Multicenter Outcome of Hematopoietic Stem Cell Transplantation for Primary Immune Deficiency Disorders in India.

Background: Hematopoietic stem cell transplantation (HSCT) is the curative option for many primary immune deficiency disorders (PID). In the last 5 years, increased awareness, availability of diagnostics based on flow cytometry, genetic testing, improved supportive care, use of reduced toxicity conditioning, and success of haploidentical donor HSCT have improved access to HSCT for children with PID in India. We present results on children with PID who underwent HSCT across India and the factors that influenced outcome. Patients and Methods: We collected retrospective data on the outcome of HSCT for PID from seven centers. We analyzed the impact of the type of PID, conditioning regimen, time period of HSCT- before or after January 2016, graft versus host disease prophylaxis, cause of mortality and overall survival. Results: A total of 228 children underwent HSCT for PID at a median age of 12 months (range, 1 to 220 months) with a median follow up of 14.4 months. Infants accounted for 51.3% of the cohort and the male female ratio was 3:1. SCID (25%) and HLH (25%) were the more frequent diagnoses. Matched family donor was available in 36.4% and 44.3% children had a haploidentical HSCT. Reduced and myeloablative conditioning regimens were used with 64% children receiving a treosulfan based conditioning regimen. Peripheral blood stem cells were the predominant graft source at 69.3%. The survival in infants (60.2%) was inferior to children aged over 1 year (75.7% p value = 0.01). Children with Wiskott Aldrich syndrome (74.3%) and chronic granulomatous disease (82.6%) had the best outcomes. The survival was superior in children receiving HSCT from a matched sibling (78%) versus an alternate donor HSCT (61% p value = 0.04). In the cohort transplanted after January 2016 survival improved from 26.8% to 77.5% (p value = 0.00). Infection remains the main cause of mortality at in over 50% children. The 5-year overall survival rate was 68%. Conclusion: Survival of children with PID undergoing HSCT in India has improved dramatically in last 5 years. Alternate donor HSCT is now feasible and has made a therapeutic option accessible to all children with PID.

Disseminated intravascular coagulation in acute leukemia at presentation and during induction therapy.

Between January 2001 and December 2003, 67 patients with acute leukemia were evaluated prospectively for hemostatic abnormality at presentation, of which 43 (64.2%) had acute lymphoblastic leukemia and 24 (35.8%) had acute myelogenous leukemia. At presentation, 27 patients (40.3%) had bleeding manifestations. Thrombocytopenia was present in 57 patients (85%), and 33(49.3%) had some abnormality of global coagulation markers. Disseminated intravascular coagulation was defined by International Society of Thrombosis and Hemostasis criteria. Disseminated intravascular coagulation was more often associated with bleeding manifestations in acute myelogenous leukemia cases than in acute lymphoblastic leukemia cases. Two patients presented disseminated intravascular coagulation on day 7 of chemotherapy, without any bleeding manifestations. Four of 15 evaluated cases who had a bleeding or infection complication after day 7 of induction therapy also had disseminated intravascular coagulation. It is recommended that all patients with leukemia be investigated for disseminated intravascular coagulation at presentation.

Molecular characterization of thalassemia intermedia in Indians.

Thalassemia intermedia shows considerable heterogeneity. The purpose of this study was to evaluate the prevalence and effect of common molecular determinants in thalassemia intermedia. In 73 cases of thalassemia intermedia, the possible molecular basis was co-existent a-deletions (n=16/50), homozygous XmnI polymorphism (n=17/50), both factors (n=3/50), and milder beta-alleles (n=9/50) in homozygous beta-thalassemia (total 50 cases). In heterozygous beta-thalassemia, alphaalphaalphaanti-3.7 triplication was the predominant factor (14/23 cases).

Hydroxyurea in thalassemia intermedia--a promising therapy.

Pharmacological agents such as hydroxyurea (HU) have been known to cause induction of fetal hemoglobin and possibly may alleviate the symptoms in thalassemia intermedia patients. Thirty-seven patients with beta-thalassemia intermedia were enrolled to assess response to HU therapy. Major response was defined as transfusion independence or hemoglobin rise of more than 20 g/l and minor response as rise in hemoglobin of 10-20 g/l or reduction in transfusion frequency by 50%. The median age was 10 years (range: 4-50 years) and median follow-up was 12 months (range: 4-36 months). Twenty-six patients (70.2%) showed response to HU therapy. Seventeen patients (45.9%) were major responders, and nine patients (24.3%) showed minor response. There was no correlation of response with beta-thalassemia mutation or XmnI polymorphism; however, the presence of alpha(3.7) deletion was associated with major response in three patients. Mean fetal hemoglobin (HbF) levels rose on HU therapy. Older age, low baseline F cell percent, and low baseline HbF levels (below 10%) were predictors of poor response. Response was evident within 1 month of starting HU therapy in the majority of responders. Thus, a short trial of HU therapy can predict durable response.