Navin Khattry

Subcutaneous mycosis and fungemia by Aureobasidium pullulans : a rare pathogenic fungus in a post allogeneic BM transplant patient

Subcutaneous mycosis and fungemia by Aureobasidium pullulans : a rare pathogenic fungus in a post allogeneic BM transplant patient

Comparison of the efficacy and safety of Rituximab (Mabthera™) and its biosimilar (Reditux™) in diffuse large B-cell lymphoma patients treated with chemo-immunotherapy: A retrospective analysis

Background: Rituximab (Mabthera™) have been in use in India since 2000. A biosimilar molecule of rituximab (Reditux™) was approved in India in 2007. This retrospective audit was done to compare the efficacy and safety of Mabthera™ with Reditux™. Materials and Methods: We reviewed the charts of 223 adult diffuse large B-cell lymphoma patients who had received cyclophosphamide, doxorubicin, vincristine and prednisolone with rituximab chemotherapy. Tumor recurrence, survival and toxicities experienced during chemotherapy were obtained from the patient charts. The survival analysis was restricted to patients who received at least 4 cycles of the same brand. Results: Of the 223 patients evaluated, 101 received Mabthera™, 72 received Reditux™. There were no differences in the infusional reaction rates, grades 3 and 4 neutropenia and oral mucositis between the two brands. Complete-remission (CR) rates were similar with Mabthera™ and Reditux™ (75% and 82%, respectively; P = 0.294). The progression free survival (PFS) rate at 5 years were 72% in Mabthera™ and 81% in Reditux™ (P = 0.382). The overall survival (OS) at 5 years were comparable in the two groups (66% in Mabthera™ and 76% in Reditux™; P = 0.264). Conclusion: We observed no significant differences in the toxicity, tumor response rates, PFS and OS between the two available brands of rituximab.

Severe weight loss in 3 months after allogeneic hematopoietic SCT was associated with an increased risk of subsequent non-relapse mortality

Patients after allogeneic hematopoietic SCT (HSCT) are at risk of malnutrition. To assess the impact of malnutrition after allogeneic HSCT on transplant outcomes, we conducted a retrospective study. Adult patients who received allogeneic HSCT from 2000 to 2009 for standard-risk leukemia and achieved disease-free survival up to 3 months after allogeneic HSCT were included. From participating centers, 145 patients were enrolled. Median age was 46 years (19–68). Patients were classified based on weight loss during 3 months after allogeneic HSCT as follows: normal group (weight loss <5%, n=53), mild malnutrition group (5%⩽weight loss<10%, n=47), severe malnutrition group (10% ⩽weight loss, n=45). The cumulative incidences of 2-year nonrelapse mortality (NRM) were 3.8% in the normal group, 8.5% in the mild malnutrition group and 27.3% in the severe malnutrition group. The probabilities of a 2-year OS were 73.2% in the normal group, 74.5% in the mild malnutrition group and 55.3% in the severe malnutrition group. In multivariate analysis, severe malnutrition was associated with an increased risk of NRM and a worse OS. In conclusion, weight loss ⩾10% was associated with a worse clinical outcome. Prospective studies that identify patients at risk of malnutrition and intervention by a nutritional support team are warranted.

HLA match likelihoods for Indian patients seeking unrelated donor transplantation grafts: a population-based study

BACKGROUND For patients who do not have a suitable human leukocyte antigen (HLA)-matched family donor, unrelated donor registries of adult volunteers and banked umbilical cord blood (UCB) units provide the potential for successful haemopoietic stem-cell transplantation. The size and genetic composition of such registries determines the proportion of patients who will be able to find a suitable match. We aimed to assess the proportion of positive matches for Indian patients. METHODS Using HLA data from ten existing donor and UCB registries and clinical transplant centres in India, we built population-based genetic models for 14 Indian regions to model Indian registry growth to predict the likelihood of identifying a suitable donor-either an adult donor or UCB-for Indian patients. We computed ranking tables of the top ten haplotypes in each regional group and compared these with four US samples from the National Marrow Donor Program (NMDP) registry. FINDINGS The mean proportion of individuals who would have a 10/10 adult donor match within India ranged from 14·4% with a registry size of 25 000 to 60·6% with a registry size of 1 000 000. Only when donor registries increased to 250 000 did the match rate within India exceed that found by searching the US-NMDP registry combined with an Indian registry of 25 000 donors. The proportion of matches increased logarithmically with increased registry size (R(2)=0·993). For a UCB registry size of 25 000, 96·4% of individuals would find a 4/6 match; however, only 18·3% would have a 6/6 match. INTERPRETATION Serial match modelling and follow-up comparisons can identify the relative and progressively greater value of an India-based donor registry and UCB banking network to serve the Indian population. Understanding regional HLA haplotype diversity could guide registry growth and maximise benefit to patients. Similar modelling could guide planning for the needs of other ethnically distinct populations. FUNDING University of Minnesota and the Indian Council for Medical Research.

Hepatitis B-related serological events in hematopoietic stem cell transplant patients and efficacy of lamivudine prophylaxis against reactivation

Reactivation of remote hepatitis B infection (RHBI) is an important cause of morbidity in hematopoietic cell transplant (HCT) patients. We analyzed the prevalence of RHBI in 205 patients who underwent HCT in our centre, serological events related to hepatitis B virus (HBV) reactivation and role of lamivudine prophylaxis in HCT patients with RHBI. The prevalence of RHBI was 14% (28/205 patients). Of these 28 patients, 15 received lamivudine prophylaxis (14 anti‐HBcIgG positive and 1 only anti‐HBs positive) while 13 did not receive lamivudine prophylaxis (12 anti‐HBs positive and 1 anti‐HBcIgG positive). None in prophylaxis group developed HBV reactivation while 12 of 13 in no‐prophylaxis group reactivated (P < 0.001). The rate of HBV reactivation was 10% (21/205 patients), which included 9 patients with no evidence of RHBI pre‐transplant. We conclude that lamivudine prophylaxis protects against HBV reactivation in HCT patients with evidence of RHBI. Lamivudine prophylaxis should be used not only in patients with anti‐HBcIgG positivity but also in those with isolated anti‐HBs positivity pre‐transplant given the high rate of HBV reactivation in these patients. HBV serology cannot identify all cases with RHBI and therefore does not preclude HBV reactivation post‐transplant. Copyright

Consensus in the Management of Multiple Myeloma in India at Myeloma State of the Art 2016 Conference.

The science of multiple myeloma (MM) and related plasma cell disorders is rapidly evolving with increased understanding of the disease biology and recent approval of the newer drugs widening the therapeutic armamentarium. Despite multiple international guidelines regarding the management of this disease, the practice of managing MM is not uniform amongst Indian physicians. There are challenges in management which are unique to the Indian patients. This review discusses these challenges and the consensus of the nation-wide experts in dealing with the same. We also briefly highlighted the perspective of international experts as discussed in the Myeloma State of the Art conference held in September 2016 at PGI, Chandigarh. An Indian Myeloma Academic Groupe (IMAGe) group was formed to strengthen the research, create awareness about myeloma and related disorders and form consensus guidelines/ recommendations that can be adapted to the Indian Scenario.

Parenthood in patients with acute promyelocytic leukemia after treatment with arsenic trioxide: a case series

Abstract Arsenic trioxide, believed to be a carcinogen and a teratogen, has found its niche in the treatment of acute promyelocytic leukemia (APL). APL is a disease affecting young patients. Post-treatment fertility and outcome of pregnancy are always a concern in a disease with high cure rates. We report a case series of six patients who were treated successfully for APL with arsenic trioxide and who parented at least one healthy offspring after completing their treatment.

Characteristics of BCR-ABL kinase domain mutations in chronic myeloid leukemia from India: not just missense mutations but insertions and deletions are also associated with TKI resistance

Abstract We document the characteristics of BCR-ABL kinase domain mutations (KDM) in the largest study from India comprising of 385 patients and demonstrate that more than half (51.9%) of these patients have detectable abnormalities in the KD both in adult and in pediatric chronic myelogenous leukemia (CML). These comprise singly occurring missense mutations (25.5%), polyclonal/compound point mutations (4.9%), and insertions/deletions (29.6%). Missense mutations were most commonly seen in the imatinib-binding region followed by the P-loop. The commonest mutation in our dataset was T315I. Other common missense mutations were Y253H, M244V, and F317L. A high prevalence of BCR-ABL exon7 deletion (p.R362fs*) was also seen (25.5% of the entire cohort), whereas the 35bpintron-derived insertion/truncation mutation detected in 12 patients. In the pediatric age group, 58.8% of patients harbored missense mutations, polyclonal/compound mutations as well as insertions and deletions. We detected 11 novel mutations (seven missense mutations and four insertions/deletions).

Doxorubicin-induced cardiotoxicity in adult Indian patients on chemotherapy

Background: Doxorubicin-induced cardiotoxicity is widely known to occur at cumulative doses exceeding 450 mg/m2. However, very few studies have reported incidence of cardiac dysfunction in patients on chemotherapy with lower cumulative doses. To the best of our knowledge, there is no study carried out so far that has reported the incidence of cardiac dysfunction in adult Indian patients receiving doxorubicin. This study was undertaken to determine the incidence of doxorubicin-induced cardiotoxicity by serial resting echocardiography in patients on chemotherapy and identify risk factors associated with cardiotoxicity. Materials and Methods: Patients that were started on doxorubicin-based chemotherapy in the period from January 2000 to June 2001 and had completed at least 300 mg/m2 cumulative dose were taken in the study. Electrocardiography, chest X-ray and echocardiography were done at baseline, at 300 mg/m2 and at 450 mg/m2 cumulative doses of doxorubicin. All patients were evaluated for the presence of the following risk factors: Age>70 years, female sex, preexisting cardiac disease, hypertension, chest wall irradiation, body mass index (BMI)<20 kg/m2 , Karnofsky performance status, combination chemotherapy with cyclophosphamide and presence of liver disease. Subclinical cardiac dysfunction was defined as ejection fraction fall greater than 10% on follow-up echocardiography. Results: Thirty patients satisfied the criterion for being considered for evaluation. One (3%) patient developed congestive cardiac failure, while 8 (27%) patients developed subclinical cardiac dysfunction. Concomitant use of cyclophosphamide significantly increased the risk of cardiac dysfunction (P = 0.048), while low BMI (<20 kg/m2) and preexisting cardiac disease showed a trend towards increased risk of cardiac dysfunction (P = 0.07 for both). Conclusion: Twenty-seven percent of the patients developed subclinical cardiac dysfunction in the cumulative dose range of 300-450 mg/m2 . This entails regular monitoring for cardiac dysfunction by echocardiography during treatment.

Cryptococcus laurentii diarrhea post hematopoietic stem cell transplant

We report the recent isolation of Cryptococcus laurentii from the feces of a patient with Hodgkins lymphoma who underwent autologous hematopoietic stem cell transplant (HSCT). The organism was identified using microscopic morphology, cultural characteristics, and biochemical tests including sugar assimilation. Minimum inhibitory concentration of various antifungals was determined by microbroth dilution method. The recovery of pure culture of C. laurentii from stool culture, and the patients response to treatment with voriconazole support its potential etiological role. To the best of our knowledge, we report the first case of diarrhea caused by C. laurentii in an HSCT recipient.