Gaurav Kharya

Langerhans cell histiocytosis with digestive tract involvement

Gastrointestinal tract (GIT) involvement in Langerhans cell histiocytosis (LCH) is not commonly described. We present two children presenting with GIT involvement with LCH, one successfully treated on standard protocol and other being treated on a protocol for relapsed disease. A review of literature showed almost 95% children were less than 2 years of age and 62% were females. Vomiting, abdominal pain, constipation, intractable diarrhea, malabsorption, bloody stools, protein‐losing enteropathy, and even intestinal perforation are some of the reported symptoms. More than 50% patients died within 18 months from diagnosis. Pediatr Blood Cancer. 2010;55:748–753.

Management of severe refractory thrombocytopenia in dengue hemorrhagic fever with intravenous anti-D immune globulin.

Dengue hemorrhagic fever (DHF) is a potentially lethal complication of dengue fever due to shock and/or bleeding. Bleeding in DHF is due to thrombocytopenia and/or coagulopathy. The authors present their experience of usage of intravenous anti-D in 5 children with DHF and severe refractory thrombocytopenia (<10,000/mm3). It was administered in a dose of 50 to 75 μg/kg. Mean platelet count was 6800/mm3 before and 33,600, 44,600, and 79,000/mm3 after intravenous anti-D administration at 24, 48, and 72 hours, respectively. Average drop in hemoglobin after administration of anti-D was 2.28 g/dL. Intravenous anti-D can possibly be a treatment option for refractory thrombocytopenia in DHF.

Control of massive bleeding in dengue hemorrhagic fever with severe thrombocytopenia by use of intravenous anti-D globulin.

Dengue hemorrhagic fever (DHF) is a potentially lethal complication of mosquito borne viral disease, Dengue Fever. Thrombocytopenia is a constant finding in DHF/Dengue Shock Syndrome (DSS). We report two cases that fulfilled the WHO criteria of DSS: high fever, positive tourniquet test, severe thrombocytopenia (<10,000/mm3), hemo‐concentration (Hematocrit increase >20%), hypotension and bleeding refractory to routine therapeutic measures, who showed dramatic improvement after receiving Intravenous Anti‐D globulin (IV anti‐D). Pediatr Blood Cancer 2008;51:812–813.

Barriers to Cure for Children with Cancer in India and Strategies to Improve Outcomes: A Report by the Indian Pediatric Hematology Oncology Group

The survival of children with cancer in India is inferior to that of children in high-income countries. The Indian Pediatric Hematology Oncology Group (IPHOG) held a series of online meetings via www.Cure4kids.org to identify barriers to cure and develop strategies to improve outcomes. Five major hurdles were identified: delayed diagnosis, abandonment, sepsis, lack of co-operative groups, and relapse. Development of regional networks like IPHOG has allowed rapid identification of local causes of treatment failure for children with cancer in India and identification of strategies likely to improve care and outcomes in the participating centers. Next steps will include interventions to raise community awareness of childhood cancer, promote early diagnosis and referral, and reduce abandonment and toxic death at each center. Starting of fellowship programs in pediatric hemato-oncology, short training programs for pediatricians, publishing outcome data, formation of parent and patient support groups, choosing the right and effective treatment protocol, and setting up of bone marrow transplant services are some of the effective steps taken in the last decade, which needs to be supported further.

Comparison of Amicus and COBE Spectra for allogenic peripheral blood stem cell harvest: Study from tertiary care centre in India

INTRODUCTION Most common source of stem cell graft for both autologous and allogenic haematopoietic transplants are peripheral blood haematopoietic progenitor stem cells. Adequate collection of the CD34+ cells and safety of the allogenic donor during the leukapheresis are of prime importance to an apheresis physician. Our retrospective analysis is a comparison between of two platforms namely, COBE Spectra and Amicus, for CD34+ mononuclear cell collection. MATERIAL AND METHOD The study included the data of GSCF (Granulocyte-Colony-Stimulating Factor) mobilized allogenic PBSC collections at our centre from January 2015 to June 2016. The apheresis platforms used were COBE Spectra and Amicus. Blood cell counts were done using LH750 Beckman Coulter (Florida, Miami, USA). CD45+ & CD34+ cell counts were done using BD FACS Canto-II Flow-Cytometer by ISHAGE guidelines. RESULTS A total of 170 PBSC (100 COBE Spectra & 70 Amicus) harvests were done on 143 donors, of which 116 completed the collection in a single session and 27 required a second session. Demographic details and pre harvest peripheral blood counts for both the groups did not show any statistical differences. Amicus processed higher blood volume with higher ACD exposure and procedure time compared to COBE Spectra. Higher platelets loss was with COBE Spectra harvests with higher product volumes collection. Collection efficiency (CE2), collection ratio, CD34+ cells dose was similar on both the platforms. RBC contamination, absolute lymphocyte and monocytes counts were significantly higher with Amicus harvest product compared with COBE Spectra. A total of 14 (8.2%; citrate toxicity) adverse reactions were reported out of 170 allogenic PBSC collections. DISCUSSION/CONCLUSION Our study suggests that both Amicus and COBE Spectra platforms offer comparable results for allogenic PBSC collections. Amicus offers a concentrated PBSC product with lesser volume and platelets loss but higher RBC contamination.

Hematopoietic Stem Cell Transplant in Elderly Patients: Experience from a Tertiary Care Centre in Northern India

One-fifth of the world’s population resides in India. The burden of hematological diseases both malignant and nonmalignant is huge in the country. According to the registry data the total number of leukemia and lymphoma patients living in India in 2010 was about 100,000 [1]. The estimated size of the elderly population in India is expected to rise from 77 million in 2001 to 140 million by 2021. With the increasing awareness about hematological diseases and the rising economy, many patients are opting for hematopoietic stem cell transplant (HSCT) as a definite treatment for many hematological diseases. The role of HSCT for various hematological diseases in young patients is well established. Older patients have traditionally been considered ineligible for stem cell transplantation and data of HSCT in elderly is scarce, particularly from developing countries. Here we report our experience with stem cell transplantation in the elderly population in India. We reviewed the transplant database at Bone Marrow Transplant (BMT) centre, BLK Superspeciality Hospital, New Delhi. The conditioning regimen for allogeneic HSCT was reduced intensity conditioning (with fludarabine 30 mg/m for 5 days and melphalan 140 mg/m for 1 day). For autologous HSCT for multiple myeloma and lymphoma, melphalan 200 mg/m and BEAM regimens (BCNU 300 mg/m, etoposide 200 mg/m, cytarabine 200 mg/m and melphalan 200 mg/m) respectively were used as conditioning regimens. The transplants were performed in High Efficiency Particulate Air (HEPA) filtered rooms. Peripheral blood stem cell harvest was done after granulocyte-colony stimulating factor (G-CSF) mobilization. Graft versus host disease (GVHD) prophylaxis for allogeneic HSCT included cyclosporine and methotrexate. Patients received standard anti-viral prophylaxis with acyclovir and Pneumocystis jiroveci prophylaxis with trimethoprim-sulfamethoxazole. Patients were treated with broad spectrum antibiotics at the time of their first neutropenic fever, and with antifungal agents as per institutional policy. The study was approved by the Institutional Review Board. Out of 440 patients who underwent HSCT at BLK Superspeciality hospital from Feburary 2010 to August 2015, 19 (4.32 %) were C60 years of age. Median age was 63 years (range 60–73 years). There were 14 males and 5 females. Seven patients underwent allogeneic HSCT and 12 patients underwent autologous HSCT. All patients had normal liver and kidney functions and normal left ventricular ejection functions prior to HSCT. Six patients had diabetes well controlled with oral hypoglycemic agents. All allogeneic HSCTs were sibling matched peripheral blood stem cell transplantations. The most common indications for allogeneic and autologous HSCT were acute myeloid leukemia (AML) and multiple myeloma (MM) respectively (Table 1). The donors for allogeneic HSCT were females in five cases and males in two cases with a median age of 56 years (range 51–62 years). The median CD34? stem cell dose was 3.7 9 10/kg recipient body weight (range 1.88–8.77 9 10/kg). Neutrophil engraftment occurred at a median of 11 days (range 9–13 days) and platelet engraftment at 15 days (range 11–26 days). None of the patients had cytomegalovirus (CMV) reactivation. One patient developed grade 2 acute gut GVHD and three patients had limited chronic skin GVHD. Twelve patients & Sanjeev Kumar Sharma sksanjeev13@yahoo.com

Hemophagocytic Lymphohistiocytosis in Infants: A Single Center Experience from India

There is paucity of outcome data for hemophagocytic lymphohistiocytosis (HLH) in infants from India, especially post stem cell transplant (SCT). We report outcome data of eight infants diagnosed with HLH. Mean age was 7.1 months (range 2–11). Mutation analysis was possible in seven patients. One patient had Griscelli syndrome. In three patients, no known mutation could be identified, while in remaining three homozygous mutations in Perforin, Munc and STX11 gene were identified. All were treated as per HLH 2004 protocol. Four died during induction phase. One patient abandoned therapy. Two underwent SCT, while one is awaiting SCT. First patient is alive and disease-free at 22 months postmatched sibling donor SCT. Second underwent unrelated double cord blood transplant, but died 5 months posttransplant due to renal failure. It is feasible to offer SCT for infants with familial HLH in the developing world although barriers like sepsis and disease refractoriness remain.

Common Gamma chain- and JAK3-deficient SCID, conditioned versus unconditioned transplant: a single centre experience

Introduction: Initial trough Cyclosporine A (CsA) blood level can infl uence incidence of GVHD and relapse in patients with acute leukemia. We sought to evaluate the impact of initial CsA level (CSA-1) on the incidence of acute and chronic GVHD, relapse and survival and also explore factors that may aff ect CSA-1. Materials (or patients) and Methods: All patients who underwent allogeneic stem cell transplant (ASCT) for acute leukemia from January 2008 to March 2013 were included in this retrospective study. GVHD prophylaxis used was CsA (starting dose 1.5 mg/kg twice daily) from day -1 in combination with either methotrexate (MTX) or mycophenolate mofetil (MMF). CSA-1 was measured on day 4 or day 5 of starting CsA. Dose of CsA was modifi ed depending on CSA-1 to achieve therapeutic level of 150-200 ng/ml. For analysis, patients were divided into three groups based on modifi cation of CsA dose Group A (dose escalated), Group B (dose de-escalated) and Group C (dose unchanged). Comparisons were done between 3 groups for baseline characteristics, incidence of acute and chronic GVHD, incidence of relapse, transplant related mortality (TRM), relapse free survival (RFS) and overall survival (OS). Comparison between 3 groups was done by using chi-square test and survival outcomes by Kaplan Meier method. Multivariate analysis to determine factors predicting CsA dose escalation or de-escalation was done using logistic regression. Results: Seventy-four patients underwent 77 transplants; AML52, ALL-23, biphenotypic-2; 42 in CR1, 20 in CR2, 15 in relapsed/ refractory state; 65 from matched related, 10 from matched unrelated and 2 from haploidentical donors. Source of stem cells was peripheral blood in 70, bone marrow in 5 and cord blood in 2 transplants. The median age was 30 years (range 6-51). Conditioning regimen was full intensity (FI) i.e. TBI-Cy or Bu-Cy in 42 and reduced intensity (RI) i.e. fl udarabine based in 35 transplants. Total body irradiation (TBI) was used in 32 patients. GVHD prophylaxis was CsA+MTX in 53 and CsA+MMF in 24 patients. There were 27 patients in group A, 13 in group B and 37 in group C. On univariate analysis, use of FI regimen, cyclophosphamide and TBI; and Body Mass Index (BMI) <22 kg/m2 were associated with lower CSA-1 while use of fl udarabine, RI regimen and BMI>22 kg/m2 were associated with higher CSA-1. On multivariate analysis, fl udarabine use and BMI>22 kg/m2 predicted for higher CSA-1 requiring CsA dose de-escalation (P=0.038 and 0.034 respectively). Incidence of all grade and grade II-IV acute GVHD was 48% and 11% in group A, 38% and 31% in group B, and 43% and 19% in group C respectively (P= NS). Incidence of chronic GVHD was 52% in group A, 38% in group B and 57% in group C (P=NS). Incidence of relapse was 41% in group A, 23% in group B and 32% in group C (P= NS). TRM was 7% in group A, 38% in group B and 11% in group C (P= NS). OS and RFS at 4 years was 33% and 29% in group A, 43% and 46% in group B, and 53% and 45% in group C respectively (P=NS). Discussion: BMI <22 kg/m2 is associated with lower CSA-1 requiring CsA dose escalation. Use of fl udarabine based conditioning and BMI>22 kg/m2 is associated with higher CSA-1 requiring CsA dose de-escalation. Transplant outcomes including rates of acute and chronic GVHD, TRM, relapse incidence and overall survival are not signifi cantly aff ected by initial CsA level. Disclosure of Interest: None Declared.