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The use of pediatrics-inspired protocols in adolescent and young adult (AYA) acute lymphoblastic leukemia (ALL) results in superior survival compared with the adult protocols. Pediatrics-inspired protocols carry an increased risk of toxicity and treatment-related mortality in low resource settings, which can offset the potential benefits. We studied the outcomes and prognostic factors in the treatment of AYA ALL with a pediatrics-inspired regimen. We retrieved data regarding demographics, investigations, treatment details, and toxicities from the electronic medical records of patients diagnosed with ALL in the 15- to 25-year-old age group who were initiated on a modified Berlin-Frankfurt-Münster 90 (BFM-90) protocol between January 2013 and December 2016 at the Tata Memorial Centre. A total of 349 patients in the 15- to 25-year-old age group were treated with a modified BFM-90 protocol. The use of this pediatrics-inspired protocol resulted in a 3-year event-free survival (EFS) and overall survival (OS) of 59.4% and 61.8%, respectively. Only 15 patients underwent an allogeneic stem cell transplant. Minimal residual disease (MRD) persistence postinduction emerged as the only factor predictive of poor outcomes. A modified BFM-90 protocol is an effective and safe regimen for AYA ALL with an OS and EFS comparable to the published literature.

Introduction Many new markers are being evaluated to increase the sensitivity and applicability of multicolor flow cytometry (MFC)‐based measurable residual disease (MRD) monitoring. However, most of the studies are limited to childhood B‐cell lymphoblastic leukemia/lymphoma (B‐ALL), and reports in adult B‐ALL are extremely scarce and limited to small cohorts. We studied the expression of CD304/neuropilin‐1 in a large cohort of adult B‐ALL patients and evaluated its practical utility in MFC‐based MRD analysis. Methods CD304 was studied in blasts from adult B‐ALL patients and normal precursor B cells (NPBC) from non‐B‐ALL bone marrow samples using MFC. CD304 expression intensity and pattern were studied with normalized‐mean fluorescent intensity (nMFI) and coefficient of variation of immunofluorescence (CVIF), respectively. MFC‐based MRD was performed at end of induction (EOI; day‐35), end of consolidation (EOC; day 78‐80), and subsequent follow‐up (SFU) time points. Results CD304 was positive in 120/214(56.07%) and was significantly associated with BCR‐ABL1 fusion (P = .001). EOI‐MRD and EOC‐MRD were positive in 129/214(60.3%) and 50/81(61.72%), respectively. CD304 was positive in a significant percentage of EOI (48%, 62/129) and EOC (52%, 26/50) MRD‐positive B‐ALL samples. Its expression was retained, lost, and gained in 73.7%, 26.3%, and 11.3% of EOI‐MRD and 85.7%, 14.3%, and none of EOC‐MRD samples, respectively. Low‐level MRD (<0.01%) was detectable in 34 of all (EOI + EOC + SFU = 189) MRD‐positive samples, and CD304 was found useful in 50% of these samples. Conclusion CD304 is commonly expressed in adult B‐ALL and clearly distinguish B‐ALL blasts from normal precursor B cells. It is a stable MRD marker and distinctly useful in the detection of MFC‐based MRD monitoring, especially in high‐sensitivity MRD assay.

The expression of CD20 in precursor B-cell ALL is associated with poor outcomes. The addition of rituximab to intensive chemotherapy in CD-20 positive ALL has led to improved outcomes in several studies. However, there is no clear evidence regarding the optimal number of doses and its benefit without an allogeneic stem cell transplant. Achieving measurable residual disease (MRD) negative status post-induction would reduce the requirement for a transplant. Novel approaches are needed to induce a higher proportion of MRD negative complete responses in patients with high-risk ALL. Given bortezomib's activity in relapsed ALL and its synergism with rituximab in B-cell lymphomas, the addition of bortezomib to rituximab and chemotherapy may provide an incremental benefit in CD20-positive-precursor B-cell ALL. We conducted a phase II study to test the activity of bortezomib and rituximab in combination with a pediatric-inspired regimen during induction therapy in newly diagnosed adolescents and adults (&gt;14 years of age) with CD20-positive, Philadelphia (Ph)-negative precursor B- ALL, with bone marrow MRD negativity at the end of induction (EOI) as the primary endpoint. From December 2017 through August 2019, a total of 35 patients were enrolled. EOI-MRD-negative status was achieved in 70.99% of patients, as opposed to 51.7% in the historical cohort treated with chemotherapy alone. MRD negative rates improved to 87.5% post-consolidation. At a median follow-up of 21 months, the event-free survival and overall survival were 78.8% [95% CI - 66%- 94%] and 78.7% [95% CI - 65.8%- 94%], respectively. There was no significant increase in toxicity with bortezomib and rituximab compared to the historical cohort. The incidence of neuropathy was 26% (all less than grade 3). The combination of bortezomib, rituximab, and a pediatric-inspired ALL regimen is active and well-tolerated in de-novo CD20-positive Ph-negative precursor B-ALL. This trial is registered with the Clinical Trials Registry-India, CTRI/2017/04/008393.