Real world outcome of B ALL with t (1; 19) (q23; p13)/TCF3::PBX1 in adolescents and adults treated with intensive regimes.

Significant heterogeneity has been reported in outcome of Acute lymphoblastic leukemia with t(1;19)(q23;p13)/TCF3::PBX1 in adolescents and adults leading to a lack of consensus on precise risk stratification. We evaluated clinical outcome of 17 adult ALL cases (≥15 years) with this genotype treated on intensive regimes.13/17 received COG0232 and 4/17 cases received UK-ALL protocol. All achieved CR (100%) with above treatment. End of induction MRD was evaluated in 14/17 cases of which 11 (78.5%) achieved MRD negativity. Total nine patients relapsed (7 marrows, 2 CNS). Overall survival at 2 years was 53.3%. The 2 year estimated PFS was 42.9%. The 2 years CIR was 54.2%. Adults with this genotype perform poorly despite early favorable response. Incorporation of novel immunotherapies and prompt HSCT should be strongly considered with this genotype. Targeted NGS panels for additional genetic aberrations can further help in risk stratifying and guiding therapy for this genotype.

Immunophenotypic Profile of Multiple Myeloma: A Tertiary Care Centre Experience.

Background Immunophenotyping and enumeration of plasma cells (PCs) by flow cytometry are deemed to be prognostically significant. However, PCs enumeration by flow cytometry is challenging owing to discrepancy with morphology and PCs loss during sample processing. Enumeration and differentiation of abnormal plasma cells (APCs) and normal plasma cells (NPCs) is difficult because abnormal antigen expression can be seen in subsets of NPCs. This is particularly true when a limited panel of antibodies are relied upon. Aims and purpose To study the immunophenotypic profile of newly diagnosed multiple myeloma (MM) cases by flow cytometry and evaluate the sensitivities and specificities of individual antigens and combinations. Methods We studied immunophenotype of PCs in newly diagnosed MM cases ( n = 48) and control cases ( n = 10) by a 6-color, 3-tube flow cytometry panel. The sensitivities and specificities of antigens in MM were evaluated and compared with control cases. Results Majority of MM cases ( n = 43) had < 3% NPCs. CD19 was the most sensitive (100%) and CD81 was the most specific marker (100%) for differentiating APCs from NPCs. CD38 MFI came out as a useful marker for APCs identification. In combination, CD19 and CD81 had a higher sensitivity and specificity to detect APCs. Conclusion NPCs may show aberrant antigen expression. A combination of multiple markers including CD81 and CD38 MFI should be used for accurate APC detection.

Prospective identification of potential factors influencing stem cell mobilization and the necessity for plerixafor use in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation

ABSTRACT Introduction: To study the efficacy and safety of single large volume leukapheresis by using generic G-CSF or G-CSF plus Plerixafor in achieving adequate stem cell yield and various factors influencing thereof in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant . Method: This prospective study was undertaken among 55 newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant and aged between 18 and 75 years. Mobilization and harvesting of stem cells were performed by using GCSF or GCSF plus Plerixafor and large volume leukapheresis, respectively. A stem cell yield of ≥2 × 106 kg-1 and the number of apheresis procedures were primary efficacy endpoints, while the ideal stem cells yield >5 × 106 kg-1, the engraftment day and D100 response/graft sustainability were secondary endpoints. Result: The primary endpoint was achieved in all cases in both the groups by using a single LVL leukapheresis procedure. Fulfillment of all the secondary endpoints was satisfactory and comparable in both the groups. Age, pre-apheresis CD34+ count and number of interruptions during the LVL were significant factors influencing the stem cell yield (p < 0.05). Adverse drug reactions during the apheresis and post-ASCT period were manageable. Conclusion: The LVL is safe and cost-effective in attaining a minimum of CD34+ cells in a single procedure with manageable adverse reactions. Judicious intervention during the procedure may be helpful in ensuring the adequate yield.

Hypercalcaemia, renal failure, anaemia and osteolytic lesions (CRAB) in chronic lymphocytic leukaemia mimicking multiple myeloma.

Classical CRAB features (hypercalcaemia, renal failure, anaemia, osteolytic lesions) have been traditionally defined in patients with plasma cell dyscrasia. But these can be rare and uncommon presentations of other chronic lymphoproliferative disorders (CLPD). The pathophysiological basis of CRAB features in other CLPD need to be explored further for better outcomes and therapeutic interventions. These can present a diagnostic dilemma and requires extensive workup to rule out coexisting malignancy and myeloma. Here, we report an unusual case of B CLPD in a middle-aged male who presented with classical CRAB features along with a brief literature review. After detailed investigations, he was diagnosed as chronic lymphocytic leukaemia, without any second malignancy and responded well to ibrutinib-based therapy.

Prospective identification of potential factors influencing stem cell mobilization and the necessity for plerixafor use in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplantation.

INTRODUCTION: To study the efficacy and safety of single large volume leukapheresis by using generic G-CSF or G-CSF plus Plerixafor in achieving adequate stem cell yield and various factors influencing thereof in newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant . METHOD: This prospective study was undertaken among 55 newly diagnosed multiple myeloma patients undergoing autologous stem cell transplant and aged between 18 and 75 years. Mobilization and harvesting of stem cells were performed by using GCSF or GCSF plus Plerixafor and large volume leukapheresis, respectively. A stem cell yield of ≥2×106kg-1 and the number of apheresis procedures were primary efficacy endpoints, while the ideal stem cells yield >5×106kg-1, the engraftment day and D100 response/graft sustainability were secondary endpoints. RESULT: The primary endpoint was achieved in all cases in both the groups by using a single LVL leukapheresis procedure. Fulfillment of all the secondary endpoints was satisfactory and comparable in both the groups. Age, pre-apheresis CD34+ count and number of interruptions during the LVL were significant factors influencing the stem cell yield (p<0.05). Adverse drug reactions during the apheresis and post-ASCT period were manageable. CONCLUSION: The LVL is safe and cost-effective in attaining a minimum of CD34+ cells in a single procedure with manageable adverse reactions. Judicious intervention during the procedure may be helpful in ensuring the adequate yield.

Tele-Medicine Services in Hematological Practice During Covid Pandemic: Its Feasibility and Difficulties.

In COVID 19 pandemic, delivery and access of health care services have become challenging. Telemedicine services can be considered for management of patients with hematological diseases. This study included all patients who enrolled for telemedicine facility for hematology from May 15 to July 15, 2020. Patient's demographic and disease related parameters were recorded during the teleconsultation call. Overall satisfaction of attending doctor and patients were also recorded. A total of 1187 teleconsultation appointments were taken, of which 944 (79.6%) were successfully attended. Median age of patients was 38 years (range- 0.5-78 years), with 38% females. 55% of successful calls were from patients suffering a malignant hematological disorder. 24% had an active complaint pertaining to their disease or treatment. Of these, 162 (17%) were asked for a physical consultation. A significant association was found between the requirement of physical consultation and diagnosis (p < 0.001), absence of active complaint (< 0.0001) and education level of responder (p = 0.008). Patients understand that teleconsultation is helpful in preventing COVID-19 infection (71.4%) and avoids outpatient department rush (14.5%) associated with physical appointments; and around 80% patients were satisfied with the teleconsult. With the emergence of COVID 19, many localities under partial lockdown with constant fear of contacting virus amongst patients and health care providers, we can clearly see the advantages as well as feasibility of telemedicine services for our patients. The acute surge in telemedicine could be harnessed in the future to provide comprehensive and integrated care to patients of hematological disorders.

Hematological, Biochemical and Renal Changes in Patients of Multiple Myeloma Treated with Bortezomib Based Triple Drug Chemotherapy.

INTRODUCTION: Multiple myeloma (MM) is a neoplastic clonal plasma cell disorder. Approximately 30% of newly diagnosed MM present with baseline renal dysfunction adversely affecting prognosis and survival. But its outcome has improved with the advent of novel agents. METHODS: We undertook this clinicopathological study to assess the profile of renal involvement, evaluate hematological response, renal reversibility and renal response of 34 newly diagnosed cases of MM with renal impairment receiving 4-6 cycles of Bortezomib, Thalidomide and Dexamethasone (BTD). RESULTS: Bone pain (67.64%) and pallor (88.23%) were the most common clinical symptom and sign respectively. Mean serum creatinine before and after treatment was 3.5 mg/dl and 1.59 mg/dl respectively. After treatment 15 cases achieved renal reversibility, 8 patients had improved renal function and 3 patients became dialysis independent. The median time to renal reversal was 22weeks (2-28 weeks) and overall myeloma response rate was 78.78%. All patients showed renal response. The median time to renal response was 2.4weeks. We found 38.23% pure cast nephropathy, 14.7% myeloma immunoglobulin deposition disease (MIDD), 5.88% amylodosis apart from other lesions. CONCLUSION: BTD is safe, effective in reversing renal impairment and improves survival in newly diagnosed cases of MM with renal impairment.

Beneficial Effect of Low Fixed Dose of Hydroxyurea in Vaso-occlusive Crisis and Transfusion Requirements in Adult HbSS Patients: A Prospective Study in a Tertiary Care Center.

Significant reduction in morbidity and mortality have been documented in patients with sickle cell disease (HbSS) by most of the studies using hydroxyurea at a dose of 25-35 mg/kg/day or maximum tolerated dose. But toxicities, need for frequent monitoring, compliance and cost are important hurdles particularly in Indian set up. We undertook this study to find out the efficacy, safety compliance rate of low fixed dose of hydroxyurea (10 mg/kg/day) in patients presenting to our hospital and its impact on clinical profile and laboratory parameters. A cohort of 128 (82 males, 46 females) confirmed HbSS cases (each >18 years age, vaso-occlusive crisis >2/years and/ or rate of transfusion 1-2 units/month) with no disease related end organ damage were assessed prospectively between 2013 and 2016. They were started on 10 mg/kg/day hydroxyurea along with other supportive care and followed up monthly for 1 year. Clinical and laboratory parameters before and after therapy were reviewed and compared. In 92% of cases presenting with repeated vaso-occlusive crisis, VOC disappeared completely during follow up and in 8% we found significant reduction in severity as well as frequency of attacks (p < 0.01). Again in 87%, no further transfusion was required during follow up and in 13%, it further reduced the rate of transfusion (p < 0.01). The median time of response for VOC was 3 months and in transfusion requirement was 5 months. There was also significant reduction in S.Billirubin, S.LDH, disease related complications and rate of hospitalisation with significant improvement in Hb, MCV, and MCH. There is insignificant increase in HbF with median (1.5-2.4)% and in 5 cases >5%. We did not find any remarkable adverse effect of the drug during the study period. Low fixed dose hydroxyurea (10 mg/kg/day) is beneficial in reducing the vaso-occlusive crisis and transfusion requirement in adult HbSS Patients (Arab-Indian Haplotype). It is safe, suitable and is a effective mode of treatment in resource poor setting like India.