Treatment challenges and outcomes of older patients with acute myeloid leukemia from India.

Globally, overall survival (OS) of older patients with AML continues to be suboptimal with very little data from India. In a multicenter registry analysis, we evaluated 712 patients with AML older than 55 years. Only 323 (45.3%) underwent further treatment, of which 239 (74%) received HMAs, and 60 (18%) received intensive chemotherapy (IC). CR was documented in 39% of those receiving IC and 42% after HMAs. Overall, 100 (31%) patients died within 60 days of diagnosis, most commonly due to progressive disease (47%) or infections (30%). After a median follow-up of 176 days, 228 (76%) of patients had discontinued treatment. At one year from diagnosis, 211 (65%) patients had died, and the median OS was 186 days (IQR, 137-234). Only 12 (3.7%) patients underwent stem cell transplantation. Survival was significantly lower for those older than 60 years (p < 0.001). Patients who died had a higher median age (p = .027) and baseline WBC counts (p = .006). Our data highlights suboptimal outcomes in older AML patients, which are evident from 55 years of age onwards, making it necessary to evaluate HMA and targeted agent combinations along with novel consolidation strategies to improve survival in this high-risk population.

A Prospective Study to Evaluate the Effect of Therapeutic Drug Monitoring-Based Posaconazole Prophylaxis on Invasive Fungal Infection Rate During Acute Myeloid Leukemia Induction Therapy.

Invasive fungal infections (IFIs) are a significant cause of morbidity and mortality in de-novo acute myeloid leukemia patients receiving induction chemotherapy. Despite using posaconazole, a broad-spectrum antifungal, for IFI prophylaxis, the breakthrough IFI rate is high in the real-world setting. One of the reasons could be frequent suboptimal plasma posaconazole levels. In the present study, we evaluated if therapeutic drug monitoring (TDM) guided posaconazole prophylaxis can reduce the IFI rates in comparison to a historical cohort. We enrolled 90 patients, > / = 16 years of age, without baseline IFIs, planned for remission induction therapy. All patients were started on posaconazole suspension 200 mg TDS and the dose was increased in a stepwise manner if trough levels were found to be suboptimal (< 350 ng/ml for day 2 or < 700 ng/ml subsequently). The TDM based approach resulted in a significant decline in breakthrough IFI rates (18% versus 52%, P < 0.0001) A total of 69 patients (78%) required dose escalation. Thirty-one patients required change in antifungals due to either suboptimal levels, persistent fever, diarrhoea or vomiting. We could not demonstrate an exposure-response relationship but the difference in IFI rates in patients with a median posaconazole level > / = 700 ng/ml (0%) and < 700 ng/ml (21.6%) was clinically meaningful. Posaconazole levels were found to be significantly lower in patients on antacids and prokinetics. The incidence of posaconazole-related grade 3 toxicity was low (2.3%). Thus TDM-based dosing of posaconazole helps reduce breakthrough IFI rate and should be a part of posaconazole prophylaxis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01709-3.

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.