JAK2 mutations. With very few previous studies targeting JAK2-negative polycythemia patients to identify underlying variants, this study opens a new avenue in evaluating and managing JAK2-negative polycythemia.

Supplemental Pioglitazone to Patients of CML with Suboptimal TKI Response: A Pragmatic Pilot Study.

Tyrosine kinase inhibitors (TKIs) have improved outcomes of chronic myeloid leukemia (CML). However, 20-30% of patients require second-line TKIs following suboptimal response. The cost and adverse events limit their use in resource-constraint settings. We conducted a pilot study to ascertain the benefit of adding pioglitazone to TKIs with suboptimal response in real-world resource-constraint settings. In this pragmatic pilot study from 01 Jan 2017 to 31 July 2021, CML patients from a tertiary care center in North India with sub-optimal response to TKIs were additionally given pioglitazone after ruling out imatinib resistance mutation (n - 31). Pioglitazone was stopped if there was disease progression on follow-up, and second-line TKI was started. The data were analyzed with the intention-to-treat principle using JMP Ver.15.1.1. The median age of the study population was 54y (27-82), who were followed up for a median duration of 1023.5d (59-1117). Pioglitazone showed the benefit of one-log reduction in BCR-ABL in 89.7% of the study participants. 1y, 2y and 3y-PFS were 92.57%, 76.5%, and 68.3% respectively. During follow-up period, the disease progressed in 38.7%, of which two succumbed. No adverse events to Pioglitazone were documented. This study proved that adding Pioglitazone to the existing TKI regime in CML with sub-optimal response can benefit. The addition of Pioglitazone was well tolerated. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01561-x.

Prolonged fever and pancytopenia in a case of severe dengue may be secondary hemophagocytic lymphohistiocytosis.

The diagnosis of secondary hemophagocytic lymphohistiocytosis (HLH) in the setting of dengue fever is usually challenging but should be kept in mind in patients with persistent fever, pancytopenia, and multiorgan dysfunction. We report a case of severe dengue who had prolonged fever with multiorgan involvement, laboratory features fulfilling the diagnostic criteria of HLH, and had a prompt response with high-dose corticosteroids. Physicians should be aware of this rare clinical syndrome and its variable clinical presentations so that fatal outcomes can be prevented with prompt and appropriate treatment.

Clinical Spectrum of Rheumatic Manifestations in HIV Infected Males at a Tertiary Care Hospital.

BACKGROUND: In the current era of effective Anti retroviral therapy (ART), and Human Immunodeficiency Virus (HIV) infection becoming a chronic illness, there has been a gradual rise in the prevalence of rheumatic manifestations associated with this disease. These are characterized by a modified clinical course and widened spectrum of a few emerging rheumatic manifestations seen with HIV infection. AIMS AND OBJECTIVES: To assess the type, frequency, prevalence and clinical spectrum of rheumatic manifestations among &male patients followed at an HIV clinic of a tertiary care defence hospital. MATERIALS AND METHODS: All male patients with confirmed HIV infection at the study centre were studied after obtaining informed consent. A detailed history was taken including the date of seropositivity, symptoms of rheumatic disease, family history of rheumatic illness, and treatment history with ART. A detailed general and systemic examination was performed and rheumatic symptoms guided appropriate investigations were carried out on as required basis. RESULTS: 879 confirmed HIV cases were evaluated for rheumatic manifestations during the study period. Of these 499 cases were newly detected HIV cases and the rest 380 were old cases on follow up. Rheumatic disorders were diagnosed in 16 cases (1.82%). Spondyloarthropathy was the commonest presentation i.e. 5 out of 16 cases (31.25 % of the rheumatic disorders). Mean age was 37 years (range 27-52 yrs). 2 patients of the study group had the rheumatic illness prior to detection of HIV. Psoriatic Arthritis (0.114 %) was seen in 1 patient who was HLA B-27 negative. Reactive arthritis (0.227 %) was noted in 2 patients. 1 patient had cutaneous small vessel vasculitis (0.114 %), whereas 1 of the patient developed DLE (0.114 %) over neck. HIV related non specific polyarthritis (0.114 %) of the large joints was noted in 1 patient who was RF negative, while polyarthralgia (0.340 %) was noted in 3 patients. 10 patients (60 %) had CD 4 count < 200 cells/ µL, whereas 6 patients had a CD 4 count between 200 and 500 cells/µL. 13 out of 16 patients detected to have rheumatic illnesses were on ART. CONCLUSION: With the advent of ART, the clinical spectrum of HIV infection is changing as a chronic treatable disease. Present study consisting mainly adult males, showed only 1.82 % prevalence of rheumatic disorders in HIV infection. Early diagnosis, availability of ART and prompt treatment of opportunistic infections have changed the clinical profile of HIV patients. Impact of ART in producing and affecting the clinical spectrum of rheumatic disease has to be kept in mind while treating HIV-infected patients.

Open-label randomized control trial of hydroxychloroquine in patients with moderate to severe coronavirus disease 2019 infection.

BACKGROUND: At onset of coronavirus disease 2019 (COVID-19) pandemic, hydroxychloroquine (HCQ) was repurposed for treatment of patients based on reports that it had in vitro activity. The aim of this study was to find out if HCQ reduces number of days of hospitalization when given to patients with moderate to severe COVID-19 infections who require hospitalized care. METHODS: This was an open-label randomized control trial of HCQ administered 400 mg twice on day 1, then 400 mg once daily from day 2 to day 5 in patients with moderate to severe COVID-19 infection. Assessment was not blinded. Standard of care was given to both arms.Primary outcome was number of days of hospitalization till discharge or death. RESULT: One hundred ten patients (55 in each arm) were included. Mean age was 58 years. Baseline characteristics were well matched. There was no difference in the primary outcome (13.67 vs 13.89; p = 0.98). Number of deaths were more in HCQ arm (RR: 1.81; 95% CI: 1.13-2.93; p = 0.03). There was no difference in number of days on oxygen or normalization of oxygen saturation, number who needed ventilator, days to ventilator requirement and days on ventilator. Twenty-nine patients in control arm received remdesivir. When adjusted analysis was done after removal of these patients, there was no difference in primary or secondary outcomes. Number of deaths in adjusted analysis were not significant (RR: 1.28; 95% CI: 0.87-1.88; p = 0.37). CONCLUSION: HCQ does not change the number of days of hospitalization when compared with control.

The clinical profile, management, and outcome of febrile neutropenia in acute myeloid leukemia from resource constraint settings.

INTRODUCTION: Acute myeloid leukemia (AML) is the commonest leukemia in adults. Mortality in thew first 30-days ranges from 6% to 43%, while infections account for 30-66% of early deaths. We aim to present our experience of infections in newly-diagnosed AML. METHOD: This prospective, observational study, was undertaken at a tertiary care hospital in Northern India. Patients with confirmed AML (bone marrow morphology and flow cytometry) and who had developed febrile neutropenia (FN), were included. RESULT: A total of fifty-five patients were included in the study. The median age of the patients was 47.1 years (12-71) and 28 (50.9%) were males. Fever (33, 60%) was the commonest presentation at the time of diagnosis. One or more comorbid conditions were present in 20 patients (36.36%). Infection at presentation was detected in 17 patients (30.9%). The mean duration to develop febrile neutropenia since the start of therapy was 11.24 days. With each ten-thousand increase in white blood cell (WBC) count, the mean number of days of FN development decreased by 0.35 days (p = 0.029). Clinical and/or radiological localization was possible in 23 patients (41.81%). Thirty-four blood samples (34/242, 14.04%) from 26 patients (26/55, 47.3%) isolated one or more organisms. Gram negative bacilli (GNB) were isolated in 24 (70.58%) samples. Burkholderia cepacia (8/34, 23.52%) was the commonest organism. The number of days required to develop febrile neutropenia was inversely associated with overall survival (OS). However, when compared, there was no statistically significant difference in OS between patients developing fever on day-10 and day-25 (p = 0.063). Thirteen patients (23.63%) died during the study period. DISCUSSION: Low percentage of blood culture positivity and high incidence of MDR organisms are a matter of concern. Days to develop febrile neutropenia were inversely associated with overall survival (OS), emphasizing the importance of preventive measures against infections. CONCLUSION: Infections continues to be a major cause of morbidity and mortality among AML patients.

Safety and efficacy of azathioprine in immune thrombocytopenia.

BACKGROUND: Immune thrombocytopenia (ITP) is a benign hematological disorder characterized by low platelet counts in peripheral blood and spectrum of various bleeding manifestations. Azathioprine is one of the effective, readily available, and affordable immunosupressants available for ITP management in developing countries. We aimed to study the efficacy and long-term safety profile of our patients with ITP who were treated with azathioprine. METHOD: This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India. The patients who had received at least one line of therapy before receiving azathioprine were included in this study. All patients received oral azathioprine at a dose of 1 mg/kg/day (50 mg or 100 mg tablet formulations were used), which was increased up to 2 mg/kg/day depending upon the response and adverse effects. RESULT: Sixty-three patients were analyzed. Their median age was 28 years (range 15-68); 29/63 patients (46.03%) were females. The median duration from diagnosis to azathioprine initiation was 539 days (323 days-980.5 days). The patients included in the study had received a median of 3 (range 1-6) prior lines of therapies; 38/63 patients (60.32%) had received ≥3 prior therapies. Six patients (9.5%) had relapsed after splenectomy, and 16 patients (25.4%) had relapsed after receiving rituximab. The mean baseline platelet count was 10000/µL. The median time to response was 95 days (90 days-not reached) and the cumulative overall response rate (complete and partial response) at day 90 was 38.1%. Only one patient achieved complete response with azathioprine in our study. The cumulative rate of relapse at five years was 21.2%. Twenty-six patients stopped azathioprine after achieving some response (CR/PR) with Azathioprine for a median duration of 1067.5 days (range: 236 days-2465 days). They were followed up for a median of 870 days (range: 392 days-1928 days), and twelve of them relapsed. Twenty-six patients (26/63, 41.27%) reported one or more adverse events while on azathioprine. Leucopenia was the most frequent adverse event, followed by anemia and hepatobiliary laboratory abnormalities. Serious adverse events (grade ≥3 CTCAEv4) were noted in three patients (4.7%). One patient succumbed to severe sepsis multiorgan dysfunction while being on treatment. CONCLUSION: We conclude that azathioprine has a good response rate in chronic ITP patients. It is well-tolerated with minimal and manageable side effects.

Dissecting Primary Erythrocytosis Among Polycythemia Patients Referred to an Indian Armed Forces Hospital.

Referrals for evaluation of polycythemia cases have increased since the hemoglobin (Hb) thresholds for diagnosis of Polycythemia Vera (PV) have been lowered by WHO. The current study enrolled patients of age > 18 years from the Indian Armed Forces or their family members with polycythemia from November 2016 to October 2018. After exclusion of secondary causes, 49 patients were diagnosed as Primary Erythrocytosis (PE). The patients were classified into two groups: PV and Idiopathic Erythrocytosis (IE) and a systematic comparison of clinical and laboratory features of the two groups was done. The prevalence of PV in PE was 20.4% (10 of 49) while the rest 39 (79.6%) had IE. Seven PV patients had JAK2 V617F mutation, one had JAK2 Exon12 mutation, and two were JAK2 negative PV. Nine of 10 (90%) PV patients had Hb > 18.5 g/dl, while only 21 of 39 (53.8%) IE patients had Hb > 18.5 g/dl (p = 0.06). None of the JAK2 mutated patients had Hb < 18.5 g/dl. We conclude that PV is more prevalent in patients of PE with Hb > 18.5 g/dl. Most patients with Hb between 16.5-18.5 g/dl would still be classified as IE. We advocate the need for further studies evaluating the utility of investigating all patients of PE with the revised WHO Hb threshold as well as studies on genetic profile of IE patients from India.

Autologous Stem Cell Transplantation for Multiple Myeloma: Single Centre Experience from North India.

Autologous stem cell transplantation (ASCT) is considered as standard of care in patients with multiple myeloma (MM) patients aged 65 years or younger. We analyzed data of 94 patients of plasma cell dyscrasias who underwent 95 autologous transplants at our institute from October 2003 to Aug 2016. Other than 76 patients of newly diagnosed multiple myeloma, we also transplanted two patients of POEMS syndrome, two patients of plasma cell leukemia, three patients of concurrent light chain deposition disease, three patients of multifocal plasmacytomas, and eight patients of isolated light chain myeloma. One patient underwent transplant twice. The median age of patients was 53 years (range 21-65). The average interval between diagnosis and transplant was 10.51 ± 5.42 months. The predominant stage in the study cohort was ISS-III. IgG kappa was the commonest subtype of plasma cell dyscrasia (27.9%) followed by IgG lambda (16.27%). Renal involvement was seen in 25% patients at the time of transplantation. Following chemotherapy, 42% patients were in CR, 39% in VGPR, 5% had PR and 14% had progressive disease at the time of transplantation. All patients were conditioned with melphalan (dose 120-200 mg/m2) except for one who received an additional bortezomib for his second transplant. The mean time to neutrophil and platelet engraftment was 11.09 ± 1.82 and 12.69 ± 4.55 days respectively. Mucositis was noted in all patients (grade 3 in 37.5% patients). The median PFS (biochemical) was 55.8% and PFS (clinical) was 76.7% at 6.5 years. Thirteen percent of the transplanted patients succumbed to their illness of which three patients died within 30 days of transplant. Median OS was 76.7% at 6.5 years. ASCT is a feasible option for MM in India and the results are comparable.

Danazol increases T regulatory cells in patients with aplastic anemia.

OBJECTIVES: Danazol is an attenuated androgen and is used in the treatment of aplastic anemia (AA) in resource constraint settings. We chose to study the role of CD4+ CD25high CD127low FoxP3+ T regulatory cells (T-regs) in the pathophysiology of AA and their response to treatment with Danazol alone or in combination with immunosuppressive treatment (IST). METHODS: T-regs' percentages of 25 acquired idiopathic AA patients and 25 healthy controls who completed study protocol were analyzed by performing multicolor flowcytometry on peripheral blood samples. RESULTS: More than one-third (36%) of AA patients in our study received Danazol as monotherapy, whereas less than a third (32%) each received standard doses of IST with equine Anti Thymocyte Globulin (ATG) and Cyclosporine combination, or Cyclosporine and Danazol combination, respectively. Results showed that all AA patients had a significantly lower percentage of T-regs at the time of diagnosis when compared to healthy controls (p < 0.0001), implicating their role in the pathophysiology. On treatment, all 25 patients showed a significant rise in the percentage of T-regs when compared to baseline (p < 0.0001). DISCUSSION: The rise in T-regs' percentage was higher in patients treated with Danazol alone when compared to standard IST (ATG with Cyclosporine), or Cyclosporine with Danazol combinations (p = 0.585). CONCLUSION: We conclude that Danazol also leads to increase in T-regs in acquired idiopathic AA.