Improved Outcome of Refractory/Relapsed Acute Myeloid Leukemia after Post-Transplantation Cyclophosphamide-Based Haploidentical Transplantation with Myeloablative Conditioning and Early Prophylactic Granulocyte Colony-Stimulating Factor-Mobilized Donor Lymphocyte Infusions.

We carried out post-transplantation cyclophosphamide (PTCy)-based haploidentical peripheral blood stem cell transplantation in 51 patients with refractory/relapsed acute myeloid leukemia not in remission. The first 10 patients received nonmyeloablative conditioning followed by planned granulocyte colony-stimulating factor (G-CSF)-mobilized donor lymphocyte infusions (DLIs) on days 35, 60, and 90. No patient developed graft-versus-host disease (GVHD), but 90% had disease progression between 3 and 6 months. A subsequent 41 patients received myeloablative conditioning (MAC); the first 20 patients did not receive DLIs (MAC group) and the next 21 patients received G-CSF-mobilized DLIs (G-DLI) on days 21, 35, and 60 (MAC-DLI group). The incidence of disease progression and progression-free survival at 18 months were 66% and 25% in the MAC group compared with 21.4% and 61.9% in the MAC-DLI group (P = .01). Chronic GVHD but not acute GVHD was increased in the MAC-DLI group (41.2% versus 11%, P = .05). Natural killer cell alloreactive donor was associated with lower incidence of disease progression in the MAC but not in MAC-DLI group. The only factor favorably influencing disease progression and progression-free survival was administration of G-DLI after myeloablative conditioning. Our study shows that early administration of G-DLI is feasible after PTCy-based haploidentical hematopoietic stem cell transplantation for refractory/relapsed acute myeloid leukemia and might be associated with improved survival after MAC.

Retrospective Review of Platelet Transfusion Practices during 2013 Dengue Epidemic of Delhi, India.

BACKGROUND: Dengue infection is a major public health problem. During explosive outbreaks, there is sudden surge in demands of platelet products. The present study was carried out in order to review platelet transfusion practices during the epidemic of dengue. METHODS: We retrospectively reviewed the clinical details including the platelet counts and haemorrhagic tendencies of dengue patients as well as the transfusion requirements of diagnosed dengue cases admitted at our centre. RESULTS: A total of 1,750 random donor platelet and 114 single donor platelet units were transfused to 531 patients. 23.2% platelet transfusions were found to be inappropriate Mean dosage of platelets transfused was 2 × 10(11) platelets per patient. A total of 347 (65.3%) patients had bleeding diathesis at the time of presentation. Skin and the oropharynx were the most common bleeding sites. Major bleeding was seen in 119 (34.3%) patients, whereas 228 (65.7%) patients had minor bleeding episodes. CONCLUSION: The study emphasises the need for minimising unnecessary transfusions and for using this scarce resource judiciously, which can be achieved by strict adherence to evidence-based transfusion guidelines and regular review of the on-going transfusion practices.

Measuring the effectiveness of an integrated intervention package to improve the level of infection prevention and control: a multi-centre study in Bangladesh.

BACKGROUND: Infection prevention and control (IPC) is a critical component of delivering safe, effective and high-quality healthcare services, and eliminating avoidable healthcare-associated infections (HAIs) in health facilities, predominantly in population-dense settings such as Bangladesh. AIM: Our study aimed to assess the effect of an integrated intervention package in improving the IPC level of the health facilities in Bangladesh. METHODS: We conducted a pre-post intervention study in six district hospitals (DHs) and 13 Upazila Health Complexes (UHCs) in the six districts of Bangladesh. Baseline and endline assessments were conducted between March and December 2021 using the adapted World Health Organization Infection Prevention and Control Assessment Framework (WHO-IPCAF) tool. The IPCAF score, ranging from 0-800, was calculated by adding the scores of eight components, and the IPC promotion and practice level was categorized as Inadequate (0-200), Basic (201-400), Intermediate (401-600) and Advanced (601-800). The integrated intervention package including IPC committee formation, healthcare provider training, logistics provision, necessary guidelines distribution, triage/flu corners establishment, and infrastructure development was implemented in all facilities. RESULTS: The average IPCAF score across all the facilities showed a significant increase from 16% (95% CI: 11.5-20.65%) to 54% (95% CI: 51.4-57.1%). Overall, the IPCAF score increased by 34 percentage points (P<0.001) in DHs and 40 percentage points (P<0.001) in UHCs. Following the intervention, 12 (three DHs, nine UHCs) of 19 facilities progressed from inadequate to intermediate, and another three DHs upgraded from basic to intermediate in terms of IPC level. CONCLUSION: The integrated intervention package improved IPCAF score in all facilities.

Crystallizing galactocele of the breast masquerading as a malignancy: Report of a rare case with cytological diagnosis.

Galactoceles are the common benign cystic breast lesions during pregnancy and lactation. This report describes the cytological findings of a case of long standing galactocele which underwent crystallization and mimicked carcinoma clinically as well as on sonography. A young woman presented with a hard painless lump in the right breast. She noticed the lump during her pregnancy 2.5 years back. Clinically the lesion was hard and sonography was equivocal in categorizing the lesion. An FNAC was performed which showed granular amorphous material along with crystals of various shapes and sizes. A diagnosis of crystallizing galactocele was made and woman was assured about the benign nature of the lesion. The cytological findings of crystallizing galactocele have been reported in very few cases. In the present case, a detailed history and clinical examination followed by fine needle aspiration established the diagnosis of crystallizing galactocele.

T cell costimulation blockade promotes transplantation tolerance in combination with sirolimus and post-transplantation cyclophosphamide for haploidentical transplantation in children with severe aplastic anemia.

We conducted a pilot study employing extended T cell costimulation blockade (COSBL) with Abatacept along with sirolimus and post-transplantation cyclophosphamide (PTCy) in 10 patients (median age 12) with severe aplastic anemia (SAA). Nine patients engrafted in the COSBL group, compared to all 10 patients (median 14 vs 13days) treated on PTCy protocols without abatacept (CONTROL group). The incidence of acute graft-versus-host disease (GVHD) was 10.5% in the COSBL group compared to 50% in the CONTROL group (p=0.04). Chronic GVHD (12.5% vs 56%, p=0.02) and CMV reactivation (30% vs 80%, p=0.03) were also reduced in the COSBL group. T and NK cell subset analysis revealed higher CD56brightCD16- NK cells in the CONTROL group (p=0.004), but similar CD56dimCD16+ NK cells in both groups at day+30. Tregs (CD4+CD25+CD127dim/- FoxP3+) were markedly higher in the COSBL group at day+30 (8.4% vs 1.1%) and the trend was maintained through day+90 (p<0.01). The GVHD and Disease-free survival at one year in the COSBL group was 80% vs. 30% in the CONTROL group (p=0.05). Our preliminary findings suggest that COSBL in combination with PTCy and sirolimus might augment transplantation tolerance in children with SAA, probably due to synergistic effect on early recovery of Tregs.

Comparison of Procleix Ultrio Elite and Procleix Ultrio NAT Assays for Screening of Transfusion Transmitted Infections among Blood Donors in India.

Background. Introduction of nucleic acid testing (NAT) has helped in decreasing window period donations, resulting in increased safety of blood supplies. NAT combines the advantages of direct and highly sequence-specific detection of viral genomes. We analysed the performance of newer Procleix Ultrio Elite (PUE) and Procleix Ultrio assay (PUA) for the screening of the viral markers in our donor population. Material and Methods. 10,015 donor samples were screened by routine immunoassays and both versions of NAT. NAT yields detected were subjected to viral load estimation and to other serological markers. Results. A total of 21 NAT yields were detected; three were positive by both NAT systems, whereas 18 samples were reactive by PUE only. NAT yields include 18 HBV and 3 HCV yields, of which 17 HBV yields were occult infections and 1 was window period (WP) infection. All 3 HCV yields were WP infections. No HIV-1/HIV-2 yield was found. Conclusion. Efficient target capture chemistry in the new TMA assay version significantly improved sensitivity. NAT is superior to serological immunoassays for screening of the viral markers; and the efficient target capture system in the newer TMA assay, namely, the PUE system, has significantly improved sensitivity over the earlier versions.

T cell costimulation blockade for hyperacute steroid refractory graft versus-host disease in children undergoing haploidentical transplantation.

The outcome of hyperacute grade 3-4 steroid-refractory graft-versus-host-disease (SR-GVHD) remains dismal despite a plethora of agents being tried alone or in combination. Following T replete haploidentical transplantation with post-transplantation cyclophosphamide on 75 patients, 10 patients (13%) aged 2-20years, developed hyperacute SR-GVHD. We report on the outcome of two different regimens for treatment of SR-GVHD on the outcome of these patients. Five patients were treated in Regimen A consisting of anti-thymocyte globulin, Etanercept and Basiliximab. The next 5 patients were treated combining T cell costimulation blockade with Abatacept along with Etanercept and Basiliximab. The overall response at days 29 and 56 were 40% and 0% with Regimen A and100% and 40% with Regimen B. The major cause of treatment failure was progression of GVHD and opportunistic infections. Two of the patients achieving a complete remission on Regimen B are long term disease free survivors off immunosuppression. Our study demonstrates the dismal outcome of early onset SR-GVHD in children following T replete haploidentical transplantation. However, the combination of Abatacept with anticytokine agents seems to produce encouraging early response and might warrant further investigation.

Evaluation of Mirasol pathogen reduction system by artificially contaminating platelet concentrates with Staphylococcus epidermidis: A pilot study from India.

BACKGROUND AND OBJECTIVES: This study was conducted to assess the efficacy of Mirasol pathogen reduction system for platelets aimed at preventing bacterial regrowth by spiking buffy coat pooled platelets (BCPP) with clinically relevant load of Staphylococous epidermidis. MATERIALS AND METHODS: BCPP units were prepared using Teruflex BP-kit with Imugard III-S-PL (Terumo BCT, Tokyo, Japan). Two BCPP units were pooled, of which 40 ml of negative control (NC) was removed. The remaining volume of the platelet unit was inoculated with clinically relevant load of bacteria (total of 30 CFU of S. epidermidis in 1 ml); following this the platelet unit was split into two parts. One part served as positive control (PC) and the other part was subjected to pathogen reduction technique (Mirasol PRT, CaridianBCT Biotechnologies, Lakewood, CO, USA). Bacterial detection was performed using BacT/ALERT system, controls after day 1 and day 7 following inoculation of bacteria and on day 7 for Mirasol-treated unit. RESULTS: Of the 32 treatment cycles, 28 were valid and 4 were invalid. No regrowth was observed in 96.4% (27 of 28) after treatment with Mirasol pathogen reduction system. Of four invalid tests, on two instances the NC showed growth, whereas in other 2 no regrowth was detected in 7(th) day PC. Bacterial screening of PCs by BacT/ALERT after 24 h of incubation was 28.6%, whereas the effectiveness increased to 100% when incubated for 7 days. CONCLUSIONS: Mirasol system was effective in inactivating S. epidermidis when it was deliberately inoculated into BCPP at clinically relevant concentrations. Such systems may significantly improve blood safety by inactivating traditional and emerging transfusion-transmitted pathogens.

Screening Donated Blood for Transfusion Transmitted Infections by Serology along with NAT and Response Rate to Notification of Reactive Results: An Indian Experience.

Background. Transfusion safety begins with healthy donors. A fundamental part of preventing transfusion transmitted infections (TTIs) is to notify and counsel reactive donors. Donor notification and counselling protect the health of the donor and prevent secondary transmission of infectious diseases. Methods. 113,014 donations were screened for TTIs, namely, HIV, HBV, HCV, and syphilis, by serology and nucleic acid testing. All reactive donors were retested (wherever possible) and notified of their status by telephone or letter. All initial reactive screens were followed over six months. Results. We evaluated 2,838 (2.51%) cases with reactive screening test results (1.38% HBV, 0.54% HCV, 0.27% HIV, and 0.32% syphilis). Only 23.3% of donors (662) responded to notification. The response among voluntary donors was better as compared to the replacement donors (43.6% versus 21.2%). Only 373 (56.3%) responsive donors followed their first attendance at referral specialties. Over six months, only 176 of 662 (26.6%) reactive donors received treatment. Conclusion. Our study shed light on the importance of proper donor counselling and notification of TTI status to all reactive donors who opt to receive this information. There is also an urgent need to formulate the nationally acceptable guidelines for notification and follow-up of reactive donors.

Prevalence and Specificity of RBC Alloantibodies in Indian Patients Attending a Tertiary Care Hospital.

Background. Red blood cell (RBC) alloimmunization results from genetic disparity of RBC antigens between donor and recipients. Data about alloimmunization rate in general patient population is scarce especially from resource limited countries. We undertook this study to determine prevalence and specificity of RBC alloantibodies in patients admitted in various clinical specialties at a tertiary care hospital in North India. Methods. Antibody screening was carried out in 11,235 patients on automated QWALYS 3 platform (Diagast, Loos, France). Antibody identification was carried out with an 11-cell identification panel (ID-Diapanel, Diamed GmbH, Switzerland). Results. The overall incidence of RBC alloimmunization in transfused patients was 1.4% (157/11235), with anti-E being the most common specificity (36.3%), followed by anti-D (16%), anti-c (6.4%), anti-c + E (6.4%), anti-C + D (5.1%), and anti-K (4.5%). The highest incidence of alloimmunization was observed in hematology/oncology patients (1.9%), whereas in other specialties the range was 0.7-1%. Conclusion. As alloimmunization complicates the transfusion outcomes, authors recommend pretransfusion antibody screening and issue of Rh and Kell matched blood to patients who warrant high transfusion requirements in future.

Complications associated with Plasmodium vivax malaria: a retrospective study from a tertiary care hospital based in Western Uttar Pradesh, India.

BACKGROUND: Plasmodium vivax (p. vivax) malaria was traditionally considered as benign tertian malaria, however, recent studies have pointed out that p. vivax have potential to cause all severe complications previously attributed to p. falciparum infection only. The aim of this report is to study the incidence of various clinical and biochemical complications associated with severe p. vivax malaria. METHODS: A retrospective analysis was performed on all patients with p. vivax malaria admitted to our center between January 2009 and December 2011. Severe malaria was defined as per World Health Organization (WHO) criteria. Clinical and laboratory parameters were recorded. Patients with evidence of p. falciparum, mixed malarial infection and chronic systemic diseases were excluded from the study. RESULTS: Sixty-two patients met the criteria for severe malaria during the study period. The complications observed were Hepatic dysfunction in 18 (29%), renal dysfunction in 13 (21%), cerebral malaria in 10 (16.1%), acute respiratory distress syndrome (ARDS) in 6 (9.7%), shock in 10 (16.1%), severe anemia in 16 (25.8%), thrombocytopenia in 35 (56.5%), and hypoglycemia in 3 (4.8%) patients. Three mortalities were observed. CONCLUSIONS: P. vivax has immense potential to cause life threatening complications and even death, more research is required to understand the exact pathogenesis of various complications encountered in vivax malaria.

Life-threatening calcium channel blocker overdose and its management.

A young woman presented to the emergency department with complaints of nausea, vomiting, pain in the abdomen and difficulty in breathing after ingestion of 56 tablets of amlodipine 5 mg each (total 280 mg of amlodipine). She was managed using hyperinsulinaemia/euglycaemia therapy and other measures like calcium gluconate, glucagon and vasopressors. She was discharged from hospital in a stable condition after 5 days.

Acute life-threatening methaemoglobinaemia following ingestion of chloroquine.

A 25 year old man was rushed to the emergency department when he was found unconscious in his room after taking two chloroquine tablets (600 mg base) for fever prescribed by local practitioner. On examination, the patient was unconscious and deep cyanosis was present on lips, tongue, oral cavity, nail beds and finger tips. Subsequent laboratory investigation revealed methaemoglobin level of 54%. Diagnosis of chloroquine-induced methaemoglobinaemia was made and methylene blue (1 mg/kg) was administered. The patient improved dramatically and was discharged following day.

Superior vena cava syndrome caused by Hodgkin's lymphoma in an adolescent girl.

A 14-year-old female patient presented to us with complaints of shortness of breath, swelling over upper body and dysphagia, prominent veins were visible on upper body. CT scan of chest revealed a large mediastinal mass compressing surrounding structures. Histopathology and immunohistochemistry confirmed it to be Hodgkin's lymphoma. The patient was given a course of chemotherapy (doxorubicin, bleomycin, vinblastine and dacarabazine) and local radiotherapy. Presently she is doing well.