Long-term real-world outcomes of patients with acute promyelocytic leukaemia treated with arsenic trioxide and all-trans retinoic acid without chemotherapy-a retrospective, single-centre study.

Arsenic trioxide (ATO) and all-trans retinoic acid (ATRA) form the backbone of the treatment of acute promyelocytic leukaemia (APL), with the addition of chemotherapy for high-risk patients. We describe our experience of treating patients with APL of all risk classes with ATO and ATRA without chemotherapeutic agents. Patients received induction with ATO and ATRA followed by three cycles of consolidation with ATO and ATRA (each 1 month apart) after achieving morphological remission. Patients with intermediate- and high-risk disease received a further 2 years of maintenance with ATRA, 6-mercaptopurine and methotrexate. A total of 206 patients were included in the study. The majority of the patients were intermediate risk (51.9%), followed by high risk (43.2%). Differentiation syndrome was seen in 41 patients (19.9%). Overall, 25 patients (12.1%) died within 7 days of initiating therapy. Seven patients relapsed during follow-up. The mean (SD) estimated 5-year event-free survival (EFS) and overall survival (OS) in the entire cohort was 79% [5.8%] and 80% [5.8%] respectively. After excluding patients who died within 7 days of therapy initiation, the mean (SD) estimated 5-year EFS and OS was 90% [5.8%] and 93% [3.9%] respectively. Our study shows that treatment of all risk classes of APL with ATO and ATRA without chemotherapy is associated with excellent long-term outcomes in the real-world setting.

Characteristics and outcome of infectious complications after autologous hematopoietic cell transplantation in multiple myeloma patients.

BACKGROUND: Infections are a significant cause of morbidity and mortality after autologous hematopoietic cell transplantation (AHCT) in multiple myeloma (MM) patients. There has been a rapid advancement and evolution in MM treatment landscape in the last decade. There is limited information on post-AHCT infectious complications among MM patients with or without levofloxacin prophylaxis from developing countries. MATERIALS AND METHODS: We performed a retrospective study to explore the incidence, pattern, and clinical outcome of infections following AHCT in MM patients from 2010 to 2019 at our center. Patient-specific, disease-specific, and transplant-specific details were retrieved from the case files. The characteristics of infectious complications (site, intensity, organism, treatment, and outcomes) were analyzed. All patients who underwent transplantation from 2010 to 2016 received levofloxacin antibiotic prophylaxis. Common terminology criteria for adverse events (CTCAE) criteria (v5.0) were used for the grading of infections and regimen-related toxicity. International Myeloma Working Group updated criteria were used for the assessment of disease response before transplant and at day +100. RESULTS: Ninety-five consecutive patients with newly diagnosed multiple myeloma (NDMM) (n = 85), RRMM (n = 7), plasma cell leukemia (n = 2), and Polyneuropathy, Orgaomegaly, Endocrinopathy, Monoclonal gammopathy, skin abnormalities (POEMS) syndrome (n = 1) underwent AHCT during the study period. Their median age was 55 years (range 33-68); 55.8% were males. Immunoglobulin IgG kappa was the most common monoclonal protein (32.6%), International Staging System stage III disease was present in 45.3%, and 84.2% of patients achieved more than very good partial response before AHCT. The median time from diagnosis to AHCT was 10 months (range 4-144). Eighty-nine patients (93.7%) developed fever after AHCT. Fever of unknown focus, microbiologically confirmed infections, and clinically suspected infections were found in 50.5%, 37.9%, and 5.3% of patients, respectively. Clostridiodes difficile-associated diarrhea was observed in eight patients (8.4%). Neutrophil and platelet engraftment occurred after a median of 11 days (range 9-14) and 12 days (range 9-23), respectively. The median duration of hospital stay was 16 days (range 9-29). Only two patients (2.1%) required readmission for infections within 100 days of AHCT. Transplant-related mortality (TRM) in the study population was 4.2% (n = 4). The levofloxacin prophylaxis group (n = 32, 33.7%) had earlier neutrophil engraftment (day +10 vs. day +11) and platelet engraftment (day +11 vs. day +12), but time to fever onset, duration of fever, hospital stay, TRM, and day +100 readmission rates were not significantly different from those of patients without levofloxacin prophylaxis. There was no significant difference in the spectrum of infections between patients with and without levofloxacin prophylaxis. The overall survival and progression-free survival of the study population at 5 years were 72.7% and 64.8%, respectively. CONCLUSION: This study shows that the incidence of infections and TRM are higher in MM patients from lower-middle income countries after AHCT than in those from developed countries. The majority of such patients lack clinical localization and microbiological proof of infection. There was no significant difference in the spectrum of infections and their outcomes in patients with and without levofloxacin prophylaxis.

Management of thromboembolic disorders during pregnancy in resource-constrained settings: An Indian perspective.

Venous thromboembolism (VTE) in pregnancy and resulting thrombotic disorders are increasingly being recognized as an important cause of maternal morbidity and mortality. The diagnosis of VTE during pregnancy has an impact on current as well as future foeto-maternal outcomes. Whereas algorithms to manage VTEs during pregnancy in developed countries exist, these are difficult to implement in resource-constraint settings. In this narrative review, we discuss strategies that can be applied in daily clinical practice by obstetricians and haematologists dealing with these disorders in the country.

Feasibility of treatment-free remission with generic imatinib: Results of generic imatinib-free trial-in-chronic myeloid leukaemia-chronic phase study.

Background & objectives: Both innovator and generic imatinib are approved for the treatment of Chronic Myeloid Leukaemia-Chronic phase (CML-CP). Currently, there are no studies on the feasibility of treatment-free remission (TFR) with generic imatinib. This study attempted to determine the feasibility and efficacy of TFR in patients on generic Imatinib. Methods: In this single-centre prospective Generic Imatinib-Free Trial-in-CML-CP study, twenty six patients on generic imatinib for ≥3 yr and in sustained deep molecular response (BCR ABLIS ≤0.01% for more than two years) were included. After treatment discontinuation, patients were monitored with complete blood count and BCR ABLIS by real-time quantitative PCR monthly for one year and three monthly thereafter. Generic imatinib was restarted at single documented loss of major molecular response (BCR ABLIS>0.1%). Results: At a median follow up of 33 months (interquartile range 18.7-35), 42.3 per cent patients (n=11) continued to be in TFR. Estimated TFR at one year was 44 per cent. All patients restarted on generic imatinib regained major molecular response. On multivariate analysis, attainment of molecularly undetectable leukaemia (>MR5) prior to TFR was predictive of TFR [P=0.022, HR 0.284 (0.096-0.837)]. Interpretation & conclusions: The study adds to the growing literature that generic imatinib is effective and can be safely discontinued in CML-CP patients who are in deep molecular remission.

No role of common NOD2 gene variants in predicting sepsis related outcomes in Indian patients undergoing hematopoietic stem cell transplant.

Background: High-risk single nucleotide polymorphisms (SNPs) in nucleotide-binding oligomerization domain-2 (NOD2) gene are associated with high susceptibility for infections and inflammation due to risk of inappropriate cytokine production and NF-κB activation. We studied the incidence of three high-risk NOD2 gene SNPs (8, 12 and 13) among BM-transplant (BMT) recipients. Methods: Sequential patients undergoing BMT over 1-year period were prospectively studied. Patients were tested with MspI/HhaI or NlaIV restriction-endonucleases (Euryx, Gdansk, Poland) for NOD2 gene SNPs 8, 12, and 13, respectively. Regimen-related organ toxicity was graded using the Seattle-Bearman criteria. Results: Forty patients were enrolled, their median age was 38 years (range 3-64), and 52.5% were males. Twenty patients each (50%) underwent autologous and allogeneic BMT. Majority of the patients (n = 38, 95%) developed febrile-neutropenia in the post-transplant period and 4 patients died due to overwhelming sepsis within day +100. Acute graft-versus-host disease (GVHD) [grade I-II (n = 3) and grade III-IV (n = 6)] was observed in 9/20 allogeneic HSCT recipients. None of our 40 patients showed presence of any of the three NOD2 gene SNPs. Conclusion: The 3 commonly observed high risk SNPs (8,12, and 13) of NOD2 genes were not present in study population. It is quite likely that due to geographical and racial variations these polymorphisms are completely absent in North India. NOD2 gene is highly diverse and polymorphic variants can be absolutely different in various populations. Larger studies targeting sequencing of the whole NOD2 gene can convincingly rule out or confirm the role of NOD2 gene variants in Indian population.

Role of pre-transplant chest high-resolution computed tomography and serum galactomannan index in predicting post-transplant invasive pulmonary aspergillosis in allogeneic hematopoietic cell transplant recipients.

INTRODUCTION: The role of pre-HCT chest high-resolution computed tomography (HRCT) and serum galactomannan index (GMI) in predicting the post-allogeneic hematopoietic cell transplant (HCT) invasive pulmonary aspergillosis (IPA) is debatable. METHODS: This was a single-center, prospective study from 2014 to 2019. The primary objective was to study if pre-HCT chest HRCT and serum GMI predicted IPA post-HCT. The secondary objective was day +100 mortality. All consecutive, consenting patients of ≥12 years of age undergoing allo-HCT were included and had pre-HCT chest HRCT and serum GMI. All patients received mold active antifungal prophylaxis. The EORTC/MSG criteria were used for the diagnosis of IPA. RESULTS: A total of 82 patients with median age 27 years (12-59 years) were included. The underlying diagnoses included hematological malignancies (79%) and aplastic anemia (21%). Fifteen percent of patients was treated for prior history of probable IPA (>6 weeks before HCT). Pre-HCT chest HRCT satisfied EORTC clinical criteria in 24% patients. Serum GMI ≥0.5 was seen in 27% of patients. Post-HCT probable IPA was seen in 24% of patients. There were more patients with pre-HCT chest HRCT findings satisfying EORTC clinical criteria (45% vs. 18%, P = .014) and GMI ≥0.5 (45% vs. 21%, P = .03) in the group with post-HCT IPA compared to those without IPA. There was higher day+100 mortality in patients with post-HCT IPA (55% vs. 18%, P = .001). CONCLUSIONS: The presence of EORTC clinical criteria on pre-HCT chest HRCT, serum GMI ≥0.5, and prior history of IPA predicted post-HCT IPA.

Ultralow Lattice Thermal Conductivity at Room Temperature in Cu4 TiSe4.

Ultralow thermal conductivity draws great attention in a variety of fields of applications such as thermoelectrics and thermal barrier coatings. Herein, the crystal structure and transport properties of Cu4 TiSe4 are reported. Cu4 TiSe4 is a unique example of a non-toxic and low-cost material that exhibits a lattice ultra-low thermal conductivity of 0.19 Wm-1 K-1 at room temperature. The main contribution to the unusually low thermal conductivity is connected with the atomic lattice and its dynamics. This ultralow value of lattice thermal conductivity (kL ) can be attributed to the presence of the localized modes of Cu, which partially hybridize with the Se atoms, which in turn leads to avoidance of crossing of acoustic phonon modes that reach the zone boundary with a reduced frequency. Like a phonon glass electron crystal, Cu4 TiSe4 could also open a route to efficient thermoelectric materials, even, with chalcogenides of relatively high electrical resistivity and a large band gap, provided that their structures offer a sublattice with lightly bound cations.

Randomized controlled trial of twice-daily versus alternate-day oral iron therapy in the treatment of iron-deficiency anemia.

Recent studies in iron-depleted women have challenged the current approach of treating iron-deficiency anemia (IDA) with oral iron in divided daily doses. Alternate day dosing leads to more fractional absorption of iron. In this randomized controlled trial, we looked at the efficacy and safety of alternate-day (AD) versus twice-daily (BD) oral iron in all severity of IDA. Total of 62 patients were randomized, 31 patients in BD arm received 60 mg elemental iron twice daily while 31 patients in AD arm received 120 mg iron on alternate days. The primary endpoint of 2 g/dl rise in hemoglobin was met in significantly more patients in the BD arm at 3 weeks (32.3% vs. 6.5%, p < 0.0001) and 6 weeks (58% vs. 35.5%, p = 0.001). There was a significant rise in the median hemoglobin at 3 (1.6 vs. 1.1, p = 0.02) and 6 weeks (2.9 vs. 2.0 g/dl, p = 0.03) in the BD arm. However, the median hemoglobin rise in the AD arm at 6 weeks was not significantly different than the BD arm at 3 weeks. Alternate-day dosing for 6 weeks and twice-daily dosing for 3 weeks resulted in the provision of the same total amount of iron. There were more reports of nausea in the BD arm (p = 0.03). In conclusion, the choice of twice-daily or alternate-day oral iron therapy should depend on the severity of anemia, the rapidity of response desired, and patient preference to either regimen due to adverse events. Trial Registration: CTRI reg. no. CTRI/2018/07/015106 http://ctri.nic.in/Clinicaltrials/login.php.

Quality of life in patients of chronic lymphocytic leukemia using the EORTC QLQ-C30 and QLQ-CLL17 questionnaire.

INTRODUCTION: The quality of life (QoL) analysis is likely to differ by region, ethnicity, and questionnaires in comparison with age-matched healthy controls. METHODS: The EORTC QLQ-C30 and QLQ-CLL17 questionnaire validated in regional languages were administered to 127 consecutive CLL and 100 age-matched, healthy controls at a single center from 2018 to 2019. RESULTS: All groups of CLL patients either on wait and watch (W&W) or on treatment had significantly impaired QoL in all functional domains including global health compared to controls (P < .0001). CLL patients had significantly higher symptom scores than controls in most domains (P < .0001, 0.03 for diarrhea). There was no difference in the QoL by age or gender. Lower socioeconomic status patients had higher financial difficulty (P = .02). Patients on CIT had the worst global health (OR 12.21 compared to patients on W&W) (P = .03). Patients on ibrutinib had less worries/fears about health and functioning than patients who were on CIT (P = .04). CONCLUSIONS: Quality of life is severely affected in CLL patients on W&W. Global health status and worries about future health and functioning were major concerns. Socioeconomic status but not age or gender impacted QoL. Patients on ibrutinib had better QoL than on CIT.

Resolution of high output pulmonary edema due to hyperviscosity with plasma exchange in a patient with multiple myeloma- a case report.

Symptomatic hyperviscosity is an oncologic emergency which is suspected when patients with certain hematogical malignancies present with neurological symptoms. Hyperviscosity syndrome is a rare clinical manifestation in multiple myeloma. We describe a case of a 61 year old lady who developed pulmonary infiltrates after being diagnosed with multiple myeloma. Treated as an infection with antibiotics and intravenous immunoglobulin, she had neurological symptoms which suggested the possibility of hyperviscosity syndrome. The patient received one session of plasma exchange with which her symptoms improved and chest infiltrates resolved (high output pulmonary edema). The case highlights a known but rare manifestation of multiple myeloma, which when diagnosed and treated quickly can have gratifying results.

Efficacy of therapeutic plasma exchange in a patient with coagulation inhibitors (acquired haemophilia A) - A case report.

Acquired haemophilia A (AHA) is a rare disorder with mostly idiopathic aetiology that leads to factor VIII (FVIII) deficiency due to coagulation inhibitors formation. Treatment protocol includes immunosuppression and Factor VIII bypassing agents including activated Prothrombin Complex Concentrates (PCC). Nevertheless, the role of plasma exchange is not clear in the treatment of AHA. We report a case of 73 year old male who presented with haematuria, prolonged activated partial thromboplastin time (APTT) and a very high titres of Factor VIII inhibitors of 98 Bethesda units (BU) and was diagnosed with acquired haemophilia A. He failed to respond to multiple immunosuppressive therapies including rituximab. Therefore, therapeutic plasma exchange (TPE) therapy was planned due to persistence of haematuria despite immunosuppressive therapies. After five cycles of plasma exchange, APTT became normal, haematuria subsided and Factor VIII inhibitors became negative. Patient was discharged without any bleeding and in a stable condition. In this index case, plasma exchange played a very crucial role, resulting in recovery of the patient. These results advocate that therapeutic plasma exchange is an effective therapy for acquired haemophilia A.

A Curious Case of "Septic Shock".

BACKGROUND: Takayasu arteritis, also known as "pulseless disease," causes proximal occlusion of the lumen of large arteries of the neck and arm, leading to impalpable pulses and "pseudohypotension." This may misdirect the management plan for a patient in the emergency setting if the presence of vascular occlusion is not previously known. CASE REPORT: We describe a young woman who presented to the emergency department (ED) with fever. On evaluation, she had shock, which was not responsive to a fluid bolus. Bedside Rapid Diagnostic Test was positive for Plasmodium vivax, and a diagnosis of severe vivax malaria was made. She was started on intravenous artesunate and vasopressors in view of her persistent hypotension in the face of a normal central venous pressure. A thorough examination at that time revealed palpable lower limb pulses with feeble upper limb pulses. Vasopressors were tapered while monitoring lower limb blood pressure. Computed tomographic angiogram confirmed the diagnosis of Takayasu arteritis. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Hypotension and shock are regularly encountered in the ED. Occlusive arterial disease involving upper limbs can mimic refractory shock, leading to potentially harmful and unnecessary interventions. Emergency physicians should be aware of this possibility. A simple routine of quickly checking all peripheral pulses would help them avoid this pitfall.

Superolateral dislocation of an intact mandibular condyle into the temporal fossa: case report and literature review.

Temporomandibular joint dislocation refers to the dislodgement of mandibular condyle from the glenoid fossa. Anterior and anteromedial dislocations of the mandibular condyle are frequently reported in the literature, but superolateral dislocation is a rare presentation. This report outlines a case of superolateral dislocation of an intact mandibular condyle that occurred in conjunction with an ipsilateral mandibular parasymphysis fracture. A review of the clinical features of superolateral dislocation of the mandibular condyle and the possible techniques of its reduction ranging from the most conservative means to extensive surgical interventions is presented.

Amino Acid Chirality and Ferrocene Conformation Guided Self-Assembly and Gelation of Ferrocene-Peptide Conjugates.

The self-assembly and gelation behavior of a series of mono- and disubstituted ferrocene (Fc)-peptide conjugates as a function of ferrocene conformation and amino acid chirality are described. The results reveal that ferrocene-peptide conjugates self-assemble into organogels by controlling the conformation of the central ferrocene core, through inter- versus intramolecular hydrogen bonding in the attached peptide chain(s). The chirality controlled assembling studies showed that two monosubstituted Fc conjugates FcCO-LFLFLA-OMe and FcCO-LFLFDA-OMe form gels with nanofibrillar network structures, whereas the other two diastereomers FcCO-DFLFLA-OMe and FcCO-LFDFLA-OMe exclusively produced straight nanorods and non-interconnected small fibers, respectively. This suggests the potential tuning of gelation behavior and nanoscale morphology by altering the chirality of constituted amino acids. The current study confirms the profound effect of diastereomerism and no influence of enantiomers on gelation. Correspondingly, the diastereomeric and enantiomeric Fc[CO-FFA-OMe]2 were constructed for the study of chirality-organized structures.

Coexistence of BCR∷ABL1 translocation and JAK2V617F mutations in indian patients with myeloproliferative neoplasms: A case series.

ABSTRACT: BCR∷ABL1 translocation and JAK2V617F mutations are canonical variants of myeloproliferative neoplasms (MPNs). Traditionally considered mutually exclusive, they may rarely coexist. We report the clinicopathological profile and treatment outcomes of four MPN patients with coexistence of these disease-defining genetic variants. Both mutations were detected simultaneously in three patients who did not harbor tell-tale signs of CML and were evaluated for both BCR∷ABL1 and JAK2V617F based on clues from hemogram, peripheral-blood and bone-marrow examination. All were treated with imatinib and hydroxyurea and attained major molecular response after 2-7 months. In another patient, JAK2V617F was detected 15 years after the diagnosis of CML at the time of evaluation of loss of hematological and molecular response. She was treated with dasatinib but no hematologic or molecular response was attained after 6 months despite good compliance. In conclusion, BCR∷ABL1 and JAK2V617F may rarely coexist in MPN with variable temporal evolution, clinicopathological profile, and treatment response.

Challenges in Administering Salvage Therapy and Outcomes of Relapsed/Refractory Diffuse Large B-Cell Lymphoma Patients: A LMIC Real-World Study.

Standard therapy for patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma (RR DLBCL) involves salvage chemotherapy followed by autologous hematopoietic stem cell transplant. However, information regarding the number of patients receiving salvage therapy and associated factors is not available from low/middle income countries (LMICs). All patients treated at our center with RR DLBCL from 2016 to 2021 were included in the study. Univariate and multivariate analyses was performed to find factors associated with the lack of receipt of salvage chemotherapy. Eighty-five patients were included in the study. Most patients had primary refractory disease (69.4%). Only 26 patients received standard salvage therapy, while the others (N = 59) received metronomic/palliative oral therapy. On univariate analysis, patients with an annual income below India's Gross National Income per capita (p = 0.014), an education level below Class XII (p = 0.025), Stage III/IV disease at relapse (p = 0.018) and CNS relapse (p = 0.027) were more likely to receive palliative therapy. Conversely, patients with a late relapse were more likely to receive salvage therapy (p = 0.001). On multivariate analysis, patients with Stage III/IV relapse (p = 0.030) and an education level less than Class XII (p = 0.012) were more likely to receive palliative therapy, while patients with a late relapse (p = 0.001) were more likely to receive salvage therapy. Patients who received salvage therapy had a longer Median OS than those who received palliative therapy (p < 0.001). Timing of relapse, stage at relapse and educational status of the patient are significant factors affecting access to effective therapy for patients with RR DLBCL in LMICs.

Comparable outcomes with low-dose and standard-dose horse anti-thymocyte globulin in the treatment of severe aplastic anemia.

BACKGROUND: The standard dose (SD) of horse anti-thymocyte globulin (hATG) ATGAM (Pfizer, USA) or its biosimilar thymogam (Bharat Serum, India) for the treatment of Aplastic Anemia (AA) is 40 mg/kg/day for 4 days in combination with cyclosporine. Data on the impact of hATG dose on long-term outcomes are limited. Here, we describe our comparative experience using 25 mg/kg/day (low-dose [LD]) hATG for 4 days with SD for the treatment of AA. METHODS: We retrospectively studied patients with AA (age > 12 years) who received two doses of hATG combined with cyclosporine. Among 93 AA patients who received hATG, 62 (66.7%) and 31 (33.3%) patients received LD and SD hATG with cyclosporine, respectively. Among these,seventeen(18.2%) patients also received eltrombopag with hATG and cyclosporine. Overall response rates [complete response (CR) and partial response (PR)] of LD and SD hATG groups at 3 months (50% vs. 48.4%; p = 0.88), 6 months (63.8% vs. 71.4%; p = 0.67), and 12 months (69.6% vs. 79.2%; p = 0.167) were comparable. The mean (Standard Deviation) 5-year Kaplan-Meier estimate of overall survival and event-free survival was 82.1 (4.6)% and 70.9 (5.5)% for the study population. The mean (standard deviation) 5-year Kaplan-Meier estimate of overall survival and event-free survival of those who received LD hATG versus SD hATG dose was 82.9 (5·3)% versus 74.8 (10·3)% (P = 0·439), and 75.2 (6.2)% versus 61.4(11.2)% (P = 0·441). CONCLUSION: Our study revealed that the response rates of patients with AA and LD were similar to those of patients with SD to hATG combined with cyclosporine in a real-world setting.