We hypothesized that transplacental leukocyte trafficking during pregnancy, which induces long-term, stable, reciprocal microchimerism in mother and child, might influence outcome of patients with acute leukemia given parental donor haploidentical hematopoietic stem cell transplantation (HSCT). We analyzed the outcome of 118 patients who received transplants for acute leukemia in 2 centers. Patients received highly T celldepleted haploidentical grafts after myeloablative conditioning. Five-year event-free survival was better in patients who received transplants from the mother than from the father (50.6% ؎ 7.6% vs 11.1% ؎ 4.2%; P < .001). Better survival was the result of both reduced incidence of relapse and transplantation-related mortality. The protective effect was seen in both female and male recipients, in both lymphoid and myeloid diseases; it was more evident in patients receiving transplants in remission than in chemotherapy-resistant relapse. Incidences of rejection and acute graft-versus-host disease were not significantly influenced. Multivariate analysis confirmed donor sex in parental donor transplantation as an independent prognostic factor for survival (hazard ratio, father vs mother ؍ 2.36; P ؍ .003). In contrast, in a control cohort of patients who received transplants from haploidentical siblings, donor sex had no influence on outcome. Although obtained in a retrospective analysis, these data suggest that the mother of the patient should be preferred as donor for haploidentical HSCT.
Background. The event-free survival for pediatric leukemia in low-income Countries is much lower than in high-income countries. Late diagnosis, which is regarded as a contributing factor, may be due to “parental” or “medical” delay. Procedures. The present study analyses determinants of lag time from first symptoms to diagnosis of leukemia, comparing pediatric (0–16 years old) patients in two referral centers, one in Nicaragua and one in Italy. An observational retrospective study was conducted to assess factors influencing the time to diagnosis. Results. 81 charts of children diagnosed with acute myeloid leukemia or lymphoblastic leukemia were analyzed from each centre. Median lag time to diagnosis was higher in Nicaragua than in Italy (29 versus 14 days, P < 0.001) and it was mainly due to “physician delay” (16.5 versus 7 days, P < 0.001), whereas “patient delay” from symptoms to first medical assessment was similar in the two centers (7 versus 5 days, P = 0.27). Moreover, median lag time from symptoms to diagnosis was decreased in Nicaraguan districts were a specific training program upon childhood oncological diseases was carried out (20.5 versus 40 days, P = 0.0019). Conclusions. Our study shows that delay in diagnosis of childhood leukemia is mainly associated with “physician delay” and it may be overcome by programs of continuous medical education.
Data from 423 human epidermal growth factor receptor 2‐negative (HER2−), hormone receptor‐positive (HR+) advanced breast cancer (aBC) patients treated with palbociclib and endocrine therapy (ET) were provided by 35 Italian cancer centers and analyzed for treatment outcomes. Overall, 158 patients were treated in first line and 265 in second/later lines. We observed 19 complete responses and 112 partial responses. The overall response rate (ORR) was 31% (95% confidence interval [CI], 26.6–35.4) and clinical benefit was 52.7% (95% CI, 48–57.5). ORR was negatively affected by prior exposure to everolimus/exemestane (
p = 0.002) and favorably influenced by early line‐treatment (
p < 0.0001). At 6 months, median progression‐free survival was 12 months (95% CI, 8–16) and median overall survival was 24 months (95% CI, 17–30). More favorable outcomes were associated with palbociclib in early lines, no visceral metastases and no prior everolimus/exemestane. The main toxicity reported was neutropenia. Our results provide further support to the use of palbociclib with ET in HER2−, HR+ aBC. Differences in outcomes across patients subsets remain largely unexplained.
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