Damiano Rondelli’s research while affiliated with University of Illinois Chicago and other places

Hematopoietic cell transplantation is a complex procedure that often places significant emotional, financial, and social stress on patients, their families, and caregivers. The process is demanding, requiring extended hospital stays, frequent appointments, and ongoing posttransplant care. These challenges are compounded by uncertainty surrounding the outcome as well as financial burden. In this review, we underscore the importance of establishing comprehensive support systems for patients, their families, and caregivers throughout this journey. Providing adequate education and counseling with resources can play a vital role in minimizing the impact on patients and their families.

A total of 6767 first hematopoietic cell transplants (HCT), 4121 autologous (61%) and 2646 allogeneic (39%), were reported by 166 teams from 12 Latin American countries that answered the 2022 LABMT/WBMT activity survey. The transplant rate (TR) for Latin America in 2022 was 103 HCT/10 million inhabitants with a wide variation between the different countries. The main indication for allogeneic (allo)-HCT was acute lymphoblastic leukaemia (41%) for the pediatric population and acute myeloid leukemia (32%) for adults. The main indication for autologous (auto)-HCT was neuroblastoma (33%) in children and plasma cell disorders (57%) in adults. In alloHCT, the most used hematopoietic cell source was the bone marrow (54%) in pediatric while peripheral blood stem cells (PBSC) (87%) was in adults. PBSC was the source of choice for autoHCT in both ages. The main trends observed in the period 2019-2022 was a decrease in the number of procedures in 2020 in association with the start of the COVID-19 pandemic, resuming growth in the following years. AlloHCT had a greater growth compared to autoHCT, and it was mainly driven by the utilization of haploidentical related donors, which became the main source from 2020 onwards.

Purpose Overuse of opioids has been associated with a significant public health crisis, yet remain critical as adjunctive treatment in multiple myeloma (MM). Questions remain about the balance between the benefits to risks of ongoing opioid use, especially when the patient’s myeloma is in remission. This retrospective review focuses on the association of chronic opioid use (COU) in a patient population predominantly people of color. Methods A cohort of 174 MM patients who received autologous stem cell transplant (ASCT) at an urban medical center were studied. Results Baseline COU was observed in 52.9% of patients. COU rates and average morphine milligram equivalents (MME) per day were similar in those with and without bone disease. Previous illicit drug use was associated with a higher baseline COU. 142 (81.6%) patients received opioids during ASCT admission, while 105 (60.3%) were discharged on opioids and 72 (41.4%) met criteria for COU at 6 months. Opioid use at hospital discharge was associated with a higher 6-month COU (p = 0.008). COU at 6 months was independently associated with worse overall survival (p = 0.006). Conclusion We describe high rates of baseline COU in MM unrelated to bone disease. A number of patients started opioids during ASCT and were still taking them at 6-month follow-up visit. We demonstrate a negative association of 6-month COU on OS but not on PFS suggesting that opioid-related morbidity may play a role. These data highlight the need to test causality of opioid use on survival while simultaneously improving the management of pain in MM.

Background: Exagamglogene autotemcel (exa-cel) is a non-viral cell therapy that reactivates fetal hemoglobin (HbF) via ex vivo CRISPR-Cas9 editing of autologous CD34+ hematopoietic stem and progenitor cells at the erythroid-specific enhancer region of BCL11A. Exa-cel is approved as a one-time treatment for patients aged ≥12 years with severe sickle cell disease (SCD). We report long-term efficacy and safety for participants with SCD in the ongoing phase 3 CLIMB SCD-121 and CLIMB-131 studies. Methods: CLIMB SCD-121 is a 2-year, phase 3 study of a single-infusion of exa-cel in participants aged 12 through 35 years with SCD and a history of ≥2 vaso-occlusive crises (VOCs)/year for 2 years before screening. Enrollment and dosing are complete; the study is ongoing. The primary efficacy endpoint is the proportion of participants free of severe VOCs for ≥12 consecutive months (VF12); the key secondary efficacy endpoint is the proportion of participants free from inpatient hospitalization for severe VOCs for ≥12 consecutive months (HF12). Evaluation of VF12 and HF12 began 60 days after the last red blood cell (RBC) transfusion for post-transplant support or SCD management. Participants evaluable for the primary and key secondary endpoints had ≥16 months of follow-up after exa-cel infusion. Participants who complete CLIMB-121 may enroll in the 13-year long-term extension study, CLIMB-131, where they will be followed for a total of 15 years. Results: As of May 2024, a total of 46 participants (mean age of all participants: 21.4 years, range: 12, 34; mean age of adolescents 12 through 18 years of age [N=12]: 14.5 years, range: 12, 17) with mean 4.2 VOCs/year at baseline received exa-cel after myeloablative busulfan conditioning and had a median follow-up of 29.9 months (range: 8.9, 58.9). Of these participants, 31 completed 2 years of follow-up in CLIMB SCD-121 and transitioned to CLIMB-131. After exa-cel infusion, all 46 participants engrafted neutrophils and platelets at a median of 27 days (range: 15, 40) and 34.5 days (range: 23, 126), respectively. Of the 46 participants, 40 were evaluable for the primary and key secondary endpoints of which 36 (90.0%) achieved VF12 (95% CI: 76.3%, 97.2%) and 38 (95.0%) achieved HF12 (95% CI: 83.1%, 99.4%). In participants achieving VF12, mean VOC-free duration was 29.3 months (range: 14.0, 56.3). All participants, including those who did not achieve VF12, maintained increased levels of hemoglobin (Hb) and HbF and stable allelic editing, supporting that the effects from exa-cel are durable over time in all patients. For all participants, mean total Hb was 11.9 g/dL from Month 3 and was maintained at normal or near normal levels of ≥12 g/dL from Month 6 onward; mean HbF was 37.4% at Month 3 and generally ≥40% from Month 6 onward with pancellular distribution (≥95% RBCs express HbF). Proportion of edited BCL11A alleles was stable in bone marrow CD34+ and peripheral blood nucleated cells. Clinically meaningful improvements in hemolysis markers (lactate dehydrogenase, haptoglobin, reticulocyte count, indirect bilirubin) were observed and maintained over time. Quality of life (QOL) measures showed clinically meaningful improvements compared to baseline. Most common adverse events (AEs) were nausea (69.6%), stomatitis (63%), vomiting (58.7%), febrile neutropenia (54.3%), headache (54.3%), abdominal pain (52.2%), and pruritis (50%). Most AEs and serious AEs (SAEs) occurred within first 6 months after exa-cel infusion. No participants had SAEs considered related to exa-cel; there were no study discontinuations or malignancies. As previously reported, there was 1 death from respiratory failure due to COVID-19 infection unrelated to exa-cel. Conclusion: Exa-cel demonstrated elimination of VOCs in 90% of participants that was maintained for up to 4.7 years. All participants had durable increases in Hb and HbF levels and stable allelic editing; clinically meaningful improvements were also seen in hemolysis markers and QOL measures. The safety profile of exa-cel remains consistent with myeloablative busulfan conditioning and autologous transplantation. These results confirm the potential for exa-cel to provide a one-time functional cure to patients with severe SCD.