Sachin Punatar

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

A case of reversible dilated cardiomyopathy due to acromegaly with partial empty sella

Acromegaly has several cardiovascular manifestations of which cardiomyopathy (CMP) and hypertension (HTN) are important and contribute to the increased mortality associated with the disease. Both these manifestations are reversible with treatment. However, very advanced CMP with severe systolic dysfunction has low likelihood of reversal. The reversibility is higher in young population and decreases as age advances. Also, the time required for these manifestations to resolve is about 1 year. Here, we describe a case in which HTN and advanced heart failure resolved in an aged patient within a very short span of 2 months from the time of presentation.

Is long term storage of cryopreserved stem cells for hematopoietic stem cell transplantation a worthwhile exercise in developing countries

Background Stem cell units (SCUs) that are cryopreserved prior to both autologous and allogeneic hematopoietic stem cell transplants (for donor lymphocyte infusion) remain unused or partially used several times, and become an increased burden to blood banks/SCU repositories. Because of the scarcity of data regarding the duration for which the storage is useful, there is no general consensus regarding disposal of SCUs. Methods We conducted a retrospective audit of SCU utilization in 435 patients who planned to undergo either autologous stem cell transplantation (auto-SCT) (N=239) or allogeneic stem cell transplantation (allo-SCT) (N=196) at a tertiary cancer care center between November 2007 to January 2015. Results Our cohort consisted of 1,728 SCUs stored for conducting auto-SCT and 729 SCUs stored for conducting donor lymphocyte infusions (DLIs) after allo-SCT. Stem cells were not infused in 12.5% of patients who had planned to undergo auto-SCT, and 80% of patients who underwent allo-SCT never received DLI. Forty-one percent of SCUs intended for use in auto-SCT remained unutilized, with a second auto-SCT being performed only in 4 patients. Ninety-four percent of SCUs intended for carrying out DLIs remained unused, with only minimal usage observed one year after undergoing allo-SCT. Conclusion The duration of storage of unused SCUs needs to be debated upon, so that a consensus can be reached regarding the ethical disposal of SCU.

Thyroid cancer in Gardner's syndrome: Case report and review of literature

Gardner’s syndrome is a variant of familial adenomatous polyposis. A multitude of extra-colonic manifestations including various endocrine tumors have been associated with this syndrome, the commonest of which is thyroid cancer. Majority of the patients with thyroid cancer and Gardner’s syndrome are females. Here we describe a male patient with Gardner’s syndrome who subsequently developed thyroid cancer.

Nomogram to predict the presence of EGFR activating mutation in lung adenocarcinoma

To the Editors: Girard et al. [1] developed a nomogram to predict the presence of epidermal growth factor receptor ( EGFR ) activating mutations. Before using it in practice, however, the precision and limitations must be considered. Patient selection for tyrosine kinase inhibitors (TKIs) based exclusively on EGFR mutations is still controversial, because clinical response rates to TKI are nearly 70% in tumours harbouring EGFR activating mutations. Other factors, such as amplification of the EGFR gene and the activity of molecules downstream of EGFR, such as phosphorylated protein kinase B, and mutations of KRAS …

Antibiotic Lock Therapy for Salvage of Tunneled Central Venous Catheters with Catheter Colonization and Catheter-Related Bloodstream Infection

Central venous catheters (CVCs) represent a significant source of infection in patients undergoing hematopoietic stem cell transplantation and can add to the cost of care, morbidity, and mortality. Organisms forming biofilms on the inner surface of catheters require a much higher local antibiotic concentration to clear the pathogen growth. Antibiotic lock therapy (ALT) represents one such strategy to achieve such high intraluminal concentrations of antibiotics and can facilitate catheter salvage. Patients with catheter colonization (CC) or hemodynamically stable catheter‐related bloodstream infection (CRBSI) received ALT per institutional policy. We analyzed the incidence of CC and CRBSI and salvage rate of tunneled CVCs (Hickman) with ALT in patients undergoing hematopoietic stem cell transplant in this retrospective study. Catheter colonization was noted in 9.8% and CRBSI in 10.7% patients. Gram‐negative bacilli (GNB) accounted for 45% and 83% of isolates in CC and CRBSI, respectively. In patients with CRBSI, the rate of catheter salvage with the use of ALT in addition to systemic antibiotics was 86% compared to 55% in patients with systemic antibiotics use only (P = 0.06). There was no CRBSI related mortality, and no increase in resistant strains was noted at subsequent CRBSI. In conclusion, ALT represents an important strategy for catheter salvage, especially for gram‐negative infections, in a carefully selected patient population.

Lomustine, cytarabine, cyclophosphamide, etoposide – An effective conditioning regimen in autologous hematopoietic stem cell transplant for primary refractory or relapsed lymphoma: Analysis of toxicity, long-term outcome, and prognostic factors

Background: High-dose chemotherapy followed by autologous hematopoietic stem cell transplant (HSCT) is the treatment of choice for patients with relapsed and refractory (RR) lymphoma. We analyzed toxicity and long-term outcome with lomustine, cytarabine, cyclophosphamide, etoposide (LACE) conditioning in patients with primary refractory or relapsed lymphoma undergoing autologous transplant. Materials and Methods: One-hundred patients with primary refractory (23), chemotherapy sensitive relapse (74) or RR (3) Hodgkin lymphoma (HL - 70 patients), and non-HL (NHL - 30 patients) underwent HSCT with LACE (lomustine 200 mg/m 2 day-7, etoposide 1000 mg/m 2 day-7, cytarabine 2000 mg/m 2 day-6 to day-5, and cyclophosphamide 1800 mg/m 2 day-4 to day-2) conditioning between November 2007 and December 2013. At transplant, 68 patients were in complete remission (CR), 29 in partial remission, 2 had stable disease, and 1 had progressive disease. Patients were followed up for development of transplant-related toxicities and long-term survival outcome. Results: The incidence of grades 3–4 oral mucositis and grades 3–4 diarrhea was 8% and 4%, respectively. Median days to myeloid and platelet engraftment were 10 and 13. Transplant-related mortality was 7%. At median follow-up of 3 years, probability of overall survival (OS) and progression-free survival (PFS) at 3 years was 70% and 58% in entire cohort, 78% and 62% in HL and 51% and 46% in NHL subgroup, respectively. International Prognostic Score (IPS) >2 at relapse prognosticated for poor OS (P = 0.002) and PFS (P < 0.001) in HL subgroup. Positron emission tomography positivity pretransplant (HL subgroup) and at day + 100 (NHL subgroup) predicted for poor survival. Conclusion: We conclude that LACE is effective and well-tolerated conditioning regimen. IPS at relapse is the most important prognostic factor in HL transplant.

Killer Immunoglobulin like Receptor-Human Leukocyte Antigen Ligand Match/Mismatch in Graft Loss Post Transplant Cyclophosphamide Based Hap loidentical Transplant

Background: Killer Immunoglobulin like receptor (KIR) genes that modulate Natural Killer cell alloreactivity have been linked with predicting haploidentical hematopoietic stem cell transplant outcomes. Study design and methods: We present two haploidentical hematopoietic stem cell transplant (HHSCT) scenarios, wherein after engraftment there was graft loss. We hypothesized that this phenomenon was due to KIR ligand matches/mismatches. The KIR ligand matches/mismatches were examined in both patient donor pairs. Results: Patient 1 and 2 were 11/12 and 12/12 match for HLA A, B, C, DRB1, DQB1 and DPB1 in GvH respectively, and their donors were 6/12 and 7/12 HLA match in HvG directions. It was observed that there was KIR activating receptor (aKIR) match and stronger KIR inhibitory receptor (iKIR) mismatch in GvH direction which resulted in removal of leukemic cells. Moreover, in the HvG direction, the stronger aKIR match led to graft rejection. Conclusion: This study highlights the implication of KIR-HLA interaction in predicting graft survival. Citation: D’Silva SZ, Diwedi P, Punatar S, Gokarn A, Bonda A, et al. (2018) Killer Immunoglobulin like Receptor-Human Leukocyte Antigen Ligand Match/Mismatch in Graft Loss Post Transplant Cyclophosphamide Based Hap loidentical Transplant. J Blood Lymph 8: 225. doi: 10.4172/2165-7831.1000225

Leflunomide: Is It the Game Changer in Musculoskeletal Chronic Graft Versus Host Disease?

Musculoskeletal involvement in chronic graft versus host disease (cGVHD) can be extremely crippling. Manifestations of musculoskeletal cGVHD are varied and can include fasciitis, myositis, weakness, cramping, joint stiffness and contractures. Pathogenetically, in musculoskeletal GVHD there is accumulation of alloimmune donor T-cells in the muscles, joints, and soft tissues. Release of cytokines by these activated T-cells results in fibroblast proliferation and activation. Cross talk between these alloimmune T-cells with macrophage will further augment the fibrosis. Alloimmune donor T cells also activate B-cells resulting in the production of auto antibodies directed against joints and muscular tissues [1]. Thus, pathophysiology of musculoskeletal GVHD closely mimics many autoimmune disorders. Though systemic steroids may improve clinical manifestations of musculoskeletal GVHD, prolonged usage of steroids is associated with several long term complications and predisposition to infections. Steroid sparing agents like Cyclosporine, Tacrolimus, Sirolimus, Mycophenolate mofetil, Etanercept, Low dose Methotrexate have been used with variable success. Olivieri et al. [2] described the role of Imatinib in chronic GVHD associated with fibrotic changes. Many of these drugs are associated with adverse effects like reactivation of infections, organ toxicities and some of them are costly. Leflunomide with its anti-T cell proliferative action has shown to be useful in rheumatoid arthritis [3]. Leflunomide has been shown to be effective in prevention and treatment of GVHD in various animal models [4, 5]. We describe our patient with Musculoskeletal GVHD who responded to single agent Leflunomide. A 46 year old female with Myelodysplastic syndrome (RAEB2) with progression to acute myeloid leukemia underwent haploidentical stem cell transplant with her 8/10 HLA matched son. Her baseline comorbidities included remote hepatits B infection for which she was on prophylaxis with lamivudine. Her conditioning regimen was reduced intensity with fludarabine, and treosulfan. GVHD prophylaxis consisted of cyclosporine (CsA), mycofenolate mofetil (MMF) and post-transplant cyclophosphamide. Her immediate post-transplant period was complicated by febrile neutropenia, voriconazole induced visual hallucinations and CsA related headache. She engrafted on day ? 11 and developed engraftment related fever needing low dose steroids for few days. MMF was stopped on day ? 36 and CsA tapering was started from day ? 91. On Day ? 125 her liver enzymes were found to be mildly elevated on routine blood workup. Virology testing did not show any seroconversion. HBV DNA and HCV RNA PCR were negative. She was continued on lamivudine. Suspecting liver GVHD, cyclosporine tapering was withheld temporarily. Her liver enzymes showed a declining trend by day ? 130. On day ? 133 she started having bilateral shoulder pain with some restriction of movements. This worsened gradually and 2 weeks later (day ? 144), she had severe restriction of movements, increased pain, joint stiffness in small joints of hand and difficulty in getting up from sitting position. MRI of shoulder joints ruled out avascular necrosis. A clinical diagnosis of musculoskeletal GVHD was made. Her baseline PROM score was 21 and NIH joint score was 2. Since her manifestations resembled rheumatoid arthritis, she was started on oral leflunomide (100 mg once a day for first 3 days followed by 20 mg & Navin Khattry nkhattry@gmail.com

Outcomes of Patients with Splenic Marginal Zone Lymphoma Treated with Rituximab or Splenectomy: Report from Tertiary Cancer Center in India

S282 Context: Castleman ’s Disease (CD) is the rare lymphoproliferative disease masking a number of hematologic, oncological and autoimmune diseases. Objective: To determine the frequency of occurrence of the diseases which are followed by Castleman-like similar changes in lymph nodes. Materials and methods: Medical records of the 48 patients with preliminary diagnosis CD directed in outpatient department from 2016 to 2017. All patients were examined according to the recommendations of the international working group on the study of CD. Morphological study of lymph node tissue biopsies included the assessment of regressed or hyperplastic germinal centers, follicular dendritic cell prominence, vascularization and polytypic plasmacytosis in the interfollicular spaces by the point system from 0 to 3 grades. Results: Morphological picture in 24 lymph node tissue biopsies, from 24 of 48 patients corresponded to the first large criterion of diagnosis of CD. In these cases, comparison of clinical and laboratory data allowed to confirm the diagnosis of C D. The greatest divergence was observed in cases with a generalized lymphadenopathy. From 15 patients with the preliminary diagnosis multicentric CD the diagnosis has been confirmed in 20%. Diagnosis CD was changed to the Hodgkin’s lymphoma (HL) in three cases, to NHL in three cases, to the connective tissue disease and solid tumors in two cases respectively, to primary amyloidosis in one patient, and to multiple myeloma in one patient. In cases with local specific involvement the diagnosis of CD has been confirmed in 63.6%. The range of the revealed diseases included: a reactive lymphadenopathy in 6 cases, a tumor not of the lymphoid nature in two cases, HL at the one patient and NHL at the three patients. Conclusion: Inspection of patients with suspected diagnosis of CD according to the recommendations of the international working group has shown that the frequency of occurrence of the diseases which are followed by Castleman-like similar changes in lymph nodes varies from 36,4 to 80% and depends on prevalence of process. The range of the diseases demanding an exception includes HL and NHL, connective tissue disease, other neoplastic processes and reactive conditions.