Second Neoplasms in Italian Patients with Hairy Cell Leukemia after Treatment with Cladribine: A Multicenter Investigation and Literature Review.

Concern has emerged about the prevalence of second cancers among patients with hairy cell leukemia (HCL) treated with purine analogs. We investigated 513 patients with HCL treated with cladribine over the last 30 years at 18 Italian centers and calculated their standardized incidence ratios (SIRs). We identified 24 patients with a second cancer diagnosed at a median time from treatment with cladribine of 59.9 months (range: 9.2-169.7 months). All patients with solid neoplasms presented with a limited-stage disease, except four cases of locally advanced cancer; multiple myeloma patients had a smoldering disease, while lymphoma patients had stage Ie and stage IV diseases. Response to therapy was complete in 19 cases; 1 patient is still receiving treatment for a relapsing bladder disease, while 2 patients progressed during treatment and died. These two patients died from unrelated causes: one from infection and one due to surgery complications. The median OS from HCL was 98.5 months (range: 38.4-409.2 months), while the median OS from second cancer was 27.6 months (range: 1-117.8 months). The SIR was 0.86 (95% CI: 0.54-1.30) for males and 1.13 (95% CI: 0.36-2.73) for females: no statistically significant differences were highlighted. We were not able to demonstrate an excess of second cancer or a significant association with the specific studied neoplasm.

Anti-PD1 Consolidation in Patients with Hodgkin Lymphoma at High Risk of Relapse after Autologous Stem Cell Transplantation: A Multicenter Real-Life Study.

(1) Background: Consolidation therapy is an emerging strategy for patients with relapsed/refractory (RR) Hodgkin Lymphoma (HL) at high risk of failing salvage autologous stem cell transplantation (ASCT). (2) Objectives: To assess the safety and effectiveness of PD1-blockade consolidation for these high-risk patients. (3) Design: Multi-center retrospective analysis. (4) Methods: We identified 26 patients given anti-PD1 consolidation, from June 2016 to May 2020. (5) Results: Patients displayed the following risk factors: refractory disease (69%), relapse < 12 months from upfront therapy (15%), ≥2 lines of salvage therapy (73%), extranodal disease (65%). Nineteen patients (73%) had ≥3 of these factors. In addition, 16 patients (61%) also displayed PET-positive (Deauville ≥ 4) disease before ASCT. Treatment-related adverse events (TRAEs), never graded > 3, occurred in 12 patients (46.15%) and mainly included skin rashes (41.7%), transaminitis (33.3%), and thyroid hypofunction (25%). Patients completed a median of 13 courses (range 6−30). At a median follow-up of 25.8 months post-ASCT, the median progression-free (PFS) was 42.6 months, with a 2-year PFS and overall survival rates of 79% and 87%, respectively. (6) Conclusions: Post-ASCT consolidation with anti-PD1 is feasible and effective. Further studies are warranted to define the optimal treatment length and patients' subsets more likely to benefit from this approach.

Extramedullary Involvement in Acute Myeloid Leukemia. A Single Center Ten Years' Experience.

The incidence, risk factors, and prognostic significance of extramedullary involvement (EMI) in adult patients with acute myeloid leukemia (AML) have not been established yet. This study analyzed clinical and biological characteristics, the impact on prognosis, and the cumulative incidence of EMI in a monocentric retrospective series. All adult patients diagnosed with AML observed in our institution between January 2010 and December 2017 were included in the analysis. Overall, 346 AMLs were analyzed. The incidence of EMI was 11% (38 patients). The involved sites were: skin (66%), central nervous system (CNS) (23%), pleura (7%), lymph nodes (5%), peritoneum (2%), spleen (2%), pancreas (2%), breasts (2%) and bones (2%). Most patients (91%) had only one EMI site, while 9% had multiple sites affected at the same time. Twenty-four (63%) patients showed signs of EMI at presentation, while extramedullary relapse occurred in 10 patients (26%); 4 patients had EMI both at presentation and relapse. EMI had a significantly higher frequency in patients with monocytic and myelo-monocytic leukemia subtypes (p<0,0001), CD117-negative (p=0,03) at flow cytometry analysis, MLL rearrangements (p=0.001), trisomy 8 (p=0,02). An analysis regarding treatment, overall survival (OS), and disease-free survival (DFS) was performed only on the 28 patients who experienced EMI at the onset of their disease; one EMI patient receiving best supportive care was excluded from OS analysis. The other 27 patients were treated with: conventional chemotherapy (21 patients), hypomethylating agents (5 patients), and low dose cytarabine (1 patient); 8 patients only (28.5%) received an allogeneic stem cell transplantation (allo-HSCT). After induction therapy, complete remission (CR) rate was 22%, with a median DFS of 7.4 months. The median OS of all 27 EMI patients was 11.6 months (range 2-79); this resulted significantly longer for the 8 EMI patients who undergone allo-HSCT than those (19 patients) who did not receive this procedure (16.7 vs. 8.2 months respectively, p=0.02). Univariate and multivariate analyses showed that undergoing allo-HSCT and achieving CR were the main positive prognostic factors for our population's survival (p<0,0001). This study confirms the poor prognosis for EMI patients. Allo-HSCT, applicable however only in some cases, seems to have a crucial role in these patients' therapeutic approach, being associated with a better prognosis.

Therapy-related myeloid neoplasms: clinical perspectives.

Therapy-related myeloid neoplasms (t-MNs) are a complication of cytotoxic treatment for primary tumors and autoimmune diseases. t-MNs result from a complex interaction between individual predisposition and exposition to toxic agents. Some different biological and clinical characteristics can be recognized according to the type of anticancer drug. Compared to de novo myeloid neoplasms, prognosis of t-MN is dismal. Age and karyotype are the most important prognostic factors for t-MN, which should be treated with frontline chemotherapy treatments that are appropriate for patients with myelodysplastic syndrome (MDS) and de novo acute myeloid leukemia (AML) with similar disease characteristics. Allogeneic stem cell transplantation should be considered particularly for unfavorable karyotypes and younger patients with aggressive disease.