Assessment of Radiation Doses Delivered to Organs at Risk Among Patients With Early-Stage Favorable Hodgkin Lymphoma Treated With Contemporary Radiation Therapy.

Importance: Response-adapted randomized trials have used positron emission tomography-computed tomography to attempt to identify patients with early-stage favorable Hodgkin lymphoma (ESFHL) who could be treated with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) without radiation therapy (RT). While maximal efficacy is demonstrated with combined modality therapy, RT is often omitted in fear of late adverse effects; however, the application of modern RT could limit these toxic effects. Objective: To determine the radiation doses delivered to organs at risk with modern involved-site RT among patients with ESFHL treated with 20 Gy after 2 cycles of ABVD. Design, Setting, and Participants: This case series included 42 adult patients with ESFHL (according to the German Hodgkin Study Group criteria) who were treated between 2010 and 2019, achieved complete response by positron emission tomography-computed tomography (1-3 on 5-point scale) following 2 cycles of ABVD, and then received consolidative RT. The study was conducted at a single comprehensive cancer center. Exposures: 2 cycles of chemotherapy followed by 20-Gy involved-site RT. Main Outcomes and Measures: The medical records of patients with ESFHL were examined. Organs at risk were contoured, and doses were calculated. Progression-free survival, defined from date of diagnosis to disease progression, relapse, or death, and overall survival were estimated using the Kaplan-Meier method. Results: The cohort comprised 42 patients with ESFHL (median [range] age at diagnosis, 35 [18-74] years; 18 [43%] women; 24 [57%] with stage II disease). At a median follow-up of 44.6 (95% CI, 27.6-61.6) months, the 3-year progression-free survival and overall survival rates were 91.2% (95% CI, 74.9%-97.1%) and 97.0% (95% CI, 80.4%-99.6%), respectively. The mean heart dose was less than 5 Gy (mean, 0.8 Gy; SD, 1.5 Gy; range, 0-4.8 Gy) in all patients. The mean (SD) breast dose for both breasts was 0.1 (0.2) Gy (left breast range, 0-1.0 Gy; right breast range, 0-0.9 Gy). Conclusions and Relevance: In this study, combined modality therapy with 2 cycles of ABVD and 20 Gy for ESFHL was highly effective and avoided excess doses to organs at risk, which may limit long-term toxic effects.

Pilot study using post-transplant cyclophosphamide (PTCy), tacrolimus and mycophenolate GVHD prophylaxis for older patients receiving 10/10 HLA-matched unrelated donor hematopoietic stem cell transplantation.

Allogeneic SCT for older patients remains challenging at least in part due to graft-versus-host disease (GVHD) and higher non-relapse mortality (NRM). We conducted a prospective pilot study primarily for older patients undergoing matched unrelated donor (MUD) SCT using a reduced-intensity (RIC) melphalan-based conditioning and post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis with tacrolimus and mycophenolate mofetil. Twenty-two patients (median age 64, IQR 58, 66) underwent RIC MUD SCT for high-risk hematological malignancies including AML/MDS (73%), CML/MPD (18%), and other (10%). Two (9%) patients had early death; the rest (100%) engrafted. After a median follow-up of 17 months, 11 patients were alive and disease-free with an estimated 2-year progression-free (PFS) and overall (OS) survival of 48%. The cumulative incidences of grades 2-4 and 3-4 acute GVHD (aGVHD) at day + 100 and 2-years were 32 and 4%, and 59 and 24%, respectively. No cases of chronic GVHD (cGVHD) were noted. However, late acute GVHD was observed in 6 (27%) patients. In conclusion, RIC MUD SCT with melphalan-based conditioning and PTCy-based GVHD-based prophylaxis for older patients appears effective in controlling relapse. While cGVHD was not seen and early aGVHD appears controllable, a significant proportion developed late aGVHD responsible for higher NRM seen in these patients.

A randomized phase 2 trial of a preparative regimen of bortezomib, high-dose melphalan, arsenic trioxide, and ascorbic acid.

BACKGROUND: Bortezomib is active for newly diagnosed and relapsed multiple myeloma, and it has synergistic activity with melphalan. The authors of this report conducted a randomized trial to determine the safety and efficacy of adding bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA), and melphalan. METHODS: Among 60 patients who enrolled between October 2006 and September 2007, 58 patients underwent autologous transplantation with a preparative regimen of melphalan 200 mg/m(2) intravenously, AA 1000 mg daily intravenously for 7 days, and ATO 0.25 mg/kg intravenously for 7 days. Patients were randomized to receive no bortezomib (Group 1), bortezomib 1 mg/m(2) × 3 doses (Group 2), and bortezomib 1.5 mg/m(2) × 3 doses (Group 3). Primary endpoints were complete response (CR), grade IV toxicity, and 90-day treatment-related mortality (TRM). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). RESULTS: The median follow-up of all surviving patients was 36 months (range, 20-43 months). The CR rates in Groups 1, 2, and 3 were 20%, 10%, and 10%, respectively. Grade 3 and 4 nonhematologic toxicities and TRM were comparable. The median OS was not reached in the groups, whereas the median PFS in Groups 1, 2, and 3 was 17.8 months, 17.4 months, and 20.7 months, respectively. PFS and OS were significantly shorter in patients who had high-risk cytogenetics (P = .016 and P = .0001, respectively) and relapsed disease (P = .0001 and P = .0001, respectively) regardless of the treatment group. CONCLUSIONS: Adding bortezomib to a preparative regimen of ATO, AA, and high-dose melphalan was safe and well tolerated in patients with multiple myeloma. There was no significant improvement in the CR rate, PFS, or OS in the bortezomib groups.