Circulating tumor plasma cells and peripheral blood measurable residual disease assessment in multiple myeloma patients not planned for upfront transplant.

Circulating tumor plasma cells (CTPCs) provide a noninvasive alternative for measuring tumor burden in newly diagnosed multiple myeloma (NDMM). Moreover, measurable residual disease (MRD) assessment in peripheral blood (PBMRD) can provide an ideal alternative to bone marrow MRD, which is limited by its painful nature and technical challenges. However, the clinical significance of PBMRD in NDMM still remains uncertain. Additionally, data on CTPC in NDMM patients not treated with transplant are scarce. We prospectively studied CTPC and PBMRD in 141 NDMM patients using highly sensitive multicolor flow cytometry (HS-MFC). PBMRD was monitored at the end of three cycles (PBMRD1) and six cycles (PBMRD2) of chemotherapy in patients with detectable baseline CTPC. Patients received bortezomib-based triplet therapy and were not planned for an upfront transplant. Among baseline risk factors, CTPC ≥ 0.01% was independently associated with poor progression-free survival (PFS) (hazard ratio [HR] = 2.77; p = 0.0047) and overall survival (OS) (HR = 2.9; p = 0.023) on multivariate analysis. In patients with detectable baseline CTPC, undetectable PBMRD at both subsequent time points was associated with longer PFS (HR = 0.46; p = 0.0037), whereas detectable PBMRD at any time point was associated with short OS (HR = 3.25; p = 0.004). Undetectable combined PBMRD (PBMRD1 and PBMRD2) outperformed the serum-immunofixation-based response. On multivariate analysis, detectable PBMRD at any time point was independently associated with poor PFS (HR = 2.0; p = 0.025) and OS (HR = 3.97; p = 0.013). Thus, our findings showed that CTPC and PBMRD assessment using HS-MFC provides a robust, noninvasive biomarker for NDMM patients not planned for an upfront transplant. Sequential PBMRD monitoring has great potential to improve the impact of the existing risk stratification and response assessment models.

Long-term clinical outcomes of combined modality therapy for advanced-stage Hodgkin lymphoma in the PET era: A retrospective study.

BACKGROUND OBJECTIVES: The role of consolidation radiation therapy (CRT) after complete metabolic response to chemotherapy in advanced-stage (stage III and IV) Hodgkin lymphoma (HL) is controversial. This study was undertaken to assess the clinical outcomes in terms of event free survival, local failure free survival and overall survival in individuals with advanced HL treated with chemotherapy and CRT. METHODS: A retrospective review was conducted to study the long-term clinical outcomes in individuals diagnosed with HL and treated with chemotherapy and CRT from 2012 to 2016 at a tertiary cancer care hospital in India. RESULTS: Data from 203 study participants with advanced-stage HL were analyzed. Positron emission tomography-computed tomography (PET-CT) was done at baseline and after 2 cycles for response assessment. The median age at presentation was 32 yr [interquartile range (IQR): 26-46]. Early metabolic response (after 2 cycles) and delayed metabolic response (after 4 or 6 cycles) were observed in 74.4 and 25.6 per cent of individuals, respectively. With a median follow up of 52 months (IQR: 40-67), the five-year event-free survival (EFS), local failure-free survival (LFFS) and overall survival (OS) were 83.2, 95.1 and 94.6 per cent, respectively. On univariate analysis, extranodal disease was associated with inferior EFS (P=0.043). Haemoglobin <10.5 g/dl (P=0.002) and Hasenclever index >3 (P=0.00047) were associated with poorer OS. Relapses were observed in 28/203 (13.8%) study participants with predominance at central nodal stations. The median time to relapse was 19.4 months (IQR: 13-33). Local relapse alone (at the irradiated site) was observed in 5/28 study participants, systemic (distant) relapse in 14/28 individuals, while both systemic and local relapse was observed in 9/28 participants. Extranodal disease (P=0.05), bulky disease (P=0.005) and haemoglobin concentration ≤10.5 g/dl (P=0.036) were significant predictors for disease relapse. INTERPRETATION CONCLUSIONS: Individuals with advanced-stage HL treated with anthracycline-based chemotherapy (anthracycline-based chemotherapy with doxorubicin, bleomycin, vinblastine and dacarbazine regimen) and CRT had excellent long-term outcomes. As isolated infield failures are uncommon, selective consolidation with conformal RT to high-risk sites improves final disease outcomes.

A Retrospective Cohort Study to Evaluate the Outcomes of HIV-Associated High-Grade B-Cell Non-Hodgkin Lymphoma (NHL) Treated with Dose Adjusted EPOCH (+/-R) Regimen.

High-grade B-cell NHL's are more common in seropositive patients. They are biologically different from their seronegative counterparts. We report our analysis on our cohort of patients who were treated with DA-EPOCH(+/-R). We retrospectively analyzed treatment-naïve HIV-associated High-grade B-cell NHL patients (aged ≥ 18) treated with DA-EPOCH(+/-R) regimen from 2011 to 2015. Descriptive statistics were summarized with median and range; survival outcomes were analyzed with Kaplan-Meier method. The cohort comprised of 40 patients [DLBCL(19), Burkitt's Lymphoma(16), High-grade B-Cell Lymphoma-Unclassifiable(09), and Plasmablastic Lymphoma(01)] and the median CD4 + T cell count was 202/mm3. CNS prophylaxis was administered with intrathecal methotrexate to 90% of patients. With a median follow-up of 72 months, an estimated 5-year OS was 82.5%, and 5-PFS was 77.5%. There were 9 deaths, and 9 patients had progression. At least 4 cycles of chemotherapy were administered to 35 (93%) patients, with 28 (70%) receiving 6 cycles. Grade 3-4 toxicities were seen in 33 (83%) patients- febrile neutropenia (65%) being the most common followed by mucositis (25%) and peripheral neuropathy (13%). There was no difference in survival based on IPI, CD 4 + T cell count, CDI, or duration of HIV. DA-EPOCH(+/-R) is a highly effective regimen in seropositive high-grade B-cell lymphoma, even in the presence of adverse features. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01652-3.

Clinical Utility of Stepwise Bronchoalveolar Lavage Fluid Analysis in Diagnosing and Managing Lung Infiltrates in Leukemia/Lymphoma Patients With Febrile Neutropenia.

PURPOSE: Febrile neutropenia (FN) is a serious complication in hematologic malignancies, and lung infiltrates (LIs) remain a significant concern. An accurate microbiological diagnosis is crucial but difficult to establish. To address this, we analyzed the utility of a standardized method for performing bronchoalveolar lavage (BAL) along with a two-step strategy for the analysis of BAL fluid. PATIENTS AND METHODS: This prospective observational study was conducted at a tertiary cancer center from November 2018 to June 2020. Patients age 15 years and older with confirmed leukemia or lymphomas undergoing chemotherapy, with presence of FN, and LIs observed on imaging were enrolled. RESULTS: Among the 122 enrolled patients, successful BAL was performed in 83.6% of cases. The study used a two-step analysis of BAL fluid, resulting in a diagnostic yield of 74.5%. Furthermore, antimicrobial therapy was modified in 63.9% of patients on the basis of BAL reports, and this population demonstrated a higher response rate (63% v 45%; P = .063). CONCLUSION: Our study demonstrates that a two-step BAL fluid analysis is safe and clinically beneficial to establish an accurate microbiological diagnosis. Given the crucial impact of diagnostic delays on mortality in hematologic malignancy patients with FN, early BAL studies should be performed to enable prompt and specific diagnosis, allowing for appropriate treatment modifications.

Outcomes and prognostic factors of patients with Extranodal NK T cell lymphoma (ENKTL).

The staging, prognostication, and treatment of ENKTL has evolved over the years with better understanding of the disease biology. There is significant heterogeneity in the treatment followed across the world. Literature from India have been few with small number of patients. We studied the outcomes and prognostic factors of patients with ENKTL treated between May 2010 and December 2021 at our center. A total of 78 patients diagnosed with ENKTL were treated at our center. L-asparaginase based chemotherapy was administered in 84% of the patients. Close to 2/3rd patients received SMILE chemotherapy. After a median follow-up of 30 months (18.5-41.4 months), the median relapse free survival and overall survival for the overall population was 45 months (12-118 months) and 45 months (14-118 months) respectively. By multivariate analysis, PINK score of 2-4, non-receipt of RT and non-achievement of CR were associated with poor survival.

Primary central nervous system lymphoma: Comprehension of cell-of-origin subtypes.

Primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL) is an uncommon extranodal lymphoma that accounts for more than 95% of all the CNS lymphomas. Unlike its systemic/nodal counterpart, which is currently subtyped into cell-of origin (COO) subtypes, its feasibility and utility are largely debatable in PCNS-DLBCL. Objectives: To classify PCNS-DLBCL into COO-subtypes based on immunohistochemical algorithms by Hans and Choi and evaluate concordance between the two. A further aim is to investigate the clinicoradiological and histomorphological parameters of the subtypes thus obtained. Materials and Methods: As many as 143 cases of primary CNS lymphoma were evaluated by immunohistochemistry for CD10, BCL6, MUM1, GCET, and FOXP1 and based on which the said 143 cases were further classified into COO subtypes using Hans and Choi algorithms. Results: Mean age was 53.8 years with marginal male preponderance and predominantly centroblastic morphology (75.5%). CD 10 was positive in 8.9% of the cases, BCL6 in 58.6%, MUM1 in 89.9%, GCET in 32.9%, and FOXP1 in 79.5%. As much as 84.9% cases were of non-germinal center B-cell (GCB) subtype and 15.1% cases were of GCB subtype as determined based on Hans algorithm. Furthermore, 90.7% cases were of activated B-cell (ABC) subtype and 9.3% cases were of GCB subtype according to Choi algorithm. A 91.8% concordance was observed between Hans and Choi algorithms. Among the 6 discordant cases, 5 cases were subtyped as GCB by Hans and ABC by Choi and 1 case as ABC by Hans and GCB by Choi. Conclusion: Most of PCNS-DLBCLs are of non-GCB/ABC COO subtype, but inconsistences abound in the utility of IHC algorithms in PCNS-DLBCL COO subtypes.

Navigating the neutropenic abyss with granulocyte transfusions: Retrospective single-center analysis of effectiveness and safety in India.

BACKGROUND: Hemato-oncologic patients receiving intensive chemotherapy may develop severe neutropenia and serious bacterial and/or fungal infections. Granulocyte transfusions (GTs) may be beneficial as a bridging therapy in hemato-oncologic patients with febrile neutropenia. AIM: To evaluate the clinical effectiveness of GTs in hemato-oncologic patients with febrile neutropenia. MATERIALS AND METHODS: This retrospective study evaluated the effectiveness of 150 GTs in 88 hemato-oncologic patients. Donors were mobilized with granulocyte colony-stimulating factors and dexamethasone. Patients' hematological parameters (pre- and post-GT) and safety and effectiveness of GTs were analyzed. RESULTS: The safety and effectiveness of GTs were assessed in the patients with various underlying conditions, including 78% with acute myeloid leukemia. In total, 150 GTs were administered, mostly during the chemotherapy induction phase. The GTs were well-tolerated by the patients, and a significant increment in white blood cell count and absolute neutrophil count (ANC) was noticed in 95% of patients after the transfusion. The granulocyte dose was positively correlated with ANC after the transfusion. The average time to neutrophil recovery from the last day of GT was 6.7 days, and the 30-day survival rate was 77%. The donors were all men, and a significant increase in WBC count was observed post-mobilization. The median granulocyte yield was 2.28 × 1010 /unit. All granulocyte products were crossmatched and irradiated before the transfusion. CONCLUSION: GTs can be a useful adjunctive treatment for febrile neutropenia in hemato-oncologic patients with multidrug-resistant sepsis. However, additional studies are required for confirming their effectiveness and establishing guidelines for their use.

Exposure-Response Relationship of Posaconazole Suspension in Theprophylaxis of Invasive Fungal Infections in Patients with Acute Myeloid Leukemia.

Purpose: Antifungal prophylaxis with posaconazole has demonstrated a reduction in the risk of death due to Invasive fungal infections (IFI)in patients with acute myeloid leukemia (AML) during induction therapy. However, various factors affect the plasma levels of posaconazole and can potentially limit its efficacy. Therapeutic drug monitoring (TDM) can help optimize the dose, but literature is scant from centers with a high IFI burden. This study aimed to evaluate the proportion of de-novo AML patients on induction who could achieve the target level of 700ng/mL with posaconazole prophylaxis,factors that can influence the plasma levels, and the impact of plasma posaconazole levels on incidence of IFI. Methods: Patients with AML on induction therapy with no baseline IFI were enrolled at our tertiary cancer center which has high prevalence of IFI. These patients received posaconazole suspension as prophylaxis. Daily plasma levels were measured from Day 4 till Day 12 of posaconazole prophylaxis. All patients were monitored for the development of IFI. The data on adverse events, concomitant drugs, mucositis, vomiting, and diarrhea were recorded. Results: A total of 411 samples from fifty patients were collected. Only 177 out of 411 samples had levels > 700 ng/mL. The median trough level was 610 ng/mL (range30-3000 ng/mL). The median time to achieve target trough concentration was four days (range 4-12 days) from the start of induction.Thirty-eight (76%) patients achieved target plasma levels by day 12 of induction.The median plasma level on day 12 was 690 ng/mL (range,30-1270) in patients who achieved target levels as compared to 340 (50-560) ng/mL in those who did not. Twenty-six (52%) patients had IFI in our study, and the median time to develop breakthrough IFI was 14 days (range 4-24 days). Median and range of plasma levels were 690 ng/ml (30-2410; n = 22) in those who developed IFI, while 590 ng/mL (50-2300 n = 24) in those who did not. The odds of developing IFI in patients who did not achieve the threshold trough concentration of 700 ng/mL was 7.14 (95% CI; 1.35-37.75, p = 0.0206). Occurrence of vomiting (p = 0.02), diarrhea (p = 0.0008), mucositis (p = 0.003) had adverse impact on achievement of target plasma posaconazole levels. Conclusion: A significant proportion of patients receiving posaconazole prophylaxis fail to achieve target plasma levels which can result in high risk of development of IFI. Occurrence of diarrhea, vomiting and mucositis can adversely affect the achievement target plasma levels.

A phase II study to evaluate the efficacy of low-dose rasburicase (1.5mg) in adolescent and adult acute leukemia and high-grade lymphomas with tumor lysis syndrome.

The FDA recommended dose of rasburicase 0.2 mg/kg/day till the resolution of TLS or up to 5 days, might be in excess and is prohibitively expensive. The quality of evidence supporting low dose rasburicase is limited. The objective is to study the plasma uric acid response rate. This is a single center, non-randomised phase II study. Duration is 10 June 2017 till 30 July 2019. Study setting is at Adult Hematolymphoid Unit, Tata Memorial Center. Participants are patients with acute leukemia and high-grade lymphomas aged >/=18 years, with ECOG PS of 0-3, with either laboratory or clinical TLS. Rasburicase was administered at fixed-dose of 1.5 mg. The subsequent doses (1.5 mg each dose) were administered only if plasma UA levels did not decline by >50% on day 2, at the physician's discretion. We demonstrate that a low-dose rasburicase strategy leads to rapid and sustained reductions of uric acid in about 52% patients.

Frequency of HLA alleles and KIR Ligands in Acute Myeloid Leukemia in Indian Cohort.

Relationship between various combinations of KIR ligands and HLA alleles have been studied in several diseases. The aim of this retrospective study was to estimate the frequency of HLA alleles and KIR ligands among acute myeloid leukemia patients and healthy controls in order to examine the possible association of HLA alleles and KIR ligands with AML. A total of 439 acute myeloid leukemia patients and 1317 unrelated, healthy ethnic Indian controls were included in the study. HLA typing was performed using PCR-SSP. KIR ligands were assigned by using the KIR ligand Calculator. The frequency of HLA alleles and KIR ligands in patients was then compared with the controls. As compared to controls, frequencies of HLA-A*03 and HLA-B*35 were increased in AML patients, whereas, that of HLA-C*03 was decreased. Frequencies of HLA-A*03 and HLA-C*15 were increased in male patients, however, no significant difference was observed in female patients as compared to controls. In the pediatric group, the frequencies of HLA-A*01 was decreased and that of HLA-A*03 and HLA-B*18 were increased, whereas, frequencies of HLA-B*13 was decreased and that of HLA-B*27 was increased in the adult patients. In the haplotype analysis, the frequency of HLA-A*24/B*35/DRB1*15 was increased in overall patients. In adult group, the frequency of HLA-A*01/B*44/DRB1*07 was increased in patients than in controls. No significant association was observed between KIR ligands and susceptibility/ protection to AML. Our results indicate that certain HLA alleles and haplotypes have presumptive positive or negative role in conferring protection/susceptibility to AML. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01550-0.

Demographics, Pattern of Care & Outcomes of Primary CNS Lymphoma- Experience from a Tertiary Care Cancer Center in India.

Primary CNS lymphoma (PCNSL) is a rare subtype of non-Hodgkin lymphoma with the worst outcomes amongst all extranodal lymphomas. There is a scarcity of data on real-world outcomes of primary CNS lymphoma (PCNSL) owing to the rarity of the disease. This study analyzed the demographic patterns, risk stratification, treatment regimens used, & outcomes of patients treated at Tata Memorial Center Mumbai, India. This is a retrospective analysis of newly diagnosed primary CNS lymphoma patients treated at our centre over seven years from January 2013 to December 2019. A total of 142 patients with PCNSL were diagnosed during this period. Thirty (21.1%) patients were deemed ineligible for any systemic or local therapies,ten patients were referred to other hospitals, two patients had relapsed disease, and one was excluded because age less than 18 years. Finally 99 patients were included in the final analysis. Among these 99 patients,72 patients (72.7%) were < 60 years,70 (70.7%) patients had Eastern cooperative oncology group (ECOG) performance status (PS) less than equal to 2. DLBCL was the most common histology (86.4%) while rests were high grade B cell NHL NOS (11.4%),Burkitt's Lymphoma(1%),Peripheral T-cell Lymphoma NOS (1.2%). Only one of 99 patients was positive for HIV serology. Multiple intracranial lesions were found in 59.5%. Surgical resection was performed in 28.4% of patients. Out of 63 patients in whom the International extranodal lymphoma study group (IELSG) score is available, 34(54%) were IELSG high-risk groups. As per Memorial Sloan Kettering Cancer Center (MSKCC) risk grouping, patients were almost equally distributed in all the risk groups, with 32(32.3%) patients in risk group 1 (age < 50 years), 36(36.4%) patients in risk group 2 (age > 50 years, KPS > = 70), and 31(31.3%) patients in risk group 3 age > 50 years, KPS < 70). First-line treatment with high dose methotrexate (HD-MTX) based regimens was administered to 92 (92.9%) patients, and 72.8% of these patients received rituximab. Of these 92 patients, 59 (64.1%) patients could complete induction, and 52 patients received consolidation. Thirty-one patients received high dose cytarabine based chemo consolidation, one patient underwent high dose chemotherapy followed by autologous stem cell transplantation (ACST), and 19 patients received whole-brain radiotherapy (WBRT) and 1 patient received temozolomide as consolidation regimen. Thus only 52 patients completed the entire course of induction with consolidation therapy. The response to treatment was assessed using International PCNSL Collaborative Group Criteria. Post completion of consolidation, 49(94.2%) patients had a complete response. With a median follow-up duration of 39.2 months, the median progression-free survival (PFS) and the median overall survival (OS) of the patients taken into the analysis (N = 99) were 21 and 37 months respectively. On multivariate analysis, age < 60 yrs, > = 5 HD-MTX cycles received & the use of rituximab predicted better OS.Outcomes of patients with PCNSL treated with HD-MTX based therapy are comparable to reported literature however a large proportion of patients do not undergo required treatment despite the curable nature of disease. Supplementary Information: The online version supplementary material available at 10.1007/s12288-022-01557-7.

Phase II trial of a novel chemotherapy regimen CVEP (cyclophosphamide, vinblastine, etoposide and prednisolone) for acquired immunodeficiency syndrome (AIDS)-associated lymphomas.

Management of acquired immunodeficiency syndrome (AIDS)-related diffuse large B-cell (DLBCL) and plasmablastic lymphomas (PBL) poses significant challenges. The evidence supports use of dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin) with or without rituximab as first-line therapy. The need for central venous access, growth factors and significant toxicities limits its use in resource-constrained settings. To address these challenges, we have developed a novel regimen, CVEP (cyclophosphamide, vinblastine, etoposide, and prednisolone) based on the pharmacodynamic principles of dose-adjusted EPOCH. This single-centre phase II study evaluated the efficacy and safety of CVEP regimen in patients with de novo systemic AIDS-related DLBCL and PBL. The primary objective was complete response (CR) rates as assessed by positron emission tomography-computed tomography. The secondary objectives were incidence of Grade 3/4 toxicities, toxicities requiring hospitalisation, and disease-free survival. From May 2011 to February 2017, 42 patients were enrolled. At the end of therapy the CR rates were 69% (29/42) in the intention-to-treat population and 80.5% (29/36) in evaluable patients. At a median follow-up of 69 months, the 5-year disease-free survival was 65.3%. Out of 217 cycles administered, febrile neutropenia occurred in 19.3% and hospitalisation was required in 18.3% of cycles. There were two treatment-related deaths. The CVEP regimen is an active and safe regimen for AIDS-related DLBCL and PBL.

Expression levels and patterns of B-cell maturation antigen in newly diagnosed and relapsed multiple myeloma patients from Indian subcontinent.

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.

Feasibility of Delivering High-Dose Methotrexate in Adolescent and Adult All Patients: A Retrospective Study.

Introduction HD-MTX is a key drug in the treatment protocols for ALL. The regimen needs to be administered with appropriate supportive measures and serum methotrexate level monitoring. A limited testing strategy is relevant in resource constraint settings since it allows a shorter duration of hospitalization. We report our experience with this strategy and its impact on the patient safety outcomes. Methods This is a retrospective study of all patients ≥ 15 years of age with newly diagnosed ALL or Lymphoblastic lymphoma (LBL) who were administered HDMTX (part of BFM-90 ALL protocol) at our institute between March 2013 to November 2013.The medical records were reviewed for clinical characteristics, disease-related details, HDMTX dose and cycles administered, leucovorin rescue and toxicities. Results A total of 423 cycles of HD-MTX were administered to 106 patients during the study period. The median duration for completion of all 4 cycles of HDMTX was 53 (IQR 49-60) days. The grade 3 or higher toxicities were anemia in 9.6%, neutropenia 19.4%, febrile neutropenia 5.7%, thrombocytopenia 4.4% and mucositis in 0.7%. There was statistically significant correlation between the levels at 42 h (≤ 1 mmol/L vs > 1 mmol/L) and toxicity- anemia, FN and mucositis observed more in the late clearance group. With limited sampling strategy whereby if the 42- hour level MTX level are < 1 mmol/L, 57% of patients could be discharged early. Conclusion HD-MTX can be safely administered to adolescent and adult ALL patients. A limited methotrexate level monitoring is a safe strategy that can optimize the resources better.

"Diffuse Large B-Cell Lymphoma in the Elderly: Real-World Outcomes From a Developing Country".

BACKGROUND: Treatment of Diffuse Large B-Cell Lymphoma (DLBCL) in the elderly aims to achieve disease remission while minimizing treatment-related toxicities. The use of anthracycline in the elderly is associated with increased risk of cardiotoxicity and myelosuppression. Non-anthracycline-based regimens have commonly been used in patients with cardiac contraindications or anticipated severe toxicities to anthracyclines. METHODS: We retrospectively analyzed the treatment outcomes of patients, aged 60 years and above, newly diagnosed with DLBCL at our center. Of a total of 218 patients, 71 patients received the R-CHOP regimen (Rituximab, Cyclophosphamide, Doxorubicin, Vincristine and Prednisolone) and 137 received R-CE (Etoposide) OP chemotherapy. The decision to substitute etoposide for doxorubicin was based on physician's discretion depending on the performance status, cardiac comorbidities and frailty as well as available resources for supportive care. RESULTS: The 2-year progression-free survival (PFS) rate in the R-CHOP group was higher than that in the R-CEOP group (79.1% vs 49.6%, P-value < .001) and this superiority of R-CHOP was seen in both early and advanced disease. The incidence of febrile neutropenia and grade III/IV hematological toxicities was significantly higher in the R-CHOP group in the age group of 60 to 65 years'. ECOG PS at presentation, NCCN-IPI and the chemotherapy regimen were found to be significant factors for 2-year PFS rate by multivariate analysis. CONCLUSION: Anthracycline-based regimen should be used in elderly fit patients without absolute cardiac contraindications wherever feasible with adequate access to supportive care.

The current treatment approach to adolescents and young adults with acute lymphoblastic leukemia (AYA-ALL): challenges and considerations.

INTRODUCTION: AYA-ALL differs from pediatric ALL in terms of clinical, biological, psychosocial factors and access to care and has an inferior outcome. It is now being recognized that pediatric-inspired protocols are superior to adult protocols for this cohort, but given the lack of randomized trials, several questions remain unanswered. AREAS COVERED: In this review, we discuss how AYA-ALL is different from the pediatric ALL population, compare AYA-ALL with ALL in middle and older age adults, review the studies that have enrolled the AYA cohort, summarize risk-stratified and response-adapted approaches, describe the biological subtypes, and review the novel agents/approaches under evaluation. EXPERT OPINION: AYA-ALL is a complex and challenging disease that needs multidisciplinary and focused care. Well-designed clinical trials that focus on this cohort are needed to further improve the outcomes.

Outcomes of COVID-19 and risk factors in patients with cancer.

Patients with cancer are at higher risk for adverse coronavirus disease 2019 (COVID-19) outcomes. Here, we studied 1,253 patients with cancer, who were diagnosed with severe acute respiratory syndrome coronavirus 2 at a tertiary referral cancer center in India. Most patients had mild disease; in our settings, recent cancer therapies did not impact COVID-19 outcomes. Advancing age, smoking history, concurrent comorbidities and palliative intent of treatment were independently associated with severe COVID-19 or death. Thus, our study provides useful insights into cancer management during the COVID-19 pandemic.

Critical Role of Flow Cytometric Immunophenotyping in the Diagnosis, Subtyping, and Staging of T-Cell/NK-Cell Non-Hodgkin's Lymphoma in Real-World Practice: A Study of 232 Cases From a Tertiary Cancer Center in India.

Background: T-cell/NK-cell non-Hodgkin's lymphoma (T/NK-NHL) is an uncommon heterogeneous group of diseases. The current classification of T/NK-NHL is mainly based on histopathology and immunohistochemistry. In practice, however, the lack of unique histopathological patterns, overlapping cytomorphology, immunophenotypic complexity, inadequate panels, and diverse clinical presentations pose a great challenge. Flow cytometric immunophenotyping (FCI) is a gold standard for the diagnosis, subtyping, and monitoring of many hematological neoplasms. However, studies emphasizing the role of FCI in the diagnosis and staging of T/NK-NHL in real-world practice are scarce. Methods: We included T-cell non-Hodgkin's lymphoma (T-NHL) patients evaluated for the diagnosis and/or staging of T/NK-NHL using FCI between 2014 and 2020. We studied the utility of FCI in the diagnosis and subtyping of T/NK-NHL and correlated the FCI findings with the results of histopathology/immunohistochemistry. For correlation purposes, patients were categorized under definitive diagnosis and subtyping, inadequate subtyping, inadequate diagnosis, and misdiagnosis based on the findings of each technique. Results: A total of 232 patients were diagnosed with T/NK-NHL. FCI findings provided definitive diagnoses in 198 patients and subtyping in 187/198 (95.45%) patients. The correlation between FCI and histopathological/immunohistochemistry results (n = 150) demonstrated an agreement on the diagnosis and subtyping in 69/150 (46%) patients. Of the remaining cases, the diagnosis and subtyping were inadequate in 64/150 (42.7%), and 14/150 (9.33%) were misdiagnosed on histopathology/immunohistochemistry results. FCI provided definitive diagnosis and subtyping in 51/64 (79.7%) patients. Among these, 13 patients diagnosed with peripheral T-cell lymphoma not-otherwise-specified were reclassified (angioimmunoblastic T-cell lymphoma (AITL)-11 and prolymphocytic leukemia-2) on FCI. It corrected the diagnosis in 14 patients that were misdiagnosed (6 B-cell NHL (B-NHL), 3 Hodgkin's lymphoma, 1 acute leukemia, and 1 subcutaneous panniculitis-like T-cell lymphoma) and misclassified (3 T-NHL) on histopathological results. AITL was the commonest T-NHL misclassified on histopathological results. FCI also confirmed the definite involvement in 7/83 (8.4%) and 27/83 (32.5%) bone marrow (BM) samples reported as suspicious and uninvolved, respectively, on histopathological evaluation. Conclusion: AITL was the most frequently diagnosed T/NK-NHL in this study. FCI provided a distinct advantage in detecting BM involvement by T/NK-NHL, especially in patients with low-level involvement. Overall, our study concluded that FCI plays a critical role in the diagnosis, subtyping, and staging of T/NK-NHL in real-world practice.