ALBERT

Description: Introduction: The haematological parameters, regulation of erythropoiesis, erythropoietin and body iron stores have been variably studied in dwellers and transient visitors from high altitude. Even in individuals born at high altitude, transient movements out of high altitude can significantly change these parameters. The role of this genetic adaption (reduced erythropoiesis) in Tibetans is well described (Moore LG et al, High Alt Med Biol 2001). There are scarce studies on true native highlanders and 'Ladakhi' populace from India which is geographically co-located to Tibet but of different ethnic origin (Wu TY et al, Zhongguo Ying Yong Sheng Li XueZaZhi. 2013). Objective: To study complete blood counts including red cell and platelet indices in native highlanders and influence of high altitude living on body iron stores and serum erythropoietin levels in true native highlanders. Methodology: True native highlanders in this study are defined as individuals born at altitudes above 11500ft with no descent to lower altitudes ever in their life. Baseline anthropometric data and peripheral oxygen saturations were collected. Haematological work up included total haemoglobin, haematocrit, total/ differential leucocyte count, platelets, red cell and platelet indices done by Sysmax® automated counter at Leh, Ladakh and serum erythropoietin/ ferritin levels at PGIMER, Chandigarh. A total of 1328 children were screened of which 402 children (stratified by age 4-17years) were identified as true native highlanders. Guardians of 12 children didn't consent for the haematological evaluation. Results: Study population included 197 males and 193 females. The mean age of study population was 127.58 + 39.64 months (range 35-254). The mean BMI was 18.7+2.5 kg/m2 (range 12.86-30.45). The mean peripheral oxygen saturation was 90.35 + 3.583 %. The haematological parameters of the study population are described in table 1. There was statistically significant difference between males and females in haemoglobin concentration, RBC count, haematocrit, platelet count and platelet distribution width (p

Description: Background: Acute promyelocytic leukemia (APML) is amongst the most curable malignancies with survival close to 80% [1]. Combination of all-trans- retinoic-acid (ATRA) and anthracyclines is the current standard of care for high-risk APML patients [2]. Literature on combination of arsenic trioxide (ATO) with ATRA in high risk APML, the number of cycles and long-term toxicity of ATO is scarce [3]. Methods: It is a single center retrospective study. Diagnosis of APML was made by bone marrow (BM) and PML-RARα detection by RT PCR. Patients with high risk APML (defined as TLC〉10000/µL) enrolled after 2006 were included and treated with combination of ATO/ATRA as per the protocol (Fig. 1). RT PCR for PML-RARα was done after remission induction, completion of consolidation and 6 monthly thereafter. Results: A total of 39 high risk APML patients were treated during the study period (25 males, 14 females) with median age 31y (range 15-50). Cohort was poorly educated (median - 10th standard) and were from poor socioeconomic strata (mean monthly income - INR 7000, 1USD=65INR). The major presenting complaints were bleeding manifestation and fever (78%, 84% respectively) for a median duration of 30 days (range 3-90d, 95% CI - 14.8). Baseline clinical, hematological and coagulation parameters are as enumerated in Table1.Table 1.Descriptive statistics high risk APML patients at baselineMinimumMaximumMeanStd. DeviationHeight (cm)148180163.109.91Weight (kg)35.080.055.4711.75Peripheral blood smear features at presentationHemoglobin (g/dL)4.113.37.132.36Leucocyte count (/µL)107001237004597635230.92Platelet ( x 109/L)625528944.76Blasts and Promyelocytes (%)010070.8535.57Bone marrow findings at diagnosisBlasts09417.5827.43Promyelocytes29670.2423.14Coagulation parameters at presentationPT (s)113120.104.22aPTT (s)203327.793.34Fibrinogen (g/L)0.683.841.890.81 Complications: DIC was present in 66.7% of the patient at baseline with the median duration to resolution of DIC on ATO/ATRA being 7 days (range 4 - 25d). Thrombosis was present in 17.1% of the patients. Differentiation syndrome (DS) was seen in 59% (n-23) of the patients at mean duration of 5.6 days of starting therapy (range: -4 to 14d). Twenty one percent of patients with DS (n-5) succumbed to death and all these patients had features of spontaneous DS prior to starting ATO/ATRA. Deaths due to differentiation were primarily seen in during the first week of starting therapy (median-D4). In rest all cases DS improved with dexamethasone 10mg BD and interruption of ATO/ATRA. Outcomes: Median duration to hematological remission was 31days (range: 2-59d). Bone marrow remission was attained in all patients alive at the end of induction. Molecular remission was attained in 100% of these patients. OS was 84.1% (Fig 2A). Log survival curve (Fig 2B) elucidates the fact that those patients who survived the induction therapy had no mortality further during the course of illness. Event free survival (EFS) was 84.1%, same as OS suggesting no patients relapsed during the therapy. Mean follow up of the cohort was 910 days (range 1 - 2681d, SD - 854.3d). Long term follow up these patients showed no evidence of secondary malignancy as feared by most authors for giving ATO therapy. Conclusions: Four cycles of ATRA/ATO with two years of maintenance therapy produces long-term remission with low risk of relapse and no arsenic induced long term toxicities in patients with high risk APML. REFERENCES: 1. Sanz MA, Lo-Coco F. Modern approaches to treating acute promyelocytic leukemia. J Clin Oncol 2011;29:495-503. 2. National Comprehensive Cancer Network (nccn). NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia. Ver. 2.2013. Fort Washington, PA: nccn; 2013. 3. Seftel MD, Barnett MJ, Couban S, Leber B, Storring J, Assaily W, Fuerth B, Christofides A, Schuh AC. A Canadian consensus on the management of newly diagnosed and relapsed acute promyelocytic leukemia in adults. Curr Oncol. 2014 Oct;21(5):234-50. Figure 1. Protocol of ATO/ATRA therapy. Legend: BM - Bone marrow, Consol - Consolidation, PCR - Polymerase chain reaction, DIC - disseminated intravascular coagulation, ANC - absolute neutrophil count, Wk - week, OD - once daily. Figure 1. Protocol of ATO/ATRA therapy. Legend: BM - Bone marrow, Consol - Consolidation, PCR - Polymerase chain reaction, DIC - disseminated intravascular coagulation, ANC - absolute neutrophil count, Wk - week, OD - once daily. Figure 2. Kaplan Meier curves (A) Cumulative survival curve showing 84% OS. (B) log survival curve showing no mortality after the initial 90 days after starting therapy. Figure 2. Kaplan Meier curves (A) Cumulative survival curve showing 84% OS. (B) log survival curve showing no mortality after the initial 90 days after starting therapy. Disclosures No relevant conflicts of interest to declare.

Description: Background: Autoimmune haemolytic anaemia (AIHA) is a relatively uncommon condition for acute fall in haemoglobin with grave consequences if not diagnosed and treated promptly. The literature on the clinical outcome, response to treatment, and occurrence of acute complications is relatively scarce from the real world. Aim: We retrospectively analysed 100 cases of autoimmune haemolytic anaemia (AIHA) for clinic-pathological features and response to therapy. Patients and methods: It is a single centre retrospective analysis of all cases of AIHA managed at our centre from Jan 2010- June 2016. Patients were analysed for the demographic features, presenting complaints, clinical/ pathological findings at diagnosis, types of therapy given and response to therapy. AIHA was diagnosed by features suggestive of haemolysis (anaemia with unconjugated hyperbilirubinemia, raised LDH and reticulocytosis) and/or positive DAT in the absence of any underlying secondary causes for anaemia according to the monospecific-DAT results and the thermal characteristics of the autoantibody, patients were classified as warm AIHA (DAT positive for IgG with or without C3D), cold agglutinin disease (DAT positive for C3D only with cold agglutinins), mixed (DAT positive for IgG and C3d with coexistence of warm autoantibodies and high titre cold agglutinins), or atypical AIHA (either DAT negative). Based on the severity of anaemia, patients were classified into very severe (Hb≤60gm/L), severe (Hb-61 to 80gm/L), moderate (Hb-81 to 100gm/L) and mild (Hb〉100gm/L). Results: A total of 100 consecutive patients were included fulfilling the inclusion criteria. The median follow-up of the study population was 17.7months (mean - 28.2m, range-0.3-197m). The median age of the patients was 33y (mean 36.3y: range 13-80y). There was female predominance (n=64, 64%). Easy fatiguability (85%) followed by dyspnoea on exertion (75%) were commonest presenting complaints. The median duration of complaints was 3 months (mean 8.93: range 0.2- 96). Jaundice (58%) and cola coloured urine (11%) were other important manifestations. Preceding history suggestive of viral infections was present in 22% of the patients and only one patient had significant drug history temporally correlating with AIHA. Splenomegaly was present in 67% with a median palpability of 2cm (mean 2.71: range 0- 20) and hepatomegaly in 49% with a median palpability of 1cm (mean 1.402: range 0 - 8) below the coastal margin. Lymphadenopathy was present in 8% of the patients. On severity grading 67% had very severe anaemia, 21% had severe, 9% moderate anaemia and 1% had mild anaemia. 24% of the patients had simultaneous low platelet counts less than 1 lakh. 17% patients had atypical AIHA - DAT negative. 21% patients had secondary AIHA of which eight patients had simultaneous low platelets (suggestive of Evans). The commonest cause for the secondary AIHA was rheumatological disorders (SLE 15 patients, MCTD one patient) followed by lymphomatous disorders in rest. Most common therapeutic modality employed was corticosteroids (methyl prednisolone pulse therapy n-20, prednisolone n-67), followed by IvIg (n-4), chemotherapy (RCHOP-1, RCVP-1, CVP-1) and rituximab (100mg/wk - 1, 375mg/m2/wk - 2). 75% of the patients had some clinical response (CR 47%, PR 22%, SD 6%) to the first line therapy. The median time to response was 1.5 months. 52% of the patients required repeat therapy in the form either steroid-sparing agent, immunosuppressant or repeat course of steroids. Six patients required splenectomy. The response to second-line therapy was seen in 92% of patients (CR 31/52, PR 9/52, SD 8/52). More than two lines/ times of therapy for non-response/relapse was required in 10% of the patients, of whom, 50% of the individuals were steroid dependent. A total of two patients succumbed to the illness (first owing to tuberculosis possible exacerbated by immunosuppressive therapy, and second due to progressive disease). Limitations of the study: All limitations of a retrospective study are applicable to our study as well. The selection of patients with fairer prognosis can explain a lower mortality in our study. Conclusion: Primary AIHA is the commonest form of AIHA. Most secondary AIHA has rheumatological etiology. Response to steroids is good leading to considerable remission but which is not long lasting and majority requiring second line/ second time therapy with same or alternative agents. Disclosures No relevant conflicts of interest to declare.

Description: 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.

Description: Introduction: The clinical behaviour and disease prognosis of AYA-CML is much different from adult CML. The outcome of this group of patients in resource constraints setting is not known where patients are seen in late chronic phase. Objectives: To study the survival pattern of AYA-CML in resource constraint settings. Methodology: It is a retrospective observational study wherein the data of all patients of AYA-CML managed at tertiary care centre in North India over last 14 years were analysed. All case records of the AYA-CML were perused, digitalised and their survival statistics derived. Results: Amongst a total of 1815 CML case records, 431 (23.74%) were AYA-CML. AYA-CML cases with complete data (n-225) were analysed for overall survival. The mean age of the patients was 23.08 ± 4.325 years (range 12-29). Males constituted 60.9% (n-137) and females, 39.1% (n-88) of AYA-CML. Of these 117 (52%) were single and 108 (48%) were married. Sixty one percentage of patients were educated upto 10th grade and 22.7% upto 5th grade and 8% received no formal education. Only 22.7% were educated beyond 12th grade. The mean monthly income was $75 (range $5-493). Ninety four percentage of patients had at least 12 months of follow up and 85.3% patients had at least 24 months of follow-up. The median delay in CML diagnosis from symptom onset was 62 days (range 0-2568). The details of therapy and complete haematological remission achieved in patients are described in table 1. The cumulative overall survival (OS) was 84% with no statistical difference in males and females (83.2%, 85.2% respectively) (Fig 1A, B). Survival rate at 1, 3, 5 and 8 years was 94.2%, 86.5% 78% and 74.2% respectively. Median OS was 1034 days (range 0-4788). OS was significantly better in patients receiving free drugs under Novartis Oncology Access (NOA) Program (p

Description: Introduction Acute lymphoblastic leukemia (ALL) diagnosed in adolescent and young adults (AYA) poses unique challenges. Despite using more intensive "pediatric-type" protocols, outcomes are generally inferior to those seen in children. The reasons are wide ranging, but when compared to pediatric ALL, AYA ALL has higher-risk biology, poorer tolerance to intensive treatments, and worse compliance with treatment regimens. India has one of the largest AYA populations in the world and AYA-ALL form a significant proportion of leukemias. The Indian acute leukemia research database [INwARD] was established in 2018 and had reported outcomes of ALLs from various centers of all age groups (Korula A, et al. Blood 2018 132:1374). Here, we present data focused on AYA-ALL from this database. Methods Retrospective data of AYA (15-29 years) patients with ALL (diagnosed between January 2012 to December 2017) from 9 centers were entered into an independent centralized online data capture system and analyzed for presenting characteristics, treatment and survival outcomes. Protocol choice was based on individual-center preference. For the purpose of this analysis, patients with WBC ≥30000 (B cell) and ≥100,000 (T-cell and other subtypes) were considered as high risk. Intensive protocols (MCP-841, BFM-95, COG), predominantly meant for children were labeled as "pediatric-type" and less intense protocols (GMALL, Hyper CVAD, UKALL) were considered as "adult-type". Results In the 6-year period, 1454 patients were registered [Males: 1114(76%), Median age: 20 years (15-29), Fig. 1.B; Subtype: B -ALL: 916(63%), T-ALL: 396 (27%); Fig. 1.C; High risk disease: 406 (28%)]. Of these,1100 (75%) underwent treatment. Poor financial support was the major reason for not taking treatment (Fig. 1.A). "Pediatric-type" protocols were used in 881 (81%) patients. After induction, 72% achieved complete remission (CR), 11% were refractory, 4% died during induction and 14% were not evaluable. Minimal residual disease was assessed in 581 and was present in 356 (61%). Attainment of CR, induction mortality, or MRD achievement was not affected by the type of regimen. Among these 1100 patients, 138 (12%) were lost to follow up and did not complete treatment. BCR ABL was tested in 636 and was positive in 112 (17%) [19% among patients with B-ALL (107/557)]and 106 of these were treated with additional tyrosine kinase inhibitors [imatinib (N=83) and dasatinib (N=23)]. Survival analysis: After a median follow up of 21 months, 270 patients relapsed [median time to relapse: 24 months (73% medullary, 17% CNS or testis, and 10% had a combined relapse) and 259 had died. The estimated 2-year event-free (EFS), relapse-free (RFS) and overall survival (OS) were 64%, 75% and 75% respectively. On univariate analysis the factors associated with inferior survival were as follows: EFS: WBC count ≥30,000/cmm, and ECOG PS 2-4; RFS: WBC count ≥30,000/cmm and ECOG PS 2-4; OS: use of "adult-type" protocols, ECOG PS 2-4, and BCR-ABL positive disease. On multivariate cox regression analysis, the only factors associated with inferior OS were: use of "adult" protocols (HR: 1.6), and BCR -ABL positive status (HR1.56) (Fig. 1.D). High WBC count at presentation predicted for inferior RFS while no factor could predict EFS on multivariate analysis. Conclusions In a multicenter analysis of AYA-ALL from different parts of India, we found that a quarter of newly diagnosed patients do not start treatment and another 12% are lost from follow up before treatment completion. Majority (80%) of the centers used "pediatric-type" protocols to treat AYA-ALL. Though superior survival was achieved with "pediatric-type" protocols, results must be interpreted with caution as these regimens were likely to be used more often in in younger patients. Variations in treatment protocols used between centers and the retrospective nature of the data are other caveats. Despite these limitations, this is one of the largest reports of AYA ALL from any part of the world and serves as a benchmark for planning prospective studies. Disclosures No relevant conflicts of interest to declare.

Description: 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