Impact of cognitive behavioural intervention on caregiver burden in mothers of children diagnosed with cancer.

Background: Mothers of children diagnosed with cancer are found to have coping difficulties in various studies. Most of the studies were done on parents after their child has been newly diagnosed with malignancy, and very few studies were done on coping skills intervention. Hence, this study has been done to assess the impact of cognitive behavioural intervention on caregiver burden in mothers of children diagnosed with cancer. Methods: Twenty mothers coming to the outpatient department of paediatric oncology from 01 September 2018 to 30 April 2019 were enrolled for the study. The participants were administered General Health Questionnaire, Brief Coping Operation Preference Enquiry Scale, Zung Self-Rating Anxiety Scale, and Coping Inventory for Stressful Situations-21 (CISS-21) Scale. Sixteen sessions of cognitive behavioural intervention were given over 8 weeks to all the participants. Reassessment was done after 3 months by use of the above mentioned scales. Results: Participants' mean anxiety score was 49.40 (standard deviation [SD] ±8.89). They used adaptive (active coping and positive reframing) more than the maladaptive (denial and self-blame) coping strategies. Task- and emotion-focused coping mean score on CISS-21 revealed 19.25 (SD ±6.20) and 18.90 (SD ±5.76), respectively. Reassessment after cognitive behavioural intervention revealed statistically significant improvement in maladaptive coping styles, mean anxiety index score, avoidance, and emotion-focused coping. Conclusion: The study has revealed mild to moderate anxiety and the use of both adaptive and maladaptive coping strategies by participants. There is statistically significant improvement in anxiety, maladaptive coping strategies with cognitive behavioural intervention.

Bone marrow transplant: A two-decade single centre hematology experience.

Background: Bone Marrow Transplant (BMT) is a curative form of therapy for many hematological disorders in both the adult and pediatric patients. The availability of BMT in the AFMS at AHRR for the last 02 decades has been a game changer for the patients. Methods: We reviewed our BMT data since the inception of the program till Feb 2023. Results: Over 700 patients with more than 23 different types of hematological disorders have undergone this procedure 58%% patients underwent an Autologous BMT and 42% an allogenic BMT. Autologous BMT for Multiple Myeloma and Allogenic BMT for Aplastic Anemia and Acute Leukemias have been the most common indications. 73% patients were adults, and 27% patients were of the pediatric age group. The male: female ratio was 2:1. The spectrum of allogenic Hematopoietic Stem Cell Transplant (HSCT) has expanded from Matched Sibling Donor (MSD) transplants to Matched Unrelated Donor (MUD) Transplants and Haploidentical Donor Transplants. 93% of our Allogenic BMT patients underwent a MSD BMT, 1% MUD BMT and 06% Haploidentical BMT. Today no patient with a malignant hematological disorder requiring a BMT is denied the procedure due to the lack of an HLA donor due to the availability of haploidentical BMT. Conclusion: The evolution of a BMT program has a long learning curve and the expanded pool of eligible donors has led to a situation of "transplant for all". Haploidentical HSCT for nonmalignant hematological disorders is an unmet need. CART cell therapy and Cellular therapies need to be prioritized for future inclusion.

Real-world experience of anti-D immunoglobulin in immune thrombocytopenia.

In developing countries, anti-D has been used in immune thrombocytopenia (ITP) as a cheaper alternative to human immunoglobulin. We aim to analyze the response and safety profile of anti-D in patients with severe ITP. A retrospective study was conducted at a tertiary care hospital in Northern India. Patients received a single intravenous infusion of 75 µg/kg anti-D. In total, 36 patients (20 females) were included in this study. The median duration from ITP diagnosis to anti-D therapy was 235 days (range 1-1613 days). Four (11.1%) patients received anti-D as an upfront treatment. The patients' platelet counts rose significantly by the end of day three and continued to be significantly high until day 30 of receiving anti-D (p ≤ 0.001). The overall response rate (ORR) by day seven was 88.89%. There was no effect of age, sex, duration of disease, prior therapy, and platelet count on the ORR. Patients were followed up for a median duration of 52 days (longest follow-up: 3080 days). Six (6/36, 16.67%) patients continued to be in remission till the last follow-up. The hemoglobin fall was statistically significant on day three and day seven (p < 0.001 and p = 0.001) and got normalized by day 30. We observed equally good ORR in mixed populations and different phases of ITP along with long-term sustained response. The study demonstrates a quick and high response rate along with good safety profile to anti-D in all forms of ITP.

Association of CD 34 positive cell dose with engraftment kinetics in autologous peripheral blood stem cell transplant patients of multiple myeloma.

Background: Treatment with high-dose chemotherapy and stem cell transplantation has prolonged survival in patients of multiple myeloma (MM). A dose-response relationship between number of CD34+ cells infused and leukocyte and platelet recovery, exists. Patients receiving dose of <2.0 × 106 CD34+ cells/kg have delayed engraftment. The level of optimal cutoff for accelerated engraftment is yet to be validated. Hence, this study was undertaken to study the association of CD 34+ cell dose with engraftment kinetics in patients of MM who underwent autolgous peripheral blood stem cell transplant (PBSCT). Methods: We retrospectively analyzed 19 patients of MM who underwent PBSCT at our center between December 2016 to December 2018. Complete blood counts were carried out daily after transplantation to record neutrophil and platelet engraftment. Results: Based on the CD34+ cell dose given : <5 × 106/kg (category 1), 5-10 × 106/kg (category 2), >5 × 106/kg (category 3), the mean (SD) neutrophil engraftment time was 11.3 (0.5) days, 10.6 (0.9) days, and 10.2 (1.3) days respectively. Platelet engraftment time was 12.4 (2.60) days, 10.6 (1.14) days, and 11.2 (1.64) days for category 1, 2, and 3 patients, respectively. Correlation co-efficient between CD 34+cell dose and days for neutrophil and platelet engraftment was found to be -0.24 and -0.20, respectively. Time for neutrophil engraftment was found to be significantly associated with CD34+ cell dose category. Conclusion: CD 34+ cell dose appears as the strongest predictor of leukocyte and platelet engraftment. CD 34+ cell dose of >5.0 × 106 cells/kg leads to an accelerated neutrophil and platelet engraftment in patients of MM.

A study on DNA methylation status in promoter region of p15 gene in patients of acute myeloid leukemia and myelodysplastic syndrome.

BACKGROUND: Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) are a spectrum of hematological malignancies with a multistep process of accumulated genetic and epigenetic alterations. DNA methylation is most extensively studied epigenetic alteration in malignancies. Recent research studies in the field have brought out translational implications of promoter methylation of tumor suppressor gene p15 in tumors. Therefore, we studied the role of DNA Methylation of p15 gene in AML and MDS. METHODS: The study was carried out in 41 consecutive AML/MDS cases reporting to hematological OPD of a tertiary care center along with 25 age and sex-matched healthy controls. The methylation status in the promoter region of the p15 gene was assessed by methylation-specific PCR (MSP) from blood samples after ethical approval and informed consent of the patients and controls. The association of methylation status was studied with clinical presentations, AML subtypes, and cytogenetics using Chi-square test/Fisher's exact test tools. RESULTS: A total of 41 cases included in the study comprised 33 cases of AML and 08 cases of MDS with an age range between 06 months and 82 years. Of the 41 cases, 29 revealed promoter methylation of the p15 gene, which compared to healthy controls was found statistically significant (p < 0.001). The methylation status did not significantly correlate with AML subtypes or the cytogenetic abnormalities detected in cases. CONCLUSION: The outcome of the study indicates p15 promoter DNA methylation in cases of AML and MDS may identify those individuals who might benefit from the targeted therapeutic approaches.

Gut microbiota profiling in hematopoietic stem cell transplant recipients: Towards personalized medicine.

BACKGROUND: Antibiotic resistance in bacteria is a cause for concern, especially in hematopoietic stem cell transplant (HSCT) patients. Endogenous bowel microflora in HSCT patients get replaced by hospital multidrug resistant flora and pose risk of serious bacterial infection during the pre-engraftment stage. For decades, many methods to reduce the translocation of gut microbiota in HSCT patients have been attempted. Despite the logic, of using prophylactic antibiotics, there is no consensus on standard regimen. Personalized antibiotic prophylaxis-based on gut microbiota and clinical profile has been suggested by researchers. In this study, gut microbiota in HSCT recipients has been studied with antimicrobial susceptibility testing and detection of various antibiotic resistance phenotypes. METHODS: Seventy-six HSCT patients (2016-2018) were included. Stool surveillance cultures and antibiotic susceptibility testing were performed. Bacterial isolates were classified into various antibiotic resistance phenotypes. RESULTS: This study revealed that 73.75% HSCT recipients had gut colonized with antibiotic resistance microbiota which included extended-spectrum ß-lactamase-, multidrug- and extensively drug-resistant phenotypes. CONCLUSION: This study reiterates the importance of individual profiling of gut microbiota in HSCT patients.

A descriptive study of clinico-hematological profile of megaloblastic anemia in a tertiary care hospital.

BACKGROUND: Megaloblastic Anemia (MA) is a relatively common disease, yet the data on prevalence of MA remains scarce. This study was conducted to study the prevalence and clinico-hematological profile of MA. METHODS: This was a cross-sectional study done on 1150 adult anemic patients. All patients diagnosed to have MA were studied for clinico-hematological and etiological profile. Nerve conduction studies (NCS) were done in all. RESULTS: MA was present in 3.6% cases of anemia. Severe anemia was seen in 9.7% of anemic patients and 75% of MA cases (p < 0.05). Forty five percent of MA patients presented with pancytopenia. Vitamin B12 and folic acid deficiency were documented in 40% and 25% cases respectively while combined deficiency was noted in 35% of all MA cases. There was no co-relation between severity of anemia and deficiency of either of the vitamins (Fischer exact test: 0.530). Among MA patients, 35% were vegetarians while 65% consumed mixed diet. There was no association between vegetarian diet and Vit B12 deficiency (p = 0.3137). An additional etiology was more commonly found in patients on mixed diet [92%; 24/26] as compared to those on vegetarian diet [50%; 7/14] (p = 0.04). NCS was abnormal in 14 patients (35%). Overt clinical neuropathy was present in 12 cases of MA, while subclinical neuropathy was seen in 2 cases. CONCLUSION: MA is one of common causes of pancytopenia and severe anemia. Diet plays an important role in causation of MA in vegetarians. An alternative etiology is however, more likely to be found in patients on mixed diet. While overt neurological abnormalities are common in MA, subclinical neuropathy is uncommon.

Flowcytometric comparative analysis in acute leukemias between Indian and proposed minimal screening panel.

BACKGROUND: Acute myeloid leukemia and acute lymphoid leukemia differ substantially in response to therapy and course, and accurate differentiation of the two is fundamental to therapeutic decisions. Immunophenotyping is used for this purpose, and various guidelines have been proposed regarding a minimal screening antibody panel. Most of them have been found inefficient. METHODS: Eighty-two cases of consecutive acute leukemias reporting to this hospital over a period of two years were included in the study. Peripheral blood smear, bone marrow aspirate, and bone marrow biopsy were studied using morphology, cytochemical stains, and relevant immunohistochemical stains on selected biopsy specimens. Flowcytometry analysis was carried out using Indian consensus screening panel and our proposed minimal screening panel (PMSP) for comparison. RESULT: Immunophenotyping using PMSP resulted in 95.12% accurate diagnosis versus Indian consensus minimal screening panel (ICMSP) with an accuracy of 92.68%. This result was statistically significant as per Chi Square tests. CONCLUSION: PMSP can be used as a substitute for ICMSP, since it includes lineage-specific cytoplasmic antibodies, as well as lesser number of monoclonal antibodies, and enables us to diagnose mixed lineage leukemia. Fewer markers can be linked to a lower cost as well, which is relevant in a developing economy.

Monitoring of response to therapy with imatinib mesylate in Chronic Myeloid Leukemia in chronic phase (CML-CP).

BACKGROUND: The BCR-ABL tyrosine kinase is a well validated therapeutic target in Chronic Myeloid Leukemia (CML). Imatinib mesylate (IM), a tyrosine kinase inhibitor is highly effective in the treatment of chronic phase CML. BCR - ABL transcripts have been well established as a molecular marker to document response to therapy in CML. Periodic monitoring of this marker helps in evolving therapeutic strategies with IM and also in diagnosing early relapse. This study was undertaken to monitor therapeutic response to IM in CML in chronic phase (CML-CP) by assessing BCR-ABL by real time quantitative PCR (RQ-PCR) techniques and to determine the effectiveness of the Indian generic IM. METHODS: One hundred consecutive patients of CML in chronic phase (CML-CP) were treated with an Indian generic of IM. Eighty-five patients were evaluable at 12 months of therapy. At entry, diagnosis of CML-CP was confirmed by FISH and RQ-PCR. Response to therapy was monitored by assessing BCR-ABL levels by RQ-PCR at 6 and 12 months of therapy. Regular follow up of patients was done to evaluate the safety profile of IM used in these patients. RESULTS: Complete hematological response (CHR) rates at 3, 6, 9 and 12 months were 92%, 94%, 100% and 100% respectively. The total molecular response at 12 months was 43.52% of which complete molecular response (CMR) was noted in 17.64% and major molecular response (MMR) was observed in 25.88%. A cumulative survival probability of 0.8 was observed. CONCLUSION: The Indian generic molecule of IM is effective in the treatment of CML-CP. The cost of Indian generic molecule is less than Rs. 10,000 per month there by making this affordable for large number of CML-CP patients in India.

Integrative proteome analysis of bone marrow interstitial fluid and serum reveals candidate signature for acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive form of blood cancer and clinically highly heterogeneous characterized by the accumulation of clonally proliferative immature precursors of myeloid lineage leading to bone marrow failure. Although, the current diagnostic methods for AML consist of cytogenetic and molecular assessment, there is a need for new markers that can serve as useful candidates in diagnosis, prognosis and understanding the pathophysiology of the disease. This study involves the investigation of alterations in the bone marrow interstitial fluid and serum proteome of AML patients compared to controls using label-free quantitative proteomic approach. A total of 201 differentially abundant proteins were identified in AML BMIF, while in the case of serum 123 differentially abundant proteins were identified. The bioinformatics analysis performed using IPA revealed several altered pathways including FAK signalling, IL-12 signalling and production of macrophages etc. Verification experiments were performed in a fresh independent cohort of samples using MRM assays led to the identification of a panel of three proteins viz., PPBP, APOH, ENOA which were further validated in a new cohort of serum samples by ELISA. The three-protein panel could be helpful in the diagnosis, prognosis and understanding of the pathophysiology of AML in the future. BIOLOGICAL SIGNIFICANCE: Acute Myeloid Leukemia (AML) is a type haematological malignancy which constitute one third of total leukemias and it is the most common acute leukemia in adults. In the current clinical practice, the evaluation of diagnosis and progression of AML is largely based on morphologic, immunophenotypic, cytogenetic and molecular assessment. There is a need for new markers/signatures which can serve as useful candidates in diagnosis and prognosis. The present study aims to identify and validate candidate biosignature for AML which can be useful in diagnosis, prognosis and understand the pathophysiology of the disease. Here, we identified 201 altered proteins in AML BMIF and 123 in serum. Among these altered proteins, a set of three proteins viz., pro-platelet basic protein (CXCL7), enolase 1 (ENO1) and beta-2-glycoprotein 1 (APOH) were significantly increased in AML BMIF and serum suggest that this panel of proteins could help in future AML disease management and thereby improving the survival expectancy of AML patients.

The use of a fludarabine-based conditioning regimen in patients with severe aplastic anemia--a retrospective analysis from three Indian centers.

Between 2001 and 2009, 121 patients with severe aplastic anemia (SAA) underwent hematopoietic stem cell transplantation (HSCT) using a conditioning protocol of fludarabine and cyclophosphamide at three Indian hospitals. Donors were HLA-identical sibling or family donors. Seventy-six patients were considered "high risk" as per criteria. The graft source included peripheral blood stem cells in 109 and G-CSF-stimulated bone marrow in 12. GVHD prophylaxis consisted of cyclosporine and mini-methotrexate. Engraftment occurred in 117 (96.6%) while two had graft failure and two expired in the first two wk. Neutrophil engraftment was seen at 12.3 d (range: 9-19) while platelet engraftment occurred at 12.4 d (range: 8-32). Grade II-IV acute GVHD was seen in 26.7% and grade IV GVHD in 8.6%. Chronic GVHD occurred in 44% and was extensive in 10%. The five-yr overall survival for the entire cohort is 75.8 ± 3.9% with a survival of 95.6 ± 3.1% in the low-risk group (n = 45) and 64.0 ± 5.6% in the high-risk group (n = 76). Conditioning with fludarabine and cyclophosphamide is associated with very good long-term survival in patients undergoing HSCT for SAA.

Immunosuppressive therapy in adults with aplastic anaemia: single-institution experience from India.

OBJECTIVE: To determine overall survival and factors predicting survival after immunosuppressive therapy in patients with acquired aplastic anaemia. DESIGN: Retrospective. SETTING: Tertiary care hospital. PATIENTS: 120 adults diagnosed as having acquired aplastic anaemia between 1 January 1996 and 31 December 2009. INTERVENTIONS: Anti-thymocyte globulin (ATG) followed by ciclosporin was administered to all patients for 15-18 months as the initial treatment. Haematological response was assessed 6 months after ATG administration and 6-monthly thereafter. Platelets were transfused if levels were <10 × 10(3)/l and for symptomatic bleeding. Transfusions of red blood cells were given for haemoglobin levels <70 g/l or symptomatic anaemia. Febrile neutropenia was managed with antibiotics, with the addition of antifungal agents after 3-4 days of unresponsive fever. Granulocyte colony-stimulating factor was administered at a dose of 5 µg/kg/day (maximum 300 µg/day) subcutaneously for infective episodes. PRIMARY OUTCOME: overall survival. Secondary outcome: response to immunosuppressive therapy, failure-free survival, relapse and clonal evolutions. The response and relapse criteria were defined in accordance with the British Council for Standards in Haematology guidelines. RESULTS: Overall response at 6 months after initiation of treatment was 85.8% (103/120). Overall survival at 76 months was 83.4%. Overall survival correlated with presence of response (complete response or partial response) at 6 months after ATG administration (HR=0.021, 95% CI 0.006 to 0.079, p<0.001). The occurrence of infectious complications adversely affected the overall survival (HR=5.71, 95% CI 1.22 to 26.77, p=0.027). Six patients relapsed. There were no deaths or adverse events 12 months after treatment among responders. CONCLUSIONS: In our study, overall survival was 83.4% at a median follow-up of 76 months. The two variables that significantly affected overall survival were response to therapy at 6 months and occurrence of infectious complications.

A clinicopathological analysis of 26 patients with infection-associated haemophagocytic lymphohistiocytosis and the importance of bone marrow phagocytosis for the early initiation of immunomodulatory treatment.

OBJECTIVE: To analyse the clinicopathological presentation, outcome and importance of bone marrow haemophagocytosis in patients with infection-associated haemophagocytic lymphohistiocytosis (IA-HLH) in a tertiary care hospital in Northern India. STUDY DESIGN: Between January 2007 and December 2009, 26 consecutive patients meeting the diagnostic criteria for IA-HLH, based on the HLH2004 protocol of the Histiocyte Society, were followed up for between 12 and 34 months (median 20 months). RESULTS: IA-HLH was diagnosed in three of the five patients who died 5-6 weeks after the onset of the illness, whereas diagnosis in the remaining group was made a median of 2 weeks after the onset of the illness. The predominant presenting features were fever (100%), hepatomegaly (69%), splenomegaly (58%) and anaemia (96%). All patients showed >3% haemophagocytosis on bone marrow studies-in four cases after serial aspiration/biopsies. Twenty-one (80.8%) cases were non-fatal and five (19.2%) patients died. The non-fatal cases included eight (38.1%) cases of viral infection, seven (33.3%) bacterial infections, two (9.6%) fungal and four (19.0%) protozoal infections; whereas four (80%) bacterial infections and one (20%) viral infection were associated with the fatal cases. The mean of the nadir blood counts of white blood cells, absolute neutrophil counts and platelets; the mean of all the peak biochemical parameters of liver function tests, lactate dehydrogenase and ferritin and the lowest fibrinogen values before treatment, differed significantly (p<0.05) between the non-fatal and the fatal group, being worse in the latter. CONCLUSIONS: IA-HLH is important because it can obscure the typical clinical features of the underlying primary disease, thus delaying the diagnosis and having a negative effect on the outcome. Although bone marrow haemophagocytosis is not a mandatory diagnostic criterion, we found it to be a useful tool together with biochemical parameters for early recognition of HLH, especially in developing countries lacking molecular and flow laboratories. The severity of pancytopenia and derangement in biochemical markers were significantly higher in the patients who died.

Supplemental Pioglitazone to Patients of CML with Suboptimal TKI Response: A Pragmatic Pilot Study.

Tyrosine kinase inhibitors (TKIs) have improved outcomes of chronic myeloid leukemia (CML). However, 20-30% of patients require second-line TKIs following suboptimal response. The cost and adverse events limit their use in resource-constraint settings. We conducted a pilot study to ascertain the benefit of adding pioglitazone to TKIs with suboptimal response in real-world resource-constraint settings. In this pragmatic pilot study from 01 Jan 2017 to 31 July 2021, CML patients from a tertiary care center in North India with sub-optimal response to TKIs were additionally given pioglitazone after ruling out imatinib resistance mutation (n - 31). Pioglitazone was stopped if there was disease progression on follow-up, and second-line TKI was started. The data were analyzed with the intention-to-treat principle using JMP Ver.15.1.1. The median age of the study population was 54y (27-82), who were followed up for a median duration of 1023.5d (59-1117). Pioglitazone showed the benefit of one-log reduction in BCR-ABL in 89.7% of the study participants. 1y, 2y and 3y-PFS were 92.57%, 76.5%, and 68.3% respectively. During follow-up period, the disease progressed in 38.7%, of which two succumbed. No adverse events to Pioglitazone were documented. This study proved that adding Pioglitazone to the existing TKI regime in CML with sub-optimal response can benefit. The addition of Pioglitazone was well tolerated. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01561-x.

A retrospective study to assess the impact of ABO incompatibility on outcomes of allogeneic peripheral blood stem cell transplants at a tertiary care hospital in Western Maharashtra.

BACKGROUND: Hematopoietic stem cell transplantation (HSCT) has emerged as a curative measure for life-threatening hematological disorders. It can be autologous or allogeneic depending on the disease characteristics. Providing transfusion support to the transplant patients can be challenging, especially in AB-mismatched allogeneic HSCT. In this study, we investigated the impact of ABO incompatibility in patients undergoing allogeneic HSCT. MATERIALS AND METHODS: A retrospective review was conducted in 76 patients with hematological diseases who underwent allogeneic HSCT. Transfusion requirements, engraftment profile, incidence of graft versus host disease (GvHD), and mortality for a period of 1 year were analyzed. RESULTS: ABO incompatibility between donor and the patient did not significantly affect the neutrophil and platelet (PLT) engraftment time (P = 0.389, 0.349, respectively), packed red blood cells transfusion requirement, and duration of initial hospital stay. However, patients of ABO-incompatible HSCT received more PLT transfusions posttransplant which was statistically significant. 29.1% of ABO compatible and 16.7% incompatible HSCT patients developed GVHD. Mortality rates in the two groups were 16.7% and 8.3%, respectively. However, differences in both the parameters were not statistically significant. CONCLUSION: Our study showed that ABO incompatibility does not significantly affect the outcome and should not be a limiting factor for selection of donor. Donor availability and human leukocyte antigen (HLA) matching remain the critical selection criteria.

Isolated CNS relapse in FLT 3 mutation positive CMML post allogeneic stem cell transplant: Report of a rare case.

Chronic myelomonocytic leukemia is a clonal chronic hematopoietic disorder that has been classified under the category of Myelodysplastic syndrome/Myeloproliferative neoplasms (MDS/MPN). CMML has high chances of transforming to acute leukemia, however isolated CNS relapse in CMML has never been reported in literature. We report an extremely rare case of a 47 yearold female diagnosed to have CMML- 2 in remission, who developed an isolated central nervous system relapse after matched related allogeneic hematopoietic stem cell transplantation. To our knowledge this is the first report of isolated CNS relapse in CMML post allogeneic stem cell transplant.

Isolated CNS Relapse in Acute Lymphoblastic Leukemia (ALL): An Experience from a Tertiary Care Center.

Aims and Objectives In this study the various parameters of acute lymphoblastic leukemia (ALL), including the clinical features, peripheral blood and bone marrow (BM) findings, immunophenotypic and cytogenetic details in ALL cases who had isolated relapse involving the central nervous system (CNS), were studied. Patients/Materials and Methods Duration of the study is from 2015 to 2019 in which 5 ALL cases were presented to this tertiary care center. The presenting symptoms varied from headache, fever, and distension of abdomen. These cases were either on therapy or post completion of chemotherapy. The diagnosis of CNS relapse followed after the examination of cerebrospinal fluid (CSF). Patients also underwent BM examination to rule out systemic relapse. Results Age of patients ranged from 7 months to 42 years. There were three female patients. Two patients had isolated CNS relapse 3.5 years after completing therapy and succumbed to their illness. Two patients had t(9;22) while one patient had t(1;14) cytogenetic abnormality at diagnosis. One patient was diagnosed as T-ALL. Treatment offered was German Multicentre ALL protocol for induction along with 10 cycles of maintenance. Conclusion The most common hematolymphoid malignancy in children namely ALL accounts for 75% of childhood leukemias. Complete remission rates reach up to 70 to 80%. CNS involvement is known to occur in these cases. CNS relapse may occur alone or with systemic relapse. Advances in therapeutic protocols along with CNS prophylaxis have drastically brought down the rates of CNS relapse. It is essential to maintain a high degree of suspicion so that these cases of isolated CNS relapse can be identified at the earliest and definitive therapy can be offered.

Survival Outcomes of Newly Diagnosed Multiple Myeloma at a Tertiary Care Center in North India (IMAGe: 001A Study).

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.

Safety and efficacy of azathioprine in immune thrombocytopenia.

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.

Safety and efficacy of splenectomy in immune thrombocytopenia.

BACKGROUND: Immune Thrombocytopenia (ITP) is characterized by low platelet counts. Splenectomy has been in practice for the treatment of ITP since the early 20th century. We aimed to analyze the data of ITP patients from our hospital who underwent splenectomy and further present the long-term outcome and safety profile in these patients. METHOD: This study was a single-center, registry based study conducted at a tertiary care hospital in Northern India. Patients aged 18 years or more, who underwent splenectomy after at least one line of therapy, were included in the study. The primary outcome was the overall response rate (ORR) at one month after splenectomy. Secondary outcomes were sustained response, relapse-free survival, factors affecting the ORR, and adverse events after splenectomy. RESULTS: Forty-five patients of ITP were included in the study. Thirty-six patients underwent splenectomy in the first half (2001-2010), of the study period. The median age of the patients was 38 (19-56) years. The median duration from diagnosis to splenectomy was 1.76 (0.47-2.58) years. The median number of therapy received before splenectomy was 3 (1-6). The overall response rate (ORR) post-splenectomy at day 30 was 89.2% with 61.8% complete response (CR). The ORR was 88.5% at 1-year, with 48.8% CR. The relapse-free survival (RFS) at 5-years was 57.38% (95% Confidence Interval 40.59-71.02%), There was no effect of duration of disease, age, gender, and prior therapy received, on the ORR at one-month. At one year, the platelet response was significantly better in patients who had a CR at one-month than patients who had a partial response at one month. The relapse-free survival was better in patients who achieved CR after 1-month of splenectomy. During the median follow-up of 5.02 (1 month-20 years) years, there were five cases of overwhelming post-splenectomy infection (OPSI). There was no recorded incidence of perioperative mortality, deep vein thrombosis, or mesenteric thrombosis. DISCUSSION: Despite the variation in outcome from different studies, splenectomy gives the best possible long-term treatment-free remission amongst all the available second-line agents. It is also, one of the most financially affordable therapies. Despite advantages, the number of ITP patients undergoing splenectomy has been on the decline and largely attributable to the newer and more effective second-line therapies. There is no pre-surgery variable predicting the ORR after splenectomy. CONCLUSION: Splenectomy in ITP offers a long-term sustained response at an economical cost.