Randomized controlled trial of twice-daily versus alternate-day oral iron therapy in the treatment of iron-deficiency anemia.

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.

Hematopoietic stem cell donor with IgA nephropathy: Challenges and management algorithm.

Donor safety is of prime importance in allogeneic hematopoietic cell transplantation. The Worldwide Network for Blood and Marrow Transplantation (WBMT) standing committee on donor issues has issued a consensus statement regarding suitability criteria for related adult donors. This committee recommends that donors with a history of immune-mediated glomerulonephritis and abnormal urine tests should preferably undergo bone marrow harvest, to avoid the theoretical risk of granulocyte colony-stimulating factor (G-CSF) induced immune flare-up. We discuss here a unique situation where a related donor with a history of IgA nephropathy (IgAN) insisted on a peripheral blood stem cell harvest. We propose a management plan for this situation, which posed challenges about donor suitability.

Pulmonary and Ear, Nose and Throat (ENT) Involvement in ANCA-Associated Vasculitis at Diagnosis-Experience from a Tertiary Care Centre in North India.

BACKGROUND AND AIMS: There is paucity of data on pulmonary and ENT involvement in ANCA associatd vasculitis from India. We aimed to review the pattern of lung and upper respiratory tract involvement in patients with AAV diagnosed at our centre. METHODS: A retrospective review of all AAV patients between January 2007 and June 2014 was done. A complete clinical evaluation for Pulmonary and ENT involvement was done. Advanced investigations including computed tomography (CT) bronchoscopy and nasal endoscopy were done when indicated. Proportion of involvement was noted and different variables among patient groups were compared. RESULTS: 92 patients (median age 42 years; 60% female) of AAV were included. Clinical and/or radiological evidence of lung involvement was seen in 70 (76.1%) patients. Diffuse alveolar haemorrhage was present in 6 (60%) patients with MPA and 7 (10.1%) patients with GPA (p=0.002). ENT involvement was present in 55 (59.8%) patients and was more in GPA (p=0.000). Absence of renal involvement [p=0.047] and absence of GI involvement [p=0.012] were associated with ENT involvement in GPA. CONCLUSION: Pulmonary involvement was common in GPA, MPA and CSS, ENT involvement was almost characteristic of GPA. DAH was common in MPA. Population based and multicentre studies are needed to assess the true burden of organ involvement in AAV in the Indian population.

Outcomes of Patients Diagnosed With Chronic Lymphocytic Leukemia After Allogeneic Hematopoietic Stem Cell Transplantation: Results From a Tertiary Care Center.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HCT) is currently the only curative treatment for patients with chronic lymphocytic leukemia (CLL). METHODS: We analyzed the outcomes of 93 patients (median age: 52 years) who underwent allo-HCT at our center between 1989 and 2019. RESULTS: After a median follow-up of 35 months, relapse was observed in 15.1% (n = 14) patients. The estimated 2-year non-relapse mortality, relapse-free survival, and overall survival (OS) were 38.1%, 54.2%, and 58.7%, respectively. The ECOG performance status ≥ 2 (hazard ratio [HR]: 4.1; p = .001) and use of total body irradiation (in a myeloablative conditioning regimen; HR: 2.64; p = .005) were predictive of poor OS after multivariable analysis. The occurrence of sinusoidal obstruction syndrome/veno-occlusive disease post-transplant was associated with poor survival (p = .001). CONCLUSION: Although the use of kinase and bcl2 inhibitors may result in a decrease in the number and need of transplants, allo-HCT remains a viable option in selected patients with high-risk CLL and good performance status.

Percutaneous catheter drainage of uncomplicated amoebic liver abscess: prospective evaluation of a clinical protocol for catheter removal and the significance of residual collections.

INTRODUCTION: Patients with amoebic liver abscess (ALA) may require percutaneous catheter drainage (PCD). Once the PCD output is substantially reduced or has ceased along with clinical recovery, residual collections on radiological evaluation may concern the treating physicians. The prevalence and significance of such collections is unknown, and the subsequent approach how to tackle them is unclear. METHODS: Consecutive patients with one or more uncomplicated ALAs requiring drainage were prospectively enrolled from 3 hospitals and managed based on a standard approach. Catheter removal was attempted after the patients fulfilled all 4 of the following criteria: disappearance of abdominal pain, absence of fever for at least 48 h, an improving trend of TLC (documented on 2 consecutive reports), and catheter drain output of < 10 ml/day for at least 2 consecutive days. RESULTS: A total of 110 patients (mean age 46.6 ± 10.5 years, 93.6% males, 89.1% alcoholics) underwent PCD placement; 69 patients (69/110; 62.7%) met all 4 criteria within 5 days of PCD placement (optimal response) and had an uncomplicated course. Patients with suboptimal responses (41/110; 37.3%) were evaluated for local and systemic complications; the appearance of fresh collections (5/110; 4.5%), abscess rupture (2/110; 1.8%), bile leakage (3/110; 2.7%), cholangitis (2/110; 1.8%), thrombophlebitis (2/110; 1.8%) and hospital-acquired infections (2/110; 1.8%) were diagnosed and treated accordingly. Ultimately, PCD removal (based on the fulfilment of all 4 criteria) was universally successful after a median of 5 days (IQR, 4-9 days). None of the patients had symptom recurrence after PCD removal, although residual collections were still seen in 97.3% of patients at the time of PCD removal and in 92.1% and 84.9% of patients available for follow-up at 1 and 3 months, respectively. CONCLUSION: Based on our clinical protocol, PCD removal in ALA can be successfully expedited even in the presence of residual collections. An inability to fulfill all 4 criteria within 5 days of PCD placement warrants further evaluations for local and systemic complications that require additional therapeutic measures.

Long-term outcomes of innovator versus generic melphalan formulation in autologous hematopoietic cell transplantation for multiple myeloma.

BACKGROUND: Most data on autologous hematopoietic cell transplantation (auto-HCT) in myeloma are based on the use of innovator formulation of melphalan. Comparative bioequivalence and efficacy studies of generic melphalan are lacking. METHODS: In this retrospective study, we report long-term outcomes of auto-HCT in myeloma using innovator (Alkeran, Aspen Pharma; n = 41) and generic melphalan (Alkacel, Celon Labs, India; n = 55) formulations. All consecutive patients at a single center from the period 2011-2018 were included. RESULTS: The median follow-up in the innovator and generic groups was 61.7 and 32.5 months, respectively. Both groups were matched for age, sex, stage, and myeloma response. There were significantly more patients in the innovator melphalan group who were administered melphalan at a reduced dose at physician discretion (26.8% vs. 3.6%, p = .001). There were significantly more patients with grade 3 or higher mucositis (68.3% vs. 38.1%, p < .0001) and grade 3 or higher diarrhea (85.4% vs. 50.1%, p < .0001) in the innovator group. The median duration of hospital stay was significantly longer in the innovator group (19 days vs. 15.5 days, p < .0001). There were significantly more patients in the generic group who received standard maintenance (94.5% vs. 34.1%, p < .0001). Despite the differences in the melphalan dose and post-transplant strategies, the 4-year progression-free survival and overall survival were not significantly different in the two groups (58% vs. 63%, p = .7, 71% vs. 72%, p = .4, respectively). CONCLUSION: Long-term efficacy comparison is helpful in the absence of postmarketing bioequivalence studies of generic melphalan.

Rare Association of Leukocytoclastic Vasculitis in Visceral Leishmaniaisis.

A 30-year-old man presented with fever, hepatosplenomegaly, and a rash over his lower limbs (palpable purpura). Evaluation revealed pancytopenia and hypergammaglobulinemia. A subsequent bone marrow examination and serology confirmed visceral leishmaniasis (kala-azar), while the biopsy of skin lesion suggested leukocytoclastic vasculitis. No alternate cause of vasculitis was forthcoming, and the patient was treated with conventional amphotericin B for 14 days after which resolution of symptoms (including the rash) was noted. Cutaneous vasculitis is an extremely rare complication following visceral leishmaniasis with no known cases reported thus far. Hence, a high index of suspicion is warranted in achieving timely diagnosis and initiation of appropriate therapy.

High Prevalence of Celiac Disease in Patients with Immune Thrombocytopenia.

Celiac disease (CD) is known to be associated with several autoimmune disorders. We studied the prevalence of subclinical CD among patients with immune thrombocytopenia (ITP) as compared to general population. Cases of primary ITP between the age group of 18-60 years were studied. Besides clinical examination, all patients underwent serology testing for tissue transglutaminase antibody (tTG) IgA and anti-endomysial antibodies IgA. The diagnosis of CD was made if both antibodies were positive. Healthy subjects acted as controls and underwent serological testing for tTG IgA. Seventy-nine primary ITP and 316 healthy subjects underwent serology testing for CD. Four patients of primary ITP (4/79) were positive for both serology as compared to 2 (2/316) healthy controls [odds ratio 8.37 (CI 1.50-46.47, p < 0.005)]. Among the ITP cases only one had clinical symptoms of CD while none of the healthy controls had symptoms of CD. There is a significantly higher prevalence of subclinical CD in patients with ITP. Since the prevalence of CD is known to vary among different geographical zones, we suggest further studies on screening of ITP patients for CD in areas of high prevalence.

Immune Thrombocytopenia is Still the Commonest Diagnosis on Consultative Hematology.

Thrombocytopenia is often a source of concern for physicians and patients alike and is one of the commonest reasons for a hematology consultation. Through this study, we wish to ascertain the different etiologies which should be kept in mind by a hematologist when a consultation for thrombocytopenia is sought. We assessed the etiology & clinical features of thrombocytopenia seen on consultative hematology calls for patients admitted in the general ward of a tertiary care hospital. 88/277 hematology consultations taken over a course of 2 months were for thrombocytopenia. The median age of these patients was 30 years, 62.5% were female, and median platelet of 40,500/µL (1000-112000). Mild, moderate & severe thrombocytopenia was seen in 6.8%, 27.3% and 65.9% respectively. 50% of patients had a primary hematological diagnosis. Immune thrombocytopenia (ITP) was the commonest diagnosis (38.6%). Bleeding manifestations were present in 48.9% patients with 20.5% having a major bleed. One third of hematology consultations in the general ward and emergency of a tertiary care hospital are for thrombocytopenia. Almost in half, the etiology of thrombocytopenia is related to a primary hematological disorder. This information should help in decision making of use of appropriate resources.

Impact of frailty, melphalan pharmacokinetics, and pharmacogenetics on outcomes post autologous hematopoietic cell transplantation for multiple myeloma.

Autologous hematopoietic cell transplantation (auto-HCT) using melphalan is the standard of care in the management of myeloma. Auto-HCT is a safe procedure with tolerable toxicity except in Asian-Indians. We hypothesized either one or a combination of factors: (1) frailty (assessed by IMWG frailty score), (2) generic melphalan pharmacokinetic area under the curve (AUC) assessed by high-performance liquid chromatography, and (3) pharmacogenetics of glutathione S-transferase (GSTP1) assessed by Sanger sequencing, to be associated with toxicity and survival outcomes post auto-HCT. Disease response was evaluated by IMWG response criteria at day +100 post auto-HCT. Gastrointestinal (GI) toxicity, infections, hospital stay, progression-free survival (PFS) were also recorded. A total of 35 patients were evaluated over 2 years (2016-2018). Frailty, not HCT-comorbidity index correlated with GI toxicity and infections. Overall there was an 11-fold variation in melphalan AUC with a median of 27.88 mg h/L (10.06-110.26). Patients with AUC more than the median had more GI toxicity and infections. Patients with wild-type GSTP1 polymorphism had more GI toxicity and infections. Frailty, AUC, or GSTP1 polymorphism did not impact hospitalization duration or PFS. A combination of the factors frailty, melphalan pharmacokinetics, and pharmacogenetics impacts GI toxicity and infections after auto-HCT in myeloma.

Renal Dysfunction in Patients With Nonalcoholic Fatty Liver Disease is Related to the Presence of Diabetes Mellitus and Severity of Liver Disease.

BACKGROUND AND AIMS: There is sparse data on the prevalence of renal dysfunction in patients with nonalcoholic fatty liver disease (NAFLD). The aim of the present study was to evaluate the presence of renal dysfunction in patients with NAFLD and correlate it with the severity of liver disease. METHODS: One hundred nonalcoholic patients with ultrasound showing hepatic steatosis were enrolled into the study after exclusion of other causes. Presence of renal dysfunction was estimated by glomerular filtration rate and by evaluating 24 h urinary protein and microalbumin. Various risk factors including components of metabolic syndrome, severity of hepatic steatosis (as assessed on ultrasound), hepatic necro-inflammation (as assessed by hepatic transaminases) and hepatic fibrosis (as assessed by transient elastography) were correlated with the presence of renal dysfunction. RESULTS: Twenty eight (28%) patients with NAFLD had evidence of impaired renal function with 5 (5%) having abnormal glomerular filtration rate, 18 (18%) having significant proteinuria and 5 (5%) having both. Presence of type 2 diabetes mellitus, raised hepatic transaminases and advanced fibrosis on transient elastography were found as independent predictors of impaired renal function with raised hepatic transaminases having the best sensitivity (89%) and presence of advanced fibrosis the best specificity (90%). A model comprising of these three parameters had good accuracy (AUROC = 0.763) in predicting impaired renal function in patients with NAFLD. CONCLUSIONS: Around one-third of patients with NAFLD have impaired renal functions. Prevalence of impaired renal function in patients with NAFLD is dependent on the severity of liver disease and presence of diabetes mellitus.

Cutaneous herald: leukaemia cutis as presenting manifestation of relapse in acute promyelocytic leukaemia.

Leukaemia cutis or cutaneous infiltration of neoplastic myeloid or lymphoid cells is usually seen in the acute myelomonocytic and acute monocytic variants of acute myeloid leukaemia. Here, we report a case of acute promyelocytic leukaemia who achieved remission, presenting with skin lesions, the biopsy of which revealed leukaemia cutis, heralding the relapse of the disease. After establishing the diagnosis with bone marrow analysis, the patient was started on daunorubicin chemotherapy along with arsenic trioxide and all-trans retinoic acid. Afterwards, the skin lesions resolved, and the patient is planned for consolidation with bone marrow transplantation.

A quintessential syndrome with a rare marvelling aetiology: Rosai-Dorfman disease presenting as Conus-Cauda syndrome.

A 19-year-old woman presented with a history of severe lower backache and asymmetric proximal lower limb weakness during the past 3 months. In addition, she also suffered from lower motor neuron-type bladder and bowel symptoms. On examination, paraparesis was noted. Further, sensory examination suggested patchy asymmetric sensory loss in both lower limbs with saddle anaesthesia and areflexia. A clinical diagnosis of Conus-Cauda syndrome was made and contrast-enhanced MRI of the lumbar and sacral spine was done, which confirmed the presence of a mass lesion within the spinal canal involving the cauda equina extending up to the sacral level. She underwent partial resection of the lesion following which the neurological deficits and lower backache resolved. Histopathological evaluation and immunohistochemical analyses uncovered Rosai-Dorfman disease. There was no evidence of disease elsewhere in the body. Since the patient improved significantly following surgery and exhibited no further neurological worsening, she remains under close follow-up.

Elevated cardiac biomarkers and echocardiographic left ventricular dysfunction at admission in patients with dengue fever: report from a tertiary care center in Northwest India.

Cardiac involvement is not an uncommon manifestation in dengue fever and diagnosing it has always been a challenge to physicians owing to its constellation of clinical features and lack of standard screening methods. We studied the prevalence of cardiac involvement among fifty sequential adult patients of dengue fever admitted in our emergency department, PGIMER, Chandigarh, India, who were assessed clinically and classified based on the severity. They were studied for possible cardiac involvement by means of point-of-care testing for serum cardiac biomarkers (quantitative troponin-I, creatinine kinase - MB Isoform and cardiac myoglobin) and two-dimensional transthoracic echocardiogram (2D-echo). Evidence of myocardial involvement was present in 16% and 30% patients based on 2D-echo and biomarker testing respectively. On univariate analysis, the presence of cardiac symptoms (p = 0.009) and of shock (p = 0.003) showed statistically significant association with biomarker elevation. However, this and evidence of myocardial dysfunction by 2-D echo showed poor inter-correlation.

Lung consolidation responding to chemotherapy.

Consolidations in the pulmonary parenchyma are mostly infective, although they can rarely be due to autoimmune and neoplastic processes. Consolidations, especially in the setting of underlying immunosuppressive haematological malignancy, are usually presumed infective by the treating physician. Pulmonary involvement in chronic lymphocytic leukaemia presenting as consolidations and type 1 respiratory failure, responding to systemic chemotherapy, is a rare and uncommon presentation.