Background: Measurable/minimal residual disease (MRD) status is suggested as a powerful indicator of clinical-outcome in T-cell lymphoblastic leukemia/lymphoma (T-ALL). Contrary to B-cell ALL, reports on TALL MRD are limited and mostly based on molecular methods, mainly from developed countries. Multicolor flow cytometry (MFC)-based TALL studies are very few. Clinically relevant cutoff levels and ideal time-point for MRD assessment are still inconclusive. In view of lack of TALL MRD data from the developing world, we evaluated the prognostic value of MFC-based post-induction (PI)-MRD assessment in TALL in the context of standard practice. Methods: We included 256 childhood-TALL patients (age < 15 years) treated with a modified-MCP841 protocol, which uses high-dose cytarabine during consolidation, as a part of standard hospital practice. MRD was studied using 10-color 11-antibody MFC with any level of detectable disease being considered positive. Post-induction (PI)-MRD was available in all patients, and post-consolidation (PC) MRD was available mostly in PI-MRD-positive patients (n = 88). Results: Three years cumulative-incidence-of-relapse (3years-CIR) in PI-MRD-positive patients was inferior to negative patients (46.3% vs. 18.4%). The median relapse-free-survival (RFS), event-free-survival (EFS) and overall-survival (OS) with hazard ratio (HR) of PI-MRD-positive patients were 21.4 months vs not reached (p < 0.0001, HR-4.7), 21.6 months vs. not-reached (p = 0.0003, HR-2.01) and 37.3 months vs. not reached (p = 0.026, HR-1.64) respectively. RFS, EFS and OS of patients with PI-MRD<0.01% (n = 17) were as inferior as PI-MRD ≥ 0.01% in comparison Tembhare et al. Post-induction MRD & WBC Count in TALL with MRD-negative patients with HR of 4.7 (p < 0.0001), 2.45 (p = 0.0003), and 2.5 (p = 0.029), respectively. Three-years-CIR of patients with hyperleukocytosis (≥100 × 109/L) was also higher (50.5 vs. 27.6%) with inferior RFS, EFS, and OS. Among PI-MRDpositive patients, 3years-CIR, RFS, EFS, and OS of PC-MRD-positive were also inferior to that of negative patients. On multivariate analysis any-level detectable PI-MRD and hyperleukocytosis remained independently associated with inferior RFS, EFS, and OS. A combination of PI-MRD-positive status and hyperleukocytosis identified the patients with the worst clinical outcomes. Conclusion: Detectable PI-MRD using MFC was found to be the strong predictive factor of inferior clinical outcome in TALL patients. The combination of PI-MRD status and hyperleukocytosis provides the most influential tool for the management of TALL in resource constrained settings from developing world.

Background Many novel therapies are being evaluated for the treatment of Multiple myeloma (MM). The cell‐surface protein B‐cell maturation antigen (BCMA, CD269) has recently emerged as a promising target for CAR‐T cell and monoclonal‐antibody therapies in MM. However, the knowledge of the BCMA expression‐pattern in myeloma patients from the Indian subcontinent is still not available. We present an in‐depth study of BCMA expression‐pattern on abnormal plasma cells (aPC) in Indian MM patients. Methods We studied BM samples from 217 MM patients (211‐new and 6‐relapsed) with a median age of 56 years (range, 30–78 years & M:F‐2.29) and 20 control samples. Expression levels/patterns of CD269 (clone‐19f2) were evaluated in aPCs from MM patients and in normal PCs (nPC) from uninvolved staging bone marrow samples (controls) using multicolor flow cytometry (MFC). Expression‐level of CD269 was determined as a ratio of mean fluorescent intensity (MFI‐R) of CD269 in PCs to that of non‐B‐lymphocytes and expression‐pattern (homogenous/heterogeneous) as coefficient‐of‐variation of immunofluorescence (CVIF). Results Median (range) percentage of CD269‐positive abnormal‐PCs in total PCs was 71.6% (0.49–99.29%). The MFI‐R (median, range) of CD269 was significantly higher in aPCs (4.13, 1.12–26.88) than nPCs (3.33, 1.23–12.87), p < .0001. Median (range) MFI of CD269 at diagnosis and relapse were 2.39 (0.77–9.57) and 2.66 (2.15–3.23) respectively. CD269 levels were similar at diagnosis and relapse, p = .5529. Conclusions We demonstrated that BCMA/CD269 is highly expressed in aPCs from a majority of MM patients, both at diagnosis and relapse. Thus, BCMA is a valuable target for therapy for Indian MM patients.