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An outbreak of type C botulism in four week - old broilers in an open farm house is described. Botulism is an intoxication caused by exotoxins of Clostridium botulinum. At 4 weeks of age, an increase in mortality was observed in the broilers. Clinically, the birds presented with paralysis of the legs, wings, and neck. Affe cted birds were sitting and reluctant to move. Necropsy failed tofind any specific lesions. Except water, investigations of environmental samples to detect the source of the toxin were not successful despite repeated testing. DNA of C. botulinum type C wa s detected by PCR in liver, heart, muscles and crop. The result was confirmed by a mouse lethality neutralization test. During the 2 weeks after the onset of the clinical signs the mortality was about 47.8%. After 2 weeks, clinical signs and mortality abated. [ABSTRACT FROM AUTHOR]

Treatment options for newly diagnosed aplastic anemia (AA) patient includes upfront allogeneic hematopoietic stem cell transplant (HSCT) or immunosuppressive therapy (IST). With recent advances in supportive care, conditioning regimens and post-transplant immunosuppression the overall survival for HSCT approaches 70–90%. Transplant eligibility needs to be assessed considering age, comorbidities, donor availability and probability of response to immunosuppressive therapy (IST). Upfront HSCT should be offered to children and young adults with matched related donor (MRD). Upfront HSCT may also be offered to children and young adults with rapidly available matched unrelated donor (MUD) who require urgent HSCT. Bone marrow (BM) graft source and cyclosporine (CsA) plus methotrexate (MTX) as graft versus host disease (GVHD) prophylaxis are preferable when using anti-thymocyte globulin (ATG) based conditioning regimens. Alemtuzumab is an acceptable alternative to ATG and is used with CsA alone and with either BM or peripheral blood stem cells (PBSC). Cyclophosphamide (CY) plus ATG conditioning is preferable for patients receiving MRD transplant, while Fludarabine (Flu) based conditioning is reserved for older adults, those with risk factors of graft failure and those receiving MUD HSCT. For haploidentical transplant, use of low dose radiotherapy and post-transplant cyclophosphamide has resulted in a marked reduction in graft failure and GVHD. • Transplant outcomes for aplastic anemia continues to improve with time, overall survival after MUD and Haploidentical transplant is now approaching MRD HSCT. • Bone marrow graft source and cyclosporine plus methotrexate GVHD prophylaxis are preferable. • Cyclophosphamide plus ATG conditioning is preferable for younger patients receiving MRD transplant, while Fludarabine based conditioning is reserved for older adults, with risk factors for graft failure and those receiving MUD HSCT. [ABSTRACT FROM AUTHOR]

Hemophagocytic Lymphohistiocytosis (HLH) is a rare disorder of immune dysregulation characterized by fever, cytopenias, and splenomegaly. Its primary form poses a therapeutic challenge due to its high fatality when left untreated. We retrospectively analyzed 28 patients who underwent related-donor allogeneic stem cell transplant for primary HLH from 2010 to 2021. Among them were 10 cases of familial HLH, 8 cases of Griscelli syndrome type 2, and 1 case each with PRF1 and STX11 mutations. All the patients underwent transplants with reduced-intensity or myeloablative conditioning and 26 of them achieved neutrophil engraftment at a median of day + 14. The donors were either fully matched (68%) or haploidentical (32%). With a median follow-up of 1 year, overall survival was 68% (n = 19) and disease-free survival was 64.4% (n = 18). OS was better in patients transplanted with a sibling donor (compared to parent donor), who achieved complete donor chimerism, and those transplanted early in the course of the disease (diagnosis to transplant duration less than 6 months). [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding a study on the quality of life among stroke survivors and primary caregivers in Pakistan.

Objectives: Hepatic Veno occlusive disease (VOD), also known as sinusoidal obstruction syndrome (VOD/SOS), is a post-transplant life threatening complication. In this study, we aimed to discuss the incidence, management and outcome of VOD in post allogenic transplant patients of beta thalassemia major (BTM). Methods: A prospective study was conducted in Armed Forces Bone Marrow Transplant Center, between 2001-2022. A total of 385 fully Human Leucocyte Antigen (HLA) matched BTM patients, with Ursodeoxycholic acid for prophylaxis, were included in the study. Incidence of VOD was calculated through cumulative incidence estimates. Chi square test and Mann Whitney test were used to compare discrete and continuous variables respectively. VOD was diagnosed and graded according to European Society for Blood and Marrow Transplantation EBMT Pediatric diagnostic criteria. Risk factors for VOD were grouped as recipient, transplant and donor related. Univariate analysis was performed by log-rank test. All patients who developed VOD were managed primarily with fluid restriction and strict input output monitoring. Statistical analyses were performed using SPSS v 25.0. Results: Out of 385 transplant patients, forty developed VOD. Median time from date of transplant till onset of VOD was 14 days (range 6-30). Cumulative incidence of all grade VOD was 10.39% (95% CI, 7-14). Eleven out of 40 patients who developed VOD died. Cumulative incidence of Transplant related mortality (TRM) for patients with and VOD was 20.5% (95% CI, 16.6-25.1) vs 27.5% (95% CI, 16.1-42) (p value 0.318) respectively. Among risk factors, age of recipient and fibrosis (p value of 0.04 and 0.000 respectively) were found to be significantly associated with VOD. Conclusions: Careful selection of transplant candidates before transplant can help reduce the incidence of VOD. [ABSTRACT FROM AUTHOR]

A series of four energetic transition metal coordination compounds (cobalt, zinc, copper, and cadmium) were synthesized using a 1-amino-tetrazol-5-one (ATO) ligand. The mechanical sensitivities (impact and friction) and flame tests classified them as potential insensitive energetic materials and pyrotechnics. [Display omitted] • New energetic transition metal coordination compounds (CCs) based on versatile and multifunctional 1-amino-tetrazol-5-one ligand were synthesized. • The prepared CCs were characterized by the single-crystal X-ray diffraction technique. • Good mechanical sensitivities towards impact and friction were observed. • The CCs presented a range of distinguishing flame colors. • These compounds have potential to be use as insensitive energetic materials. New energetic transition metal (Co, Cu, Zn, and Cd) coordination compounds (CCs) based on versatile and multifunctional 1-amino-tetrazol-5-one ligand were prepared by using a facile strategy. All the synthesized CCs were characterized by single-crystal X-ray diffraction. They crystallize in common space groups with high densities in the range of 2.246 to 2.598 g·cm−3 and their onset decomposition temperatures were found in the range of 292 °C (CC1) to 327 °C (CC3). Further investigations revealed that in addition to the coordination bonds the strong hydrogen bond interactions also exist, which ultimately decided the crystal structure engineering and physical properties of the resultant CCs. The mechanical sensitivities towards impact and friction were evaluated using standard methods and as a result, the energetic metal CCs are were classified as insensitive. The flame test of these energetic metal CCs showed a range of characteristic flame colors from light blue to blue-green except for the cadmium coordination compound, which indicates colorless flame. Hence, the insensitivities of these CCs towards impact and friction as well as characteristic flame colors support their potential use as insensitive energetic materials or pyrotechnics. [ABSTRACT FROM AUTHOR]

A series of pyrimidine-derived Schiff bases (1 – 6) of hydroxy-1-naphthaldehyde were synthesized and completely characterized. The molecular docking studies of these synthesized compounds reveals that all the compounds are bioactive, however compound 5 shows significant antibacterial, antioxidant, antifungal, and anticancer properties over standard drugs. [Display omitted] • Pyrimidine-derived Schiff bases (1 – 6) of hydroxy-1-naphthaldehyde were synthesized by using the condensation method. • The molecular docking studies were carried out to explore the antibacterial, antioxidant, antifungal and anticancer properties respectively. • Identify the binding interactions of synthesized compounds against receptors. • The synthesized pyrimidine Schiff bases (1 – 6) are bio-active and exhibited better binding affinities as compared to the standard drugs. Pyrimidine which is an important constituent of the genetic material of deoxyribonucleic acid, is identified with a large number of biological activities. Based on this, pyrimidine-derived Schiff bases (1 – 6) of hydroxy-1-naphthaldehyde were synthesized by using the condensation method. In addition, the molecular docking studies against topoisomerase II DNA gyrase, human hematopoietic cell kinase, urate oxidase from Aspergillus flavus, and cyclin-dependent kinase 8 to explore the antibacterial, antioxidant, antifungal, and anticancer properties respectively and binding affinities through bioinformatics approaches to determine the interaction among active molecules with the receptor. Hence, the computational docking analyses identified that all synthesized pyrimidine Schiff bases (1 – 6) are active and exhibited better binding affinities as compared to the standard drugs. Furthermore, all the prepared materials were characterized by using nuclear magnetic resonance, infrared, and elemental analysis. Additionally, the phase-transition and thermal decomposition temperatures were determined by differential scanning calorimetry and thermo-gravimetric analysis measurements. Moreover, the structures of pyrimidine-derived Schiff bases 1, 2, 3, 4, and 5 were also confirmed by the X-ray single-crystal diffraction technique. The pyrimidine-derived Schiff bases 5 possess significant antibacterial, antioxidant, antifungal, and anticancer agent properties which confirms its promising biological activities over standard drugs. [ABSTRACT FROM AUTHOR]

Interaction of environmental and genetic elements plays a vital role in the pathogenesis of aplastic anemia (AA). Glutathione S-transferase (GST) is a key detoxifying enzyme. Absence or low levels of this enzyme may genetically predispose individuals to AA. GST genes GSTM1 and GSTT1 are polymorphic. The aim of this study was to screen Pakistani AA patients and controls for GSTM1 deletion GSTM0 and GSTT1 deletion GSTT0 and perform meta-analysis using our data and other published data regarding these polymorphisms. DNA samples from 137 patients and 220 controls were screened using multiplex polymerase chain reaction. GSTM0 emerged as susceptible genotype for AA in Pakistan with a percentage frequency of 49.6 % as compared to 30 % in controls with odds ratio (OR) of 2.25, 95 % confidence interval (CI) of 1.4-3.5 and corrected p = 0.006. The meta-analysis showed a significant association between the null genotype GSTT0 and AA in overall analysis with OR of 1.47, 95 % CI of 1.01-2.13 and p value of 0.04 in random effects model. Studies like these could play a role in understanding the underlying path in AA pathogenesis and therefore can help in designing means for prevention, diagnose and treatment. [ABSTRACT FROM AUTHOR]

• A cation 3-(5-amino-1H-1,2,4-triazol-3-yl)−1,2,4-oxadiazol-5-amine was obtained. • Four salts were synthesized and characterize using X-ray diffraction technique. • The visual analysis of the intermolecular interactions was achieved. • Extensive hydrogen bonding and π-π interactions promote their good stability. • Energetic salts AOATP and AOATN exhibited acceptable comprehensive performances. A novel coplanar bicyclic cation 3-(5-amino-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazol-5-amine (AOAT) was proposed to widen the research of energetic cations, and four salts were synthesized via neutralization reaction in high yield. The single-crystal X-ray diffraction, multinuclear NMR (1H and 13C), IR, MS spectra, elemental analysis, differential scanning calorimetry (DSC), and thermos-gravimetric (TG) analysis techniques were employed to verify and characterize the structures and thermal stability of the four salts respectively. Based on the combination of experimentally determined densities and enthalpies of formation, the energetic properties of the two energetic salts AOATP and AOATN were determined using EXPLO5 program. Compared with those known energetic salts, AOATP and AOATN exhibited high densities (1.829–1.871 g·cm−3), acceptable detonation performance (D: 8359–8465 m·s−1; P: 28.4–30.3 GPa), good thermal stability (T d : 177–238 °C), as well as satisfied mechanical sensitivities (IS: 16–22 J; FS: 188–216 N). Hirshfeld surfaces and assiciated 2D fingerprint plots as well as non-covalent interactions were adopted to examine the intermolecular interactions of the four salts. The results indicate that ionic bonds, hydrogen bonds, and π-π stacking interactions are responsible for the high densities and excellent properties of 5-amino-3-(5-amino-1,2,4-oxadiazol-3-yl)-1H-1,2,4-triazolium perchlorate and nitrate salts, suggesting that the AOAT is a potential cation in the construction of high-performance energetic materials and that cations with coplanar conjugated structures could effectively improve the detonation properties and stability. A nitrogen-rich cation 3-(5-amino-1H-1,2,4-triazol-3-yl)-1,2,4-oxadiazol-5-amine (AOAT) with coplanar and conjugated features was proposed and four salts of AOAT were synthesized. Two energetic salts had good detonation performance and safety compared with other known corresponding energetic salts, which is significant and instructive for further study in energetic cation salts. [Display omitted] [ABSTRACT FROM AUTHOR]

• The NTAPDO 1 and NTAPMO 2 were synthesized by mild oxidation reactions and energetic salts (3–5) by neutralization reaction. • The structures of all the prepared compounds (1–5) were investigated using the single-crystal X-ray diffraction technique. • Thermal behaviors of title compounds were studied by DSC and TG methods. • All compounds possessed high positive HOFs and good sensitivities (impact and friction). The N-oxidation of 5-Nitroso-2,4,6-triaminopyrimidine leads to the successful synthesis of 5-Nitro-2,4,6 triaminopyrimidine-1,3-Dioxide (NTAPDO) 1 and 5-Nitro-2,4,6-triaminopyrimidine-1-oxide (NTAPMO) 2 by using mild oxidation reactions and the NTAPMO (2) based energetic salts (3–5) were prepared effectively by reacting 2 with the related acids following neutralization reaction. The single-crystal X-ray diffraction, differential scanning calorimetry (DSC), and thermal gravimetric analysis (TGA) techniques were applied to manifest the structures and thermal stability of compounds respectively. The compounds 1–5 exhibited high densities in the range of 1.76 -1.87 g.cm−3 and mechanically insensitive towards impact and friction. The heat of formation (HOF) of these compounds was found high positive between the ranges of 207.7 to 768.4 kJ.mol−1. The energetic salts 3, 4, and 5 demonstrated high detonation performance (velocity and pressure) and high volumes of explosion gasses (789.77, 733.85, and 730.61 L•kg−1, respectively). Hence, compounds 1–5 displayed good thermal stability, high positive HOFs, and good detonation performance as well as low sensitivity suggesting their potential to be used as energetic materials in the field of high-performance explosives. [ABSTRACT FROM AUTHOR]

Background: Oxidative damage has been implicated in multiple neurodegenerative diseases, including epilepsy. Selenium, in the form of selenoproteins is an integral part of the human antioxidant defense system. Though a relationship between the altered selenium levels and epilepsy has been reported, limited evidence is available about the expression pattern of selenoproteins in epileptic patients., Objective: This study aimed to determine the serum selenium levels in idiopathic epileptic and healthy individuals. Expression profiling of selenoproteins (GPx1, TRxR1 and SEPW1) both at mRNA and protein levels was also evaluated., Methods: Serum selenium levels of 30 patients with idiopathic generalized epilepsy and their age and gender matched 30 healthy controls were measured. Protein levels of Serum Glutathione Peroxidase 1 (GPx1), Thioredoxin Reductase 1 (TRxR1) and Selenoprotein W (SEPW1) were estimated using ELISA. mRNA expression of GPx1, TRxR1 and SEPW1 were determined using qRT-PCR., Results: The mean values for serum selenium levels in cases and controls were 37.6 ± 2.0 µmol/ml and 38.9 ± 2.7 µmol/ml, respectively. Selenium levels in cases were significantly lower as compared to controls (p = 0.031). No statistically significant differences were observed between the serum levels of selenoproteins GPx1, TRxR1 and SEPW1 in epileptic patients and the healthy group. GPx1 and TRxR1 expression was found to be down regulated (0.34 and 0.13 folds respectively) whereas SEPW 1 was found to be 0.04 folds up regulated in epileptic patients compared to the healthy subjects., Conclusion: Selenium deficiency observed in epileptic patients suggests the association between serum selenium levels and epilepsy. This study provides the information about the selenium status in Pakistani population and helps in understanding the role of selenium in the prevention of epilepsy., Competing Interests: Declarations. Ethics approval and consent to participate: “This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Institutional review board, Dow University of Health Sciences, Karachi (IRB-1438/duhs/Approval/2020 dated 30th January-2020).” Written informed consent was obtained from all individual participants included in the study.” The design and ethical parameters of the study were approved by Institutional Review Board of DUHS, Karachi (Ref: IRB-1143/DUHS/Approval/2018/). Informed consent was attained by all study participants above 18 years of age. Under-aged patients such as children or individuals who were under the age of 18 were included with signed consent from parents and guardians. Anonymity of the data was safeguarded to preserve the privacy of the records. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Autologous hematopoietic cell transplantation (AHCT) is a commonly used treatment in multiple myeloma (MM). However, real-world global demographic and outcome data are scarce. We collected data on baseline characteristics and outcomes from 61 725 patients with newly diagnosed MM who underwent upfront AHCT between 2013 and 2017 from nine national/international registries. The primary endpoint was overall survival (OS), and the secondary endpoints were progression-free survival (PFS), relapse incidence (RI) and non-relapse mortality (NRM). Median OS amounted to 90.2 months (95% CI 88.2-93.6) and median PFS 36.5 months (95% CI 36.1-37.0). At 24 months, cumulative RI was 33% (95% CI 32.5%-33.4%) and NRM was 2.5% (95% CI 2.3%-2.6%). In the multivariate analysis, superior outcomes were associated with younger age, IgG subtype, complete hematological response at auto-HCT, Karnofsky score of 100%, international staging scoring (ISS) stage 1, HCT-comorbidity index (CI) 0, standard cytogenetic risk, auto-HCT in recent years, and use of lenalidomide maintenance. There were differences in the baseline characteristics and outcomes between registries. While the NRM was 1%-3% at 12 months worldwide, the OS at 36 months was 69%-84%, RI at 12 months was 12%-24% and PFS at 36 months was 43%-63%. The variability in these outcomes is attributable to differences in patient and disease characteristics as well as the use of maintenance and macroeconomic factors. In conclusion, worldwide data indicate that AHCT in MM is a safe and effective therapy with an NRM of 1%-3% with considerable regional differences in OS, PFS, RI, and patient characteristics. Maintenance treatment post-AHCT had a beneficial effect on OS., (© 2024 The Author(s). American Journal of Hematology published by Wiley Periodicals LLC.)

In recent decades, there has been considerable interest in investigating advanced energetic materials characterized by high stability and favorable energetic properties. Nevertheless, reconciling the conflicting balance between high energy and the insensitivity of such materials through traditional approaches, which involve integrating fuel frameworks and oxidizing groups into an organic molecule, presents significant challenges. In this study, we employed a promising method to fabricate high-energy-density materials (HEDMs) through the intermolecular assembly of variously substituted purines with a high-energy oxidant. Purines are abundant in nature and are readily available. A series of advanced energetic materials with a good balance between energy and sensitivity were prepared by the simple and effective self-assembly of purines with high-energy oxidants. Notably, these compounds exhibit incredibly improved crystal densities (1.80-2.00 g·cm -3 ) and good detonation performance ( D : 7072-8358 m·s -1 ; P : 19.82-34.56 GPa). In comparison to RDX, these self-assembled energetic materials exhibit reduced mechanical sensitivities and enhanced thermal stabilities. Compounds 1 - 5 demonstrate both high energy and low sensitivity, indicating that self-assembly represents a straightforward and effective approach for developing advanced energetic materials with a balanced combination of energy and safety. Moreover, this study offers an avenue for synthesizing energetic materials based on naturally occurring compounds assembled through intermolecular attractions, thereby achieving a balance between energy and sensitivity along with versatile functionality.

The eighth workshop of the Worldwide Network for Blood and Marrow Transplantation (WBMT) was held in Islamabad, Pakistan, from September 22 to 23, 2022, aiming to foster hematopoietic stem cell transplant (HSCT) activity in the World Health Organization (WHO) Eastern Mediterranean Region (EMRO). Participating countries, including Pakistan, Oman, Iran, and Saudi Arabia, reported increased HSCT in the last few years, whereas others from the EMRO and beyond, including Qatar, United Arab Emirates, Nepal, and Bangladesh, started HSCT recently and have developed HSCT programs with excellent results. During educational sessions and open dialog, participating teams and international experts from the WBMT shared their experience and discussed minimum essential requirements for establishing and expanding HSCT in emerging countries, indications for HSCT training and dissemination of knowledge, stem cell donor selection and safety, quality assurance in transplant centers, and the value and importance of transplant outcome databases. International support, collaboration, and local engagement, including government participation and WHO assistance, are valuable in increasing HSCT access worldwide., (Copyright © 2024 Hematology/Oncology and Stem Cell Therapy.)

Tetrazoles and their derivatives are essential for compound synthesis due to their versatility, effectiveness, stability in air, and cost-efficiency. This has stimulated interest in developing techniques for their production. In this work, four compounds, tetrazolo[1,5- c ]pyrimidin-5-amine ( 1 ), N-(4-azidopyrimidin-2-yl)nitramide ( 2 ), tetrazolo[1,5- c ]pyrimidin-5(6H)-one ( 3 ), and tetrazolo[1,5- a ]pyrimidin-5-amine ( 4 ), were obtained from commercially available reagents and straightforward synthetic methodologies. These new compounds were characterized by infrared (IR), 13 C, and 1 H NMR spectroscopy, differential scanning calorimetry (DSC), and single-crystal X-ray diffraction. The solvent, temperature, and electron-donating group (EDG) factors that were responsible for the steering of azido-tetrazole equilibrium in all compounds were also studied. In addition, the detonation performance of the target compounds was calculated by using heats of formation (HOFs) and crystal densities. Hirshfeld surface analysis was used to examine the intermolecular interactions of the four synthesized compounds. The results show that the excellent properties of 1 - 4 are triggered by ionic bonds, hydrogen bonds, and π-π stacking interactions, indicating that these compounds have the potential to be used in the development of high-performance energetic materials. Additionally, DFT analysis is in support of experimental results, which proved the effect of different factors that can influence the azido-tetrazole equilibrium in the synthesized pyrimidine derivatives in the solution.

Hematopoietic stem cell transplant (HSCT) is potentially, the sole curative option for many malignant and non-malignant hematological disorders. Finding a human leukocyte antigen (HLA) compatible donor remains one of the limiting factors, hampering the utilization of HSCT. However, the introduction of post-transplant cyclophosphamide (PTCy) has improved the outcomes of haploidentical transplants making it a suitable option for patients lacking HLA-compatible donors. We collected data from 44 patients who underwent haplo-identical allogeneic stem cell transplants at the Armed Forces Bone Marrow Transplant Center/National Institute of Blood and Marrow Transplant (AFBMTC/NIBMT) from the year 2015 to 2022. The diseases were divided into three categories, i.e., bone marrow failure (BMF) syndromes, hematological malignancies (HM) and miscellaneous (Misc) groups. Median age at transplant was 18 (01-39) years. Transplant indications included aplastic anemia (AA) in 21 (47.7%) cases, 15 (34.1%) HM, and eight (18.2%) cases falling in the Misc groups. A maximum number of graft failures occurred in the BMF group; primary graft failure in 07 (33.3%) cases and secondary graft failure in four (19%) cases, (p-value < 0.05). Acute graft versus host disease (aGVHD) grade II-IV occurred in nine (20.5%) cases while chronic graft versus host disease (cGVHD) occurred in 10 (22.7%) cases. Cytomegalovirus (CMV) reactivation was seen in 31 (70.5%) cases. Maximum CMV reactivation was seen in HM group 13 (86.6%) cases, (p-value < 0.05) as compared to BMF (71.4%) and Misc groups (37.5%). Post-transplant cyclophosphamide (PTCy) based regimens, early neutrophil engraftment, and patients with GVHD had better survival outcomes (p-value < 0.05) overall survival (OS), and relapse-free survival (RFS). and GVHD-free relapse-free survival (GFRS) were significantly better in cases with early neutrophil engraftment. OS of the study cohort was 50% while disease-free survival (DFS) and GFRS were 45.5% and 36.4%, respectively., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Akram et al.)

Objective: To compare donor graft characteristics and clinical outcomes in recipients of allogeneic heamatopoietic stem cell transplantation (HSCT) using GCSF primed bone marrow (GBM) and steady-state bone marrow (SBM) as stem cell sources., Study Design: Observational study. Place and Duration of the Study: Department of Clinical Haematology, Armed Forces Bone Marrow Transplant Centre, Rawalpindi, Pakistan, from August 2018 to October 2020., Methodology: Eighty patients undergoing allogeneic HSCT were analysed. Among these, forty each received GBM and SBM from HLA identical siblings. Graft characteristics, such as total nucleated cells, CD34+ cell yield; clinical outcomes such as neutrophil and platelet engraftment, primary and secondary graft failure (GF), as well as the frequency of acute and chronic graft versus host disease (GvHD), were recorded and compared using the t-test, with significance at p <0.05., Results: A statistically significant difference was observed in CD34+ dose with median dose 7.68 (p=0.002) but not in TNC dose with meadin dose 5 (p=0.86). Neutrophil engraftment occurred much more quickly with median of 13.43 days in the GBM than SBM group (p=0.025). While no statistically significant difference (p=0.89) in platelet engraftment was reported in both SBM and GBM. At the same time, patients with both GBM and SBM transplants showed a comparable ratio of acute to chronic GvHD and primary to secondary GF., Conclusion: GBM is associated with better CD34+ stem cell yield and quicker neutrophil engraftment in clinical outcomes., Key Words: Granulocyte colony-stimulating factor, Bone marrow, Hematopoietic stem cell transplantation.

The construction and design of pyrotechnics with superior performance is not only a task of great significance but also a tremendous challenge. In this regard, we present the syntheses of novel green primary colors pyrotechnics (red, green, and blue light-generating pyrotechnics) by employing 4-chloro-3,5-dinitropyrazole (CDNP) as a multifunctional raw material. CDNP contains a flame enhancer, oxygen-rich functional group, and nitrogen heterocyclic combustibles, which contribute to the high performance of the pyrotechnics. The characteristic elements (strontium, barium, and copper) that impart color to the flame are combined with the CDNP to synthesize the primary colors pyrotechnics by an "all-in-one" strategy. The structures of three energetic metal salts ( EMS-1 , EMS-2 , and EMS-3 ) are completely characterized, and their thermal stability, sensitivity, ignition performance, and color purity are systematically evaluated. All EMSs show excellent thermal stability and low mechanical sensitivities (>330 °C, >40 J, >360 N). Moreover, the EMSs demonstrate successful ignition and combustion under laser conditions and roasting test conditions, producing bright characteristic flames. Chromaticity analysis reveals that the three EMSs possess good color purities of 91, 80, and 70%, respectively. Consequently, the three integrated pyrotechnics exhibit exceptional combustion properties, highlighting their potential for use in various pyrotechnic applications.

Cytomegalovirus (CMV) infection is a major cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Limited data are available from developing countries regarding the frequency of CMV infection and treatment outcomes. We enrolled 230 consecutive patients undergoing allogeneic HSCT for various hematologic disorders at the Armed Forces Bone Marrow Transplant Center/National Institute of Blood And Marrow Transplant between February 2017 and December 202. CMV reactivation post-HSCT was monitored weekly starting at day +30 and continuing until day +100, and preemptive antiviral therapy was administered to prevent CMV disease in all HSCT recipients with ≥2000 CMV copies/mL. The median age of the study cohort was 9.5 years (range, .6 to 53 years), and the male:female ratio was 2.4:1. The most frequent indication for HSCT was beta thalassemia major (36.1%), followed by aplastic anemia (23.9%). Malignant disorders constituted 20% of all the patients. Pretransplantation CMV seropositivity was 99.1% for the recipients and 99.5% for the donors. CMV infection was seen in 66.1% of the patients, and the median time to CMV DNAemia was 36 days (range, 12 to 95 days). Preemptive antiviral therapy was administered to 140 patients with a CMV viral load ≥2000 copies/mL (61%). In multivariate analysis, patient age >12 years, steroid administration, and use of mycophenolate mofetil with or without post-transplantation cyclophosphamide was associated with the greatest probability of CMV reactivation. Overall survival was 97.4% in patients without CMV reactivation, compared to 80.3% in those with CMV reactivation (P = .001). Event-free survival was 78.7% in the total study cohort, including 89.7% for patients without CMV reactivation and 73% for patients with CMV reactivation (P = .003). Our study is the first from this region to explore the frequency of CMV seropositivity and CMV infection, risk factors for CMV reactivation, and outcomes of antiviral therapy in HSCT recipients., (Copyright © 2023 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: Aplastic anaemia is a rare bone marrow failure syndrome and is defined by pancytopenia associated with a hypo-cellular bone marrow with no increase in reticulin and the absence of any abnormal infiltrate. The objective of the study was to determine the frequency of Aldehyde Dehydrogenase type 2 (ALDH2) deficiency in patients with Aplastic Anaemia and investigate its correlation with patient and disease characteristics. It was a descriptive cross-sectional study conducted at Armed Forces Bone Marrow Transplant Centre Rawalpindi from 01-08-2022-01-02-2023, over 6 months., Methods: A total of 56 patients who were diagnosed with aplastic anaemia during this period, fulfilling inclusion criteria were enrolled. Patients were genotyped as GG (homozygous) and GA (heterozygous). GG had normal ALDH2, while GA were patients with ALDH2 deficiency. Data was collected on the patient's demographics, type and severity of anaemia, type of hematopoietic stem cell transplant (HSCT) and frequency of ALDH2 deficiency. Results were analyzed for ALDH2 deficiency and its correlation with patient and disease characteristics was investigated., Results: A total of 56 patients were included in the study. The median age of the patients was 28 years (20-39). According to the type of aplastic anaemia, 2 (3.6%) had Fanconi anaemia and 54 (96.4%) had acquired aplastic anaemia. In our study, 18 (32.1%) patients had undergone HSCT while the remaining 38 (67.9%) could not undergo HSCT. The frequency of the presence of ALDH2 deficiency was 2 (3.6%). There was no statistically significant correlation between the frequency of ALDH2 deficiency with variables like gender, age distribution, type of aplastic anaemia, the severity of aplastic anaemia and hematopoietic stem cell transplant., Conclusions: We concluded from our study the frequency of ALDH2 was rare in patients with aplastic anaemia. There was no statistically significant correlation between the frequency of ALDH2 deficiency with variables like gender, age distribution, type of aplastic anaemia, the severity of aplastic anaemia and hematopoietic stem cell transplant.

The World Health Organization-designated Eastern Mediterranean region (EMRO) consists of 22 countries in North Africa and Western Asia with a collective population of over 679 million. The area comprises some of the wealthiest countries per capita income and some of the poorest. The population structure is also unique and contrasts with western countries, with a much younger population. The region sits in the heart of the thalassemia belt. Many countries have a significant prevalence of sickle cell disease, and cancer is on the rise in the region. Therefore, the strategic priorities for the growth and development of hematopoietic stem cell transplantation (HSCT) differ from country to country based on resources, healthcare challenges, and prevalent infrastructure. Thirty-one reporting teams to the Eastern Mediterranean Blood and Marrow Transplantation Group have active HSCT programs in 12 countries; allogeneic transplants outnumber autologous transplants, and the proportion of allotransplants for non-malignant conditions is higher in the EMRO region than in Western Europe and North America. The vast majority (99%) of allotransplants are from matched related donors. Matched unrelated donors and other alternate donor transplants are underutilized. The chance of finding a matched related donor for allografts is higher, with a significant chance of finding matched donors among non-sibling related donors. Reasons for relatively lower rates of transplants compared with other countries are multifactorial. Capacity building, development of newer centers, innovative funding, and better utilization of information technology are required to make transplantation as an accessible modality to more patients. Cost-effectiveness and cost-containment, regulation, and ensuring quality will all be priorities in planning HSCT development in the region.

Dyskeratosis congenita (DKC), also known as Zinsser-Cole-Engman syndrome, is a telomeropathy typically presenting as a triad of leukoplakia, nail dystrophy, and reticular hyperpigmentation. Reported genetic mutations linked to DKC include DKC1 , TINF2 , TERC , TERT , C16orf57 , NOLA2 , NOLA3 , WRAP53/TCAB1 , and RTEL1 . Homozygous, compound heterozygous, and heterozygous mutations in RTEL1 ( RTEL1 , regulator of telomere elongation helicase 1) gene on chromosome 20q13 are known to cause autosomal dominant as well as recessive DKC. Pathogenic variants of RTEL1 gene in DKC patients include c.2288G>T (p. Gly763Val), c.3791G>A (p. Arg1264His), and RTEL p. Arg981Trp. We report a novel homozygous variant of RTEL1 , transcript ID: ENST00000360203.11, exon 24, c.2060C>T (p.Ala687Val), in a patient of DKC presenting with leukoplakia, dystrophic nails, reticulate pigmentation, and positive family history of a similar phenotype. The novel variant, reported as a variant of uncertain significance, may therefore be considered diagnostic for DKC in a Pakistani population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Nisar, Khan, Chaudhry, Iftikhar and Ghafoor.)

Background: Aplastic Anaemia (AA) is characterized by pancytopenia and hypocellular marrow. Immunosuppressive therapy (IST) SHOWS impressive haematological response; however, risk of relapse and clonal evolution persists. The objective of the study is to assess response to IST in patients with aplastic anaemia., Methods: A retrospective single centre study at AFBMTC / NIBMT for patients of acquired AA was conducted from January 2005 to December 2019.Inclusion criteria included diagnosed cases of acquired AA receiving IST for at least 12 weeks and age >2 years. IST included cyclosporine (CsA) alone, CsA + androgens, CsA + rabbit anti thymocyte globulin (rATG), CsA + horse anti thymocyte globulin (hATG). Primary outcome measure was response to IST; secondary outcome measure was overall survival (OS)., Results: A total of 513 patients received IST. Median age was 23 years (range 2-97 years). In study cohort, 155 (30.2%) patients responded to the IST, 63 (12.3%) achieved complete response (CR) while 92 (17.9%) achieved partial response (PR). The ORR of CsA in NSAA, SAA and VSAA was 52.6%, 28.10% and 10% respectively; whereas ORR of CsA + rATG in NSAA, SAA and VSAA was 50%, 35.1% and 22.5% respectively. OS was 38% at a median follow up of 36 months. There was a significant difference in the survival distributions of different treatment modalities (p=0.016). Median survival time 60 months (CsA), 9 months (CsA+ androgens) and 39 months (CsA+ rATG/hATG.) ., Conclusion: In resource constrained settings, single agent CsA remains a reasonable alternative with modest activity and acceptable side effect profile.

Background: Acute promyelocytic leukaemia (APL) characterized by t (15;17) leading to formation of fusion protein PML-RARA is an acute leukaemia with highest mortality. A remarkable improvement in the outcomes has been witnessed due to evolution of highly effective targeted therapies replacing the traditional chemotherapy is most patients. However limited data is available regarding treatment outcomes of APL using various novel regimens from developing countries like Pakistan., Methods: This was a retrospective descriptive study which included APL patients treated at AFBMTC Rawalpindi from 2005 to 2020. It included a total of 51 eligible patients with a diagnosis of de novo APL confirmed by the presence of PML-RARA transcript or presence of t (15;17) by cytogenetics or FISH analysis. The protocols used for treatment included the UKAML MRC 12, the LPA-99/LPA-2005 PETHEMA, the APML4 and non-chemotherapy based ATO-ATRA protocol., Results: The study included 51 patients in which 31 (60.78%) were male and 20 (39.2%) were female. The median age at diagnosis was 30 years (range 5-70). The commonest symptom was fever seen in 43 (84.3%) patients and bruising was the commonest physical finding present in 44 (86.3%) patients. High-risk patients were 23 (46.1%), 18 (35.3%) were intermediate risk and 10 (19.6%) were low risk. The LPA99/LPA2005 was most frequently employed protocol being used in 36 (72%) patients. There were 2 deaths during induction and 44 (86.3%) achieved CR post induction. The median follow up time was 32 months (range 1 to 190 months) with an overall survival (OS) of 76.5% and a relapse free survival (RFS) of 66.7., Conclusions: Our study shows APL is a highly curable malignancy and outcomes have improved with newer non chemotherapy based therapies. It can also be concluded that outcomes of APL gradually improved over the past 2 decades due to improvement in supportive care, provision of blood products and use of newer protocols. The prognosis remains less favourable in high risk patients.

Background: Hairy cell leukaemia (HCL) is an uncommon neoplasm of mature B-lymphoid cells which is characterized by cytopenias, commonly of all three cell lines, with typical hairy cells on peripheral smear and/or bone marrow along with organomegaly. Objective was to document the outcomes of HCL patients treated at a tertiary care hospital in Pakistan., Methods: Medical records of patients from 2004 to 2020 were reviewed and data was collected to assess patient's demographics, symptomatology, remission rate and overall survival. The record flies of all patients presenting to AFBMTC with HCL were included in the study. The record file with insufficient data were excluded., Results: 26 patients with a mean age of 48.12±11.43 years were diagnosed with HCL and treated at AFBMTC. Out of these, 23 (88.4%) were male and 03 (11.5%) females. The main presenting complaints were generalized body aches (34.6%), fever (15.4%), incidental finding of cytopenias (11.5%) and abdominal discomfort (26.9%). Splenomegaly was found in 76.92% while hepatomegaly was found in 46.15% of patients. A total of 12 (46.15%) patients received Cladribine (either intravenous or subcutaneous) and splenectomy was done in 7 (26.92%) as 1st line treatment. Eleven patients out of 12 (83.33%) who received Cladribine and 05 (71.42%) patients out of seven who underwent splenectomy; achieved complete remission (CR) after 1 st line of treatment. One patient received Cladribine as 1st line of treatment but did not respond and CHOP regimen was given as second line. Out of the 26 patients, 5 patients (19.23%) relapsed at a median interval of 5.83±6.6 years. Two patients received Cladribine + Rituximab while 03 patients received cladribine as their salvage therapy. Disease free survival (DFS) of 71.4% among the patients underwent splenectomy while 75.0% among the patients received Cladribine. DFS for combination therapy (included CHOP and CVP) was 66.7% while OS was calculated among patients who received cladribine, splenectomy and combination chemotherapy as 100%, 85.7%, 66.7% respectively., Conclusions: Cladribine has a significant efficacy and encouraging acute and long-term benefits when administered to patients with HCL. A single course of cladribine was able to induce CR in a vast majority of patients. At a median follow up of 4.6 years the OS was 100% with cladribine and 85% with splenectomy. Those who relapsed were successfully retreated with cladribine + Rituximab.

Aplastic anemia is a relatively rare but potentially fatal disorder, with a reported higher incidence in developing countries in comparison to the West. There are significant variations in epidemiological as well as etiological factors of bone marrow failure syndromes in the developing countries in comparison to the developed world. Furthermore, the management of bone marrow failure syndromes in resource constraint settings has significant challenges including delayed diagnosis and referral, limited accessibility to healthcare facilities, treatment modalities as well as limitations related to patients who require allogeneic stem cell transplantation. Here we will provide a review of the available evidence related to specific issues of aplastic anemia in the developing countries and we summarize suggested recommendations from the Eastern Mediterranean blood and bone marrow transplantation (EMBMT) group and the severe aplastic anemia working party of the European Society of blood and marrow transplantation (SAAWP of EBMT) related to the diagnosis and therapeutic options in countries with restricted resources., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise., Competing Interests: Munira MoosajeeTravel, Accommodations, Expenses: Roche Kamran RashidHonoraria: Roche/GenentechSpeakers' Bureau: Roche/Genentech, Lilly MedicalTravel, Accommodations, Expenses: Roche Usman AhmadHonoraria: RocheTravel, Accommodations, Expenses: RocheNo other potential conflicts of interest were reported.

Background: Coronavirus disease 2019 (COVID-19) is a multisystem disorder and haematological abnormalities are frequently documented in affected patients., Methods: This retrospective study included 549 patients hospitalized with COVID-19 from 1st June to 15th July 2020 at Pak Emirates hospital, Rawalpindi Pakistan. p<0.05 was considered statistically significant., Results: Median age was 60 years (range 12-94 years), males 442 (80.5%) and females 107 (19.5%). There was no patient with mild illness, 181 (32.9%) had moderate, 158 (28.7%) severe and 210 (38.2%) patients had critical disease. Patients with severe and critical disease had lower absolute lymphocyte count (ALC) and platelets (p<0.001 for both) while higher white blood cell count (WBC), neutrophil lymphocyte ratio (NLR), C-reactive protein (CRP), interleukin-6 (IL-6) and lactate dehydrogenase levels (LDH) levels (all p<0.001). Overall survival of study cohort was 83.2% (n=457). Median haemoglobin and platelet count were significantly lower (p<0.001) while WBC, ANC, NLR, prothrombin time (PT), activated partial thromboplastin time (APTT), ferritin, IL-6, LDH were significantly higher (p<0.001) for patients who died. On multivariate logistic regression analysis WBC count>10x109/l (odds ratio [OR] 2.19 [95% CI 1.3-4.2] p=0.01), NLR>9 (OR 3.4 [95% CI 0.87-6.8], p<0.001), platelets<150x109/l (OR 3.9 [95% CI 1.4-9.8] p<0.001), CRP >100; (OR 4.1[95% CI 0.78-10.9] p<0.001) and ferritin >1000 (OR 5.3 [95% CI 1.9- 13.5], p<0.001) were associated with increased risk of death in patients with COVID-19., Conclusion: Monitoring of haematological, coagulation and inflammatory parameters provide reliable, convenient, rapid and cost-effective method for predicting disease severity, complications and prognosis of COVID-19 patients.

Management of rare hematological disorders pose unique diagnostic and therapeutic challenges due to unusual occurrence and limited treatment options. We retrospectively identified 45 patients receiving matched related donor transplant for rare hematological disorders from 2006 to 2019. Patients were divided into two groups (1) malignant and (2) non malignant. The malignant disorder group included four patients while the nonmalignant group included 41 patients divided into immune dysregulation (n = 23), bone marrow failure (n = 10), metabolic (n = 5), and bleeding diathesis (n = 3). Twenty-six (57.8%) patients received myeloablative conditioning (MAC) and 16 (35.6%) received reduced intensity conditioning (RIC), while 3 (6.6%) patients with severe combined immunodeficiency received stem cell infusion alone without conditioning. The cumulative incidence (CI) of grade II-IV acute GVHD (aGVHD) was 39.1% (n = 18) and chronic GVHD (cGVHD) 15.2% (n = 7). There was no primary graft failure while CI of secondary graft failure was 9%. Overall survival (OS) and disease-free survival (DFS) was 82.2% and 77.8% respectively. Group wise OS was 75% in the malignant group, 82.6% in the immune dysregulation group, 80% in patients with metabolic disorders and bone marrow failure, while 100% in patients with bleeding diathesis. This retrospective analysis shows that hematopoietic stem cell transplant can be a feasible treatment option for rare hematological disorders.

Cyclosporine (CsA) combined with short-course methotrexate is considered standard-of-care graft-versus-host disease (GVHD) prophylaxis for patients with severe aplastic anemia (AA) who undergo transplantation using cyclophosphamide (Cy) plus anti-thymocyte globulin (ATG) conditioning. However, there is no consensus on optimal post-transplant GVHD prophylaxis for patients undergoing matched related donor (MRD) transplantation using fludarabine (Flu)-based conditioning. We conducted a single-center retrospective analysis of patients with acquired AA (n = 106) undergoing MRD transplantation from July 2007 through January 2019. All patients received Flu-Cy-ATG conditioning and single-agent CsA as GVHD prophylaxis. Median age of the study cohort was 20 years (range, 3 to 52) and male to female ratio was 3.8:1. Median time from diagnosis to transplant was 11.5 months (range, 2.8 to 62). Graft source was bone marrow harvest in 71 (68%), combined bone marrow and peripheral blood stem cells in 34 (31%), and peripheral blood alone in 1 (1%) patient. Cumulative incidence of neutrophil engraftment at day 28 was 93.4% (95% confidence interval [CI], 87.3% to 97.1%) while that of platelet engraftment at day 100 was 90.5% (95% CI, 84% to 96%). Cumulative incidence of primary graft failure at day 28 was 6.6% (95% CI, 4% to 8%) while secondary graft failure occurred at a median of 190 days (range, 90 to 415) at a cumulative incidence of 3.7% (95% CI, 2% to 5%). Cumulative incidence of grade II to IV acute GVHD at day 100 was 3.8% (95% CI, 1.4% to 9.9%), while a 1-year probability of chronic GVHD was calculated as 7.5% (95% CI, 2.6% to 15%). Median follow-up post-transplant was 61 months (range, 6 to 144). Overall survival was 84.9%, disease-free survival was 80.2%, and GVHD-free relapse-free survival was 76.3%. This study indicates that single-agent cyclosporine is a feasible option for GVHD prophylaxis in MRD hematopoietic stem cell transplantation using Flu-Cy-ATG conditioning and is associated with very low rates of acute and chronic GVHD., (Copyright © 2020 American Society for Transplantation and Cellular Therapy. All rights reserved.)

Allogeneic stem cell transplant for high-risk aplastic anemia (AA) yields inferior results using conventional cyclophosphamide (CY)-based conditioning. The use of fludarabine (Flu)-based regimens has resulted in improved outcomes in high-risk patients. Limited data are available comparing these two conditioning regimens in such patients. We retrospectively analyzed 192 high-risk patients undergoing matched-related donor transplantation from July 2001 to December 2018. The median age was 19.5 (2-52) years. Patients were divided into 2 groups, Cy 200 anti-thymocyte globulin (ATG) 20 (Gp1 n = 79) or Flu 120-150 Cy 120-160 ATG 20 (Gp2 n = 113). The risk of graft failure was significantly higher in Gp1, and the majority occurred in patients with >2 risk factors ( p = 0.02). The incidence of grade II-IV acute graft versus host disease (GVHD) and chronic GVHD was not significantly different between the two groups. The overall survival (OS) of the study cohort was 81.3 %, disease-free survival (DFS) 76.6 % and GVHD-free relapse-free survival (GRFS) was 64.1%. DFS and GRFS were significantly higher in Gp2 as compared to Gp1: DFS 84.1% versus 68.4 % ( p = 0.02), GRFS 77.9% versus 54.4% ( p = 0.01), respectively. We conclude that Flu-based conditioning is associated with superior OS, DFS and GRFS as compared to the conventional Cy-based regimen in high-risk AA., Competing Interests: This manuscript contains original research not previously published or submitted for publication elsewhere while under consideration. The authors declare no conflict of interest with this manuscript., (© 2020 International Academy for Clinical Hematology. Publishing services by Atlantis Press International B.V.)

Despite excellent transplant outcomes of aplastic anemia (AA) in developed countries, management in developing countries is challenging because of delay in the diagnosis, use of family donors for transfusions, and higher infection risk pretransplant. These factors can lead to allo-immunization, increased risk of graft failure, graft-versus-host disease (GVHD), and transplant-related mortality, leading to unfavorable outcomes. Conventional cyclophosphamide (Cy) and antithymocyte globulin (ATG) are associated with inferior overall survival in such high-risk patients. We conducted single-center retrospective analysis of high-risk AA patients (N = 147) enrolled consecutively and undergoing matched related donor transplant from March 2002 through October 2018. We included high-risk AA patients receiving fludarabine (Flu)-based conditioning. Median patient age was 20 years (range, 3 to 52). The median time from diagnosis to transplant was 11 months (range, 3 to 63). High-risk features included age ≥ 20 years in 55.8% of patients (n = 82), disease duration more than 3 months in 95 % (n = 140), RBC concentrates transfusions > 20 in 79.6% (n = 117), random donor platelet transfusion > 50 in 64.6% of patients (n = 95), and second hematopoietic stem cell transplant (HSCT) in 7.4% (11). We divided patients into 2 groups based on different conditioning regimens. Flu group 1 (Flu1) received Flu 120 to 150 mg/m 2 , Cy 120 to 200 mg/kg, and ATG 20 mg/kg, and Flu group 2 (Flu2) was given Flu 150 mg/m 2 , Cy 300 mg/m 2 , and ATG 20 mg/kg. Bone marrow stem cells were used as graft source in 97% of patients (n = 144) (alone in 52% and with peripheral blood stem cells in 45%). Cyclosporine alone was used for GVHD prophylaxis in 75% (n = 110) and cyclosporine plus methotrexate in 25% (n = 37). Median total nucleated cell dose was 5 × 10 8 /kg. Median days for neutrophil engraftment was 13 (range, 10 to 20) and platelet engraftment 20 (range, 14 to 43). Day 100 mortality was 7.5% (n = 11). Sustained successful engraftment was achieved in 87.8% of patients (n = 129). Most graft failures (40%) occurred in Flu2 conditioning (P = .000) and in patients with >2 risk factors (P = .000). Overall incidence of acute and chronic GVHD was 11.6% (n = 17) and 12.9% (n = 19), respectively, in Flu1 and Flu2 groups. Overall survival (OS), disease-free survival (DFS), and GVHD-free relapse-free survival (GRFS) was 83.7%, 78.2%, and 70.7%, respectively. A trend toward improved OS was observed in patients receiving Flu1 conditioning but was statistically nonsignificant (P = .256), whereas DFS and GRFS were significantly better in Flu1 versus Flu2 (P = .004 and .001, respectively). When stratified per number of risk factors (age > 20, RBC concentrate > 20 or platelet > 50 random, duration > 3 months, previous HSCT), OS and DFS decreased significantly with increasing number of risk factors (P = .000 and .001, respectively). Patients are able to tolerate Flu-based conditioning well with lower rates of rejection and excellent long-term survival in high-risk AA patients. Cyclosporine alone as GVHD prophylaxis and marrow source stem cells as graft source are preferable options. Use of Flu plus low-dose Cy conditioning is associated with inferior survival outcomes. A randomized trial of Flu-based versus conventional Cy-containing conditioning would be helpful in establishing a standard of care conditioning regimen in high-risk AA patients., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. All rights reserved.)

Xanthenone based hydrazone derivatives (5a-n) have been synthesized as potential α-glucosidase inhibitors. All synthesized compounds (5a-n) are characterized by their FTIR, 1 H NMR, 13 C NMR and HRMS, and in case of 5g also by X-ray crystallographic technique. The compounds unveiled a varying degree of α-glucosidase inhibitory activity when compared with standard acarbose (IC 50  = 375.38 ± 0.12 µM). Amongst the series, compound 5l (IC 50  = 62.25 ± 0.11 µM) bearing a trifluoromethyl phenyl group is found to be the most active compound. Molecular modelling is performed to establish the binding pattern of the more active compound 5l, which revealed the significance of substitution pattern. The pharmacological properties of molecules are also calculated by MedChem Designer which determines the ADME (absorption, distribution, metabolism, excretion) properties of molecules. The solid state self-assembly of compound 5g is discussed to show the conformation and role of iminoamide moiety in the molecular packing., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Patients with haematological malignancies and stem cell transplant recipients are at high risk of opportunistic infections. Little international and no national data is available comparing noble metal coated versus uncoated central venous catheters (CVC) in this special population of severely immunocompromised patients. Objective of the study is to compare infectious and non-infectious complications of noble metal coated versus uncoated central venous catheters in patients undergoing stem cell transplantation and receiving chemotherapy for acute myeloid leukaemia., Methods: This is a prospective, cross-sectional, randomized study (January to December 2016), enrolling 45 consecutive patients undergoing stem cell transplantation or chemotherapy for acute myeloid leukaemia. Patients were randomized in 2 groups. Twenty 23 patients received standard CVC and 22 patients received CVC catheters coated with three noble metals (Gold, Silver, Palladium). Patients were observed for catheter related infectious and noninfectious complications. Data was analysed using SPSS., Results: Mean age was 24.3 (±4.91) in uncoated and 25.09 (±5.22) in coated CVL group. CRBSI infection was detected in 2 (8.6%) and 3 (13.6%) patients in uncoated and coated group respectively with p-value of .279. There was no statistically significant difference in febrile episodes between coated (95.4%) and uncoated (91.3%) group. While we considered non-infectious complications, 2 patients in coated (8.6%) and 1 in uncoated CVCs group (4.3%) had CVC thrombosis which was not significant statistically., Conclusion: There was no efficacy of BG-thin noble metal coated CVCs in reducing infectious and non-infectious complications (thrombosis) in our study.

A 42 years old male with relapsed diffuse large B-cell lymphoma was given second-line chemotherapy followed by reduced intensity allogeneic stem cell transplantation from HLA matched brother. Twelve weeks posttransplant, his disease relapsed evidenced by the appearance of lymphoma cells in the peripheral blood and declining donor chimerism. Donor lymphocyte infusion was given that induced complete lymphoma remission. The patient is well 3 years posttransplant with his disease in complete remission.

Neurological complications are quite frequent in stem cell transplant (SCT) recipients. Major causes are conditioning regimen toxicity, metabolic and electrolyte disturbances, viral infections and cyclosporine related toxicity. Cyclosporine induced neurotoxicity is a well documented complication in stem cell transplant recipients. These patients usually present with seizures which are easily controlled with anti-convulsants and by reducing/withholding the drug. However uncontrolled seizures requiring ventilatory support are rarely reported. Here we present a case report of cyclosporine induced uncontrolled seizures in a young female after allogeneic SCT which was unresponsive to anti-convulsive therapy but was successfully treated with mechanical ventilatory support.

Mycobacterium tuberculosis is a serious, but rare infectious complication after allogeneic bone marrow transplantation. Tuberculosis is a major problem in South East Asia, particularly in India and Pakistan. We describe here infection due to mycobacterium tuberculosis in four patients after allogeneic stem cell transplantation (Allo SCT). The diagnosis was made on the bases of clinical findings, sputum / blood / pleural and pericardial fluids / broncho alveolar lavage (BAL) and tissue biopsy examination. Anti tuberculosis therapy (ATT) was started immediately after diagnosis. Three patients responded to antituberculosis therapy, where as one patient developed severe infective respiratory complications and died at six months post transplant. Mycobacterial infection should be considered in patients post allo SCT with unexplained fever, cough or pleuritic chest pain. These patients at diagnosis should be promptly treated with ATT.