We explored the prognostic impact of simple indices that reflect the immunological milieu (neutrophils to lymphocyte ratio [NLR] and systemic immune-inflammation [SII]) in 49 platinum-resistant relapsed ovarian cancer patients. The median progression-free survival (PFS) and overall survival (OS) were 4 and 8 months, respectively. Patients with a lower NLR (≤2.89) had a better PFS (5 vs. 2 months [p = 0.02]) and OS (9 vs. 5 months [p = 0.20]). Factors associated with a worse PFS were NLR > 2.8 (hazard ratio [HR] =2.32, p = 0.02) and SII > 639 (HR =3.70, p = 0.002). SII > 639 independently predicted PFS (HR =4.13, p = 0.03). Future studies should study the validity of inflammatory markers and could consider incorporating it as a biomarker in clinical trials.

Patients with platinum-resistant ovarian cancer (PROC) have limited therapeutic options and poor survival. There is a need for the development of newer therapies. Sodium valproic acid (VPA) is a short-chain fatty acid histone deacetylase (HDAC) inhibitor with antitumor activity in preclinical models of PROC. Synergism with conventional cytotoxic agents like etoposide has been demonstrated. In this prospective, single-arm, open-label, phase 2 study, we included patients ≥ 18 years with histologically or cytologically confirmed PROC and Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-3. Patients received oral VPA 60 mg/kg/day in three divided doses for 3 days (D1-D3), followed by oral etoposide 50 mg once daily for two consecutive weeks (D4-D17). Serum samples were collected to assess peak VPA drug levels. The primary endpoint was the overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. We sought to show an improvement in response rate from 25% (historically with oral etoposide) to 40% with the addition of VPA. 27 patients were enrolled in the study, and 18 [median age: 52 (45-59) years; serous histology:17 (94%); ECOG-PS 2 or 3: 14 (78%)] were evaluable for the response after 4 months. Nine patients were lost from follow-up before achieving the primary endpoint (mainly due to Covid-related lockdown issues). The median number of prior lines of treatment was 2 (1-3). ORR was 0% according to GCIG criteria. The disease was stable in two patients [clinical benefit rate (CBR) of 11%]. The median OS and PFS were 7 months and 2 months, respectively. Grade ≥ 3 adverse events were reported in 6 (33%) patients. The addition of valproic acid to oral etoposide in patients with PROC and poor general condition was not helpful and failed to improve responses compared to those historically achieved with single-agent etoposide. However, further phase 2 randomized controlled trials with larger sample size can be done to confirm the findings.

The blast phase (BP) is challenging to treat and leads to inferior survival in chronic myeloid leukemia (CML). Allogeneic hematopoietic stem cell transplant (AlloSCT) is the only curative option for CML-BP. We are sharing our experience of AlloSCT in seven patients with CML-BP who underwent transplants during the period from January 2017 to December 2019. Three patients each had myeloid-BP, lymphoid-BP, and one patient had mixed phenotypic BP. Donors were matched siblings in four, mismatched siblings in one, and haploidentical in two. All patients received peripheral blood stem cell grafts. The median CD34+ dose was 7.6 (range: 6.6–8.9) × 106 cells/kg. Neutrophil engraftment was observed at a median of 15 (10–20) days and platelet engraftment at 19 days (10–22). At a median follow-up of 24 months, the 2-year leukemia-free survival (LFS) and overall survival (OS) were 43% and 57%, respectively. Transplant-related, non-relapse mortality was observed in three patients. AlloSCT results in promising survival for carefully selected patients of CML-BP, especially with a matched sibling donor.

Background: Patients with platinum-resistant ovarian cancer (PROC) have limited therapeutic options and poor survival. There is a need for the development of newer therapies. Sodium valproic acid (VPA) is a short-chain fatty acid histone deacetylase (HDAC) inhibitor with antitumor activity in preclinical models of PROC. Synergism with conventional cytotoxic agents like etoposide has been demonstrated. Methodology: In this prospective, single-arm, open-label, phase 2 study, we included patients ≥18 years with histologically or cytologically confirmed PROC and Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-3. Patients received oral VPA 60 mg/kg/day in three divided doses for three days (D1-D3), followed by oral etoposide 50 mg once daily for two consecutive weeks (D4-D17). Serum samples were collected to assess peak VPA drug levels. The primary endpoint was the overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. We sought to show an improvement in response rate from 25% (historically with oral etoposide) to 40% with the addition of VPA. Results: 27 patients were enrolled in the study, and 18 [median age: 52 (45-59) years; serous histology:17(94%); ECOG-PS 2 or 3: 14 (78%)] were evaluable for the response after four months. Nine patients were lost from follow-up before achieving the primary endpoint (mainly due to Covid-related lockdown issues). The median number of prior lines of treatment was 2 (1-3). ORR was 0% according to GCIG criteria. The disease was stable in two patients [clinical benefit rate (CBR) of 11%]. The median OS and PFS were seven months and two months, respectively. Grade ≥3 adverse events were reported in 6 (33%) patients. Conclusion: The addition of valproic acid to oral etoposide in patients with PROC and poor general condition was not helpful and failed to improve responses compared to those historically achieved with single-agent etoposide.

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