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PURPOSE The outcomes of patients with myeloma from developing countries are often lacking because of poor record maintenance. Publications from such settings are also limited because of the retrospective nature of the data collection. Information technology can bridge these gaps in developing countries with real-time data maintenance. We present the real-time survival data of the patients with myeloma from a tertiary care center in North India using one such indigenously built software. PATIENTS AND METHODS These are real-time data of all patients with myeloma presenting to a tertiary care center from North India. The patient characteristics (demographics, baseline disease characteristics, risk stratification, and outcomes) were recorded contemporaneously. The survival of the study population was analyzed and grouped based on various disease characteristics at diagnosis. RESULTS The median age of the study population (N = 696) was 65.9 (34.9-94.9) years with male predominance (65%). The median follow-up was 3.7 years (0-18.6 years) with the median overall survival (OS) not achieved. The OS of the study population at 1, 3, and 5 years was 94% (n = 558), 87.5% (n = 394), and 83.1% (n = 267), respectively. Most of the patients presented in advanced stages based on International Staging System (III:70%). On Kaplan-Meier analysis, the presence of weight loss ( P = .01), renal dysfunction ( P = .047), and anemia at diagnosis ( P = .004) had a significant impact on survival. On Cox proportional model univariate analysis, the presence of renal dysfunction, anemia, and weight loss had the significant hazard ratio of 1.68 (1-2.82, P = .049), 3.18 (1.39-7.29, P = .0063), and 2.81 (1.22-6.42, P = .014), respectively, whereas on multivariate analysis of hypercalcemia, renal disease, anemia, and bone disease (CRAB) features, only anemia was found to have a significant hazard ratio of 2.56 (1.01-6.47, P = .046). CONCLUSION The real-world data show OS comparable with the published western literature. Only anemia was found to have significant impact on survival. The use of such software can aid in better data-keeping in resource-constrained settings.

Uday, Yanamandra, Revanth Boddu, Suman Pramanik, Kundan Mishra, Rajan Kapoor, Ankur Ahuja, Tathagata Chatterjee, and Satyaranjan Das. Prevalence and clinical characteristics of post-thrombotic syndrome in high-altitude-induced deep vein thrombosis: experience of a single tertiary care center from real-world settings.

Background: Down Syndrome (DS) children with acute myeloid leukemia (AML) have unique differences in clinical features, epidemiologic nature, and biologic patterns of disease compared with AML in children without DS. Aims and Objective: AML in DS children should be considered distinct disorder from AML in Non DS population and treatment needs to be customized for this population. In this retrospective study spanning from 2014 to 2019 we present our experience of managing leukemia in children with DS. Materials and Methods: From 2014 and 2019, 72 children aged below 18 years were managed at our institute with acute myeloid leukemia (AML). Out of these 72 children with AML, 7 children were with DS which was confirmed by karyotyping. Majority of these children had M7 while M2 and M4 subtypes were seen in one child each. On conventional karyotyping in addition to trisomy 21 additional cytogenetic abnormalities were seen in 4 patients. Two children had trisomy 8. One child had deletion of 11 chromosomes and one had translocation between 8 and 21 chromosomes. Results: All 7 children were administered intensive chemotherapy with curative intent after informed parental consent. All 7 children achieved complete remission. Four out of 7 children had complications related to severe neutropenia. Conclusion: All patients of DS with AML should be offered chemotherapy with curative intent. Endeavour should be to give less aggressive chemotherapy protocol to bring down treatment related mortality.

There are no definitive guidelines for management of chronic or refractory immune thrombocytopenia (ITP) in children. Dapsone is an inexpensive and efficacious, yet neglected, therapeutic option for treatment of chronic ITP. We evaluated the efficacy and safety of dapsone in the management of chronic ITP in children. Children with chronic ITP

Introduction: This study was conducted to find if cord blood lactate correlates well with Apgar score and umbilical cord blood pH and subsequent development of hypoxic ischemic encephalopathy (HIE). Materials and Methods: It was a cross sectional, observational study which was conducted at a tertiary care referral center of North India from June 2018 to June 2019. Monitoring of cord blood lactate levels along with Apgar and cord blood pH was done for correlation of cord blood lactate with Apgar, cord blood pH, and subsequently development of HIE. Results: During the study period, 115 term neonates got enrolled based on inclusion criteria. Out of these, 83 babies had some degree of HIE based on Sarnat staging. Among these 83 neonates with encephalopathy, 36 had Stage III HIE while, 28 and 19 babies had Stage II and Stage I encephalopathy, respectively. Lactate levels correlated negatively with Apgar score and umbilical cord blood pH and higher levels of lactate correlated well with lower Apgar and cord blood pH. The mean lactate level was significantly higher in cases with HIE (5.18 mmol/L) as compared to cases without HIE (2.91 mmol/L). Conclusion: Our study shows that cord blood lactate can be used as a predictor for perinatal hypoxia. With the availability of cheaper handheld lactate monitors, lactate monitoring may become more practical option and need to be explored.

Background: Immune thrombocytopenia (ITP) is a benign hematological disorder characterized by low platelet counts in peripheral blood and spectrum of various bleeding manifestations. Azathioprine is one of the effective, readily available, and affordable immunosupressants available for ITP management in developing countries. We aimed to study the efficacy and long-term safety profile of our patients with ITP who were treated with azathioprine. Method: This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India. The patients who had received at least one line of therapy before receiving azathioprine were included in this study. All patients received oral azathioprine at a dose of 1 mg/kg/day (50 mg or 100 mg tablet formulations were used), which was increased up to 2 mg/kg/day depending upon the response and adverse effects. Result: Sixty-three patients were analyzed. Their median age was 28 years (range 15-68); 29/63 patients (46.03%) were females. The median duration from diagnosis to azathioprine initiation was 539 days (323 days-980.5 days). The patients included in the study had received a median of 3 (range 1-6) prior lines of therapies; 38/63 patients (60.32%) had received ≥3 prior therapies. Six patients (9.5%) had relapsed after splenectomy, and 16 patients (25.4%) had relapsed after receiving rituximab. The mean baseline platelet count was 10000/μL. The median time to response was 95 days (90 days-not reached) and the cumulative overall response rate (complete and partial response) at day 90 was 38.1%. Only one patient achieved complete response with azathioprine in our study. The cumulative rate of relapse at five years was 21.2%. Twenty-six patients stopped azathioprine after achieving some response (CR/PR) with Azathioprine for a median duration of 1067.5 days (range: 236 days-2465 days). They were followed up for a median of 870 days (range: 392 days-1928 days), and twelve of them relapsed. Twenty-six patients (26/63, 41.27%) reported one or more adverse events while on azathioprine. Leucopenia was the most frequent adverse event, followed by anemia and hepatobiliary laboratory abnormalities. Serious adverse events (grade ≥3 CTCAEv4) were noted in three patients (4.7%). One patient succumbed to severe sepsis multiorgan dysfunction while being on treatment. Conclusion: We conclude that azathioprine has a good response rate in chronic ITP patients. It is well-tolerated with minimal and manageable side effects.

Immune thrombocytopenia (ITP) is characterized by decreased platelet count in the peripheral circulation. The first-line therapy is corticosteroids with 53-80% overall response rate. Eltrombopag has been used as second-line therapy in ITP for over a decade now. The long-term efficacy and safety profile have been widely reported in the western world. However, the data from the resource-constraint settings of the developing world is scarce. We aim to present the real-life experience of efficacy and safety of eltrombopag from the resource-constraint settings. This was a retrospective, single-center study conducted at a tertiary care hospital in Northern India from 2012-2019. On audit of medical records, patients of ITP receiving eltrombopag were screened for inclusion. Patients whose treatment outcomes were not available were excluded. Finally, 53 patients were analyzed using statistical packages of Python v3.7. The patients’ median age was 35 years (range 17-78), with 23 (43.4%) being female. The median time to response was 35 days (range 28-50 days) and the cumulative overall response rates (ORR) at day 30, day 60 and day 90 were 41.5%, 69.8%, and 81.1% respectively. A total of 10 patients on eltrombopag relapsed during follow up. The cumulative rate of relapse at one year, three years, and five years were 6.6%, 25.3%, and 47.7%, respectively. There was no significant difference in outcome (response rate or relapse) in any subgroups depending on age, sex, duration of disease, number of prior lines of treatment, splenectomy, or baseline platelet count. Six patients stopped eltrombopag after having a median sustained response for 796 days (range 658-1185), and after a median follow up of 624 days (range 92-1339), they continued to be in remission. Seventeen patients (17/53, 32%) reported one or more adverse events while on eltrombopag therapy. A total of 49 adverse events (n=4, grade ≥3 CTCAEv4) were noted. Anemia was the most frequent adverse event followed by hepatobiliary dysfunction as reflected by deranged AST/ALT or raised bilirubin. The use of eltrombopag among adult ITP patients in resource-constraint settings was well-tolerated and yielded excellent overall response. The benefit was found to be sustained on long-term follow up. However, events like anemia, hepatobiliary, and thrombotic complications merit closer follow up.

Lactic acidosis (LA) is characterised by persistently increased blood lactate >5 mmol/L. Type A LA due to anaerobic glycolysis is frequently seen during management of haematological malignancies. A rare form of LA known as type B LA, which occurs as a result of metabolic dysregulation at cellular level has been described recently. This has been reported to be because of Warburg effect (WE) or aerobic glycolysis, which is seen in cancerous cells as they rely on aerobic glycolysis rather than oxidative phosphorylation for energy generation. Presence of type B LA at initial presentation of haematological malignancies is a poor prognosticating factor and has rarely been reported in children. We present a child with T cell acute lymphoblastic leukaemia with mild phenotype of type B LA due to WE. She responded dramatically to definitive chemotherapy and tolerated intensive phase of chemotherapy without any significant morbidity.

Background The standard practice during high-dose methotrexate (HD-MTX) in acute lymphoblastic leukemia (ALL) to mitigate toxicity is to serially monitor levels till serum MTX Procedure This prospective observational study consecutively enrolled children with ALL receiving HD-MTX. Cycles with unavailable MTX36 and MTX36 > 10 μmol/L were excluded. HD-MTX was administered over 24 hours (BFM-2009 protocol) with 12 hours of prehydration. MTX36 were performed at other centers. Leucovorin was given in six hourly doses 36 hours post HD-MTX. Hydration was continued until the last dose of leucovorin. MTX toxicities, including change of creatinine from baseline at 36 hours (∆Cr36 ), were noted. Two groups depending on MTX36 (≤1 μmol/L vs > 1 μmol/L) received six versus eight doses of leucovorin, and toxicities were compared. Results Twenty-nine children with median age five years (1-11) who received 100 HD-MTX cycles with a median MTX dose of 3 g/m2 (2-5) were analyzed. The median MTX36 level was 1.165 μmol/L (0.1-7.32). Toxicities of HD-MTX (CTCAE-4.0): transaminitis-22%; creatinine elevation ≥ 1.25 times baseline-24%; cytopenias-16%; mucositis-17%; acute kidney injury (AKI)-6%. All toxicities were ≤CTCAE grade 3. Creatinine elevation, AKI, and mucositis were significantly higher in the group with higher MTX36 . There was no correlation (r = 0.3) between ∆Cr36 and MTX36 . MTX36 was thrice more economical than the standard protocol. Conclusion MTX36 is a potential cost-effective, efficacious, and safe limited sample strategy to monitor HD-MTX, particularly in centers where in-house MTX levels are unavailable.

Salt-free stereoselective synthesis of silyl enol ethers was achieved by treating α-halo carbonyl compounds with 2,3,5,6-tetramethyl-1,4-bis(trimethylsilyl)-1,4-dihydropyrazine. In this reaction, easily removable trimethylsilyl halides and 2,3,5,6-tetramethylpyrazine were generated as the reaction byproducts. Due to the inertness of the reaction byproducts, we found a one-pot transformation of the in situ generated silyl enol ethers into various α-functionalized carbonyls by reaction with Togni-II reagent or aldehydes.

Pyridine- and quinoline-stabilized silyl cations have been prepared, and their structure in condensed phases unambiguously assigned using 1H, 13C, 15N, 29Si, and 1H DOSY NMR as well as X-ray diffra...

Lead, an ubiquitous toxicant emitted from environmental and industrial sources, causes multiple adverse effects following acute or chronic exposure. Sometimes the sources of heavy metal exposure are unanticipated. We report a case of acute lead poisoning presenting with adverse haematological

International audience; Pd-nanoparticles catalyzed dehydrogenative coupling between various hydrosilanes and alcohols was shown to provide silyl ethers in good and reproducible yields. The synthetic methodology is effective for a wide range of simple and bulky silanes and secondary alcohols, while keeping various other functional groups intact. The procedure also exhibits high selectivity for the silylation of primary versus secondary alcohols in 1,2-diols, and allows the successive silylation of alkynols and hydrogenation of the triple bond to afford Z-alkenols in good yields.

An unprecedented intramolecular rearrangement of α-azidoperoxides, promoted by simple organic base to provide tert-butyl esters, has been presented. Further, a one-pot methodology consisting of in situ generation of the α-azidoperoxides from corresponding aldehydes followed by base-promoted rearrangement to obtain the desired ester has also been executed. Relevant mechanistic studies, to provide the proof for intramolecular alkoxy transfer, are investigated.

We report a transition metal-free dehalogenation of vicinal dihalo compounds by 1,1′-bis(trimethylsilyl)-1H,1′H-4,4′-bipyridinylidene (1) under mild conditions, in which trimethylsilyl halide and 4,4′-bipyridine were generated as byproducts. The synthetic protocol for this dehalogenation reaction was effective for a wide scope of dibromo compounds as substrates while keeping the various functional groups intact. Furthermore, the reduction of vicinal dichloro alkanes and vicinal dibromo alkenes also proceeded in a salt-free manner to afford the corresponding alkenes and alkynes.

Transcobalamin (TC) deficiency is a rare autosomal recessive inborn error of cobalamin transport which clinically manifests in early infancy. We describe a child with TC deficiency who presented with classical clinical and lab stigmata of inborn error of vitamin B12 metabolism except normal serum B12 levels. He was started on empirical parenteral cobalamin supplements at 2 months of age; however, the definitive diagnosis could only be established at 6 years of age when a genetic evaluation revealed homozygous nonsense variation in exon 8 of the TCN2 gene (chr22:g.31019043C>T).

An unprecedented synthesis of α-azido-peroxides has been developed using an FeCl3-catalyst starting from carbonyl, TMS-azide, and hydroperoxide. Further, a base promoted decomposition of synthesized secondary α-azido-peroxides to provide the corresponding tert-butyl esters has been disclosed. Finally, an asymmetric kinetic resolution of such α-azido-peroxides has also been developed to provide chiral α-azido-peroxides in excellent enantiopurity.

The etiology of ITP remains unknown but its pathogenesis consists of loss of tolerance to platelet antigens. There is a complex dysregulation of the immune system involving both the B cells and the T cells. Splenectomy is the standard second line option in steroid refractory chronic ITP patients. However, costs of surgery and reluctance for surgery in severely thrombocytopenic patients on part of surgeons are major obstacles in resource limited settings. Rituximab has been used in both the standard doses of 375 mg/m2 and low doses of 100 mg/m2 with similar results. We studied the utility of low dose Rituximab (@100 mg/m2 weekly × 4 doses) in resource limited settings. Overall response, complete response (CR) and partial response (PR) rates were 47.6% (10/21), 33.3% (7/21) and 14.3% (3/21) respectively. Median time to response in patients achieving CR was 75 days (range 45–185 days) while in patients achieving PR it was 105 days (range 45–165 days). However, there was no significant difference between males and females achieving CR or PR. We also observed that patients who had earlier responded to any form of treatment were more likely to respond to Rituximab treatment. The cumulative relapse free survival (RFS) at 13 months was 78%. By giving lower dose, six times less than conventional dosing dose, we have been able to demonstrate cost effectiveness in our study population. We were able to administer all the doses in day care without any major adverse events leading to further cost savings on in-patient care.

An enantioselective intramolecular oxa-Michael reaction of enols catalyzed by a squaramide-containing tertiary amine based bifunctional organocatalyst, which efficiently activates the o-homoformyl chalcones, provides chiral isochromenes in moderate yields and good to excellent enantioselectivities.

An unprecedented enantioselective intramolecular oxa-Michael reaction of enols has been described. A squaramide-containing tertiary amine based bifunctional organocatalyst efficiently activates the o-homoformyl chalcones to provide the chiral isochromenes in moderate yields and good to excellent enantioselectivities. Further, late-stage functionalizations of the vinyl ether moiety of the chiral isochromene products have also been exemplified.

Introduction: The outcomes of Philadelphia positive acute lymphoblastic leukemia(Ph-ALL) have improved significantly after the introduction of tyrosine kinase inhibitors (TKI). The presence of Philadelphia positivity once considered as poor prognosis mandating transplantation, now even can be managed with TKI added to steroids. The data is scarce on Ph-ALL from real-world settings with resource constraints. Objective: To study the characteristics and outcomes of Ph+ve ALL from real world settings. Methodology: It is a retrospective observational study wherein the data of all patients of Ph-ALL managed at a tertiary care center in North India over the last 14 years (2004-2018) were analyzed. All case records of the Ph-ALL were perused, digitalized and their survival statistics derived. Results:Amongst a total of 611 ALL case records, 55 (9%) were Ph-ALL. Ph-ALL cases with complete data (n-51) were analysed for overall survival. The mean age of the patients was 31± 2.41 years (range 3-76) (Fig. 1A). Males constituted 74.5% (n-38) and females, 25.4% (n-13) of our cohort. On risk stratification, 11 (21.5%), 5 (9.8%), and 35 (68.6%) patients were classified as standard, intermediate and high risk. Twenty five percent patients had associated complex karyotype in addition to the Ph positivity. Of these 24 patients (47.05%) received adult ALL (GMALL protocol), 15 patients (29.4%) received paediatric BFM protocol, and12 patients (23.5%) received Hyper-CVAD. Week 4 Bone marrow evaluation was in CR in 87.2% of patients. L-Asparaginase was given in only 60% of the patients. An interruption in the therapy of more than 2 weeks for various reasons was present in 23.4% of the patients, mainly secondary to infections. Prophylactic cranial irradiation was given in 34.7% of the patients and high dose methotrexate was given in 30.4% of the patients. Relapse was seen in 22% of the patients. CNS disease was present in 17.6% of the patients. Only 19.6% of the patients were subjected to transplant. All patients received TKI, of which 44% received high dose imatinib and 56% patients received dasatinib. A total of 19.6% patients succumbed to the illness at various stages of the therapy. The cumulative overall survival at 1y (1y-OS) was 95.68% with 3y and 5y OS being 72.09% and 63.07% (Fig. 1B). The survival was not statistically different between patients with and without complex karyotype (p-0.52),based on type of TKI administered (Dasatinib Vs high dose Imatinib) (p-0.76), males and females (p-0.41), risk category (p-0.41) or by the presence of CNS disease (p-0.21) (Fig. 1C-G). The survivals based on the type of protocol was statistically different with the best survival with GMALL protocol and the least survival with Hyper-CVAD therapy (log rank p Conclusion: We have demonstrated in this study the improved outcomes of Ph-ALL who usually present late in resource constraint settings. There was no additional benefit of dasatinib over high dose imatinib in this cohort. Figure 1. Figure 1. Disclosures No relevant conflicts of interest to declare.

Introduction: The outcomes of Adolescent and young adult (AYA) have been studied in various hemato-oncology subsets. Patients of AYA-ALL have improved outcomes by paediatric-inspired or fully paediatric protocols. The outcomes published from trials are different from the actual practise, that too in the real-world settings with resource constraints. Objective: To study the characteristics and outcomes of AYA-ALL from real world settings. Methodology: It is a retrospective observational study wherein the data of all patients of AYA-ALL managed at a tertiary care center in North India over the last 14 years (2004-2018) were analyzed. All case records of the AYA-ALL were perused, digitalized and their survival statistics derived. Results:Amongst a total of 611ALL case records, 116 (18.98%) were AYA-ALL. AYA-ALL cases with complete data (n-116) were analysed for overall survival. The mean age of the patients was 26.65 ± 6.61 years (range 16-39) (Fig. A). Males constituted 32.7% (n-78) and females, 67.2% (n-38) of AYA-ALL. On risk stratification, 67 (57.7%), 26 (22.4%), and 23 (19.8%) patients were classified as standard, intermediate and high risk. Phenotypically, 78 patients were B-ALL, 23 were T-ALL and rest were MPAL. Of these 61 patients (52.5%) received adult ALL (GMALL protocol), 26 patients (22.3%) received paediatric BFM protocol, 19 patients (16.3%) received Hyper-CVAD, 8 patients (6.8%) MCP841 protocol and 2 received modified drugs not adhering to any fixed protocol. Week 4 Bone marrow evaluation was in CR in 91.4% of patients. L-Asparaginase was given in only 74.5% of the patients. An interruption in the therapy of more than 2 weeks for various reasons was present in 35% of the patients. Prophylactic cranial irradiation was given in 42.4% of the patients and high dose methotrexate was given in 25.2% of the patients. Relapse was seen in 27.7% of the patients. CNS disease was present in 9.4% of the patients. Only 8% of the patients were subjected to transplant. The cumulative overall survival at 1y (1y-OS) was 86.98% with 3y and 5y OS being 67.9% and 55.6% (Fig. B). The survivalsbased on the type of protocol was statistically different with the best survival with GMALL protocol and the least survival with Hyper-CVAD therapy (log rank p-0.0011) (Fig.C). The survival was also significantly different between different risk groups (p-0.003) (Fig.D). The survival was not statistically different between males and females (p-0.5), B-ALL vs T-ALL (p-0.6) (Fig. E, F). Conclusion: We have demonstrated in this study the improved outcomes of AYA-ALL who usually present in late chronic phase in resource constraint settings. Contrary to the belief, adult GMALL protocol had better survival vis-à-vis pediatric BFM protocol in this cohort of AYA-ALL. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

Using tBuOK in stoichiometric as well as catalytic amounts and with slight modifications (temperature, solvent), a variety of benzyl and cinnamyl azides can be transformed into the corresponding homoallylic amines.

The required alkyl or aryl α-azidoperoxide substrates may be prepared in situ starting from the corresponding aldehydes, thus offering a convenient one-pot two-step approach to tertiary alkylesters.

An efficient transition metal-free approach for the generation of N-unsubstituted imines from azides followed by trapping with allyl nucleophile to provide N-unsubstituted homoallylic amines has been described. Although catalytic KO(t)Bu in DMSO is sufficient to allow imine generation, stoichiometric KO(t)Bu is essential in THF. Further, an enantio- and diastereoselective synthesis of homoallylic amines from benzyl azide has also been exemplified.

Azidocarbenium ions, which are formed in the presence of a lewis acid from gem-diazides, have been trapped by nucleophiles for the first time.

For the first time, a sensitive azidocarbenium ion intermediate has been trapped with various nucleophiles to provide azides in excellent chemoselectivity. This provides a novel approach for the chemoselective synthesis of primary and secondary benzyl azides from aldehydes in a one-pot reaction. Enantioselective nucleophilic addition to the azidocarbenium ion has also been initiated.

An unprecedented synthesis of α-azido-peroxides has been developed using an FeCl3-catalyst starting from carbonyl, TMS-azide, and hydroperoxide. Further, a base promoted decomposition of synthesized secondary α-azido-peroxides to provide the corresponding tert-butyl esters has been disclosed. Finally, an asymmetric kinetic resolution of such α-azido-peroxides has also been developed to provide chiral α-azido-peroxides in excellent enantiopurity.

A mild, chemoselective, open-flask, and one-pot protocol for the synthesis of the title compounds (IV), (VI), (VIII), and (X) is presented.

A one-pot, three-component synthesis of homoallylic azides from corresponding aldehydes, TMS-allyl, and TMS-N3 has been developed for the first time using an FeCl3 catalyst. The aromatic and hetero-aromatic aldehydes provided the corresponding homoallylic azides with excellent chemoselectivity. This direct azido-allylation process is also readily scalable (1–28 mmol). The mechanism of the process is proposed. Finally, the selective as well as simultaneous functionalization of homoallylic azides has also been exemplified.

Three-component synthesis of protected secondary and "for the first time" tertiary homoallylic amines is achieved from carbonyl, carbamate, and allyltrimethylsilanes using a Re(2)O(7)-catalyst under mild and open flask conditions. Excellent chemoselectivities and diastereoselectivities were observed.