Editor’s Note: The 50th European Society for Blood and Marrow Transplantation (EBMT) Annual Meeting was held in Glasgow, UK, from April 14th to 17th, 2024. The conference focused on the latest developments in stem cell transplantation and cell therapy, pushing forward better clinical outcomes for patients with hematologic diseases and blood cancers. At this meeting, Dr. Gao’s team presented six research findings, covering innovative explorations and practices in hematopoietic stem cell transplantation, as well as the combined application of CAR-T and hematopoietic stem cell transplantation. They shared advanced concepts and research findings, contributing China’s wisdom to the global stage and sharing innovative results with the world. This article includes a translation and compilation of two posters from Professor Tong Wu’s team for the enjoyment of our readers.
Maintenance Therapy with Olaparib Following Allogeneic Hematopoietic Stem Cell Transplantation in Malignant Hematologic Diseases with TP53 Mutation
Research Background:
The mutated TP53 protein interacts with DNA repair proteins, impacting the repair of DNA double-strand breaks (DSBs) and reducing the cell’s ability to repair these breaks. In cells, the repair of DNA single-strand breaks (SSBs) also requires the involvement of PARP. Using PARP inhibitors to block the single-strand repair (SSR) in tumor cells can induce synthetic lethality in tumor cells with TP53 mutations. PARP inhibitors could be a potential treatment for malignant hematologic diseases with TP53 mutations. This study retrospectively analyzed the efficacy and safety of using the PARP inhibitor olaparib as maintenance therapy after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with malignant hematologic diseases harboring TP53 mutations.
Research Methods:
This study included 71 patients with TP53-mutated malignant hematologic diseases who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) at our hospital from September 2018 to November 2022. The diagnoses included acute myeloid leukemia (17 cases, 23.94%), acute B-cell lymphoblastic leukemia (36 cases, 50.70%), T-lymphoblastic lymphoma/leukemia (8 cases, 11.27%), and non-Hodgkin lymphoma (10 cases, 14.08%). Of these, 29 patients (40.85%) who relapsed received second-line treatment, and 21 patients (29.58%) underwent a second transplantation. The median age was 20.35 years (range 1.6-64.7). Before transplantation, 33 patients (46.48%) had extramedullary disease and 27 patients (38.03%) had chromosomal abnormalities. Prior to transplant, 45 patients were in complete remission and 26 were not in remission. The types of transplants included 3 sibling matched, 17 unrelated, and 51 haploidentical. The myeloablative conditioning regimens used were either total body irradiation/fludarabine (40 cases, 56.34%) or busulfan/fludarabine (31 cases, 43.66%). Post-transplant, 32 patients (45.07%) received maintenance therapy with olaparib (olaparib group), and 39 patients (54.93%) did not receive any maintenance therapy (control group). There were no significant differences in clinical characteristics between the two groups. The median time to start olaparib treatment was 67 days (range 25-496) post-transplant, with a median dose of 75 mg (range 50-150 mg) twice weekly. The median duration of olaparib maintenance therapy was 10 months (range 0.24-45 months).
Research Results:
The median follow-up time was 12.30 months (range 13.72-21.28), with overall survival (OS) rates and progression-free survival (PFS) rates of 56.36% (43.78%-67.16%) and 51.33% (39.04%-62.34%), respectively. In the olaparib group, the OS and PFS rates were 90.63% (73.69%-96.88%) and 84.38% (66.46%-93.18%), respectively. In the control group, the OS and PFS rates were 25.51% (12.44%-40.85%) and 23.52% (11.33%-38.21%), respectively. Maintenance therapy with olaparib significantly improved OS (P<0.001) and PFS (P<0.001).
The recurrence rate in the olaparib group was significantly lower than in the control group (25% vs. 53.85%, P<0.014). Eight patients (11.3%) temporarily discontinued olaparib, and eleven patients (15.5%) adjusted the dose due to side effects. Grade 2 adverse effects occurred during olaparib treatment, but no ≥ grade 3 adverse effects were observed. The most common side effects included neutropenia, anemia, thrombocytopenia, and epistaxis, all of which were tolerable and reversible. No organ toxicity or drug-related deaths were observed.
Study Conclusion:
The study indicates that maintenance therapy with olaparib post-transplantation for patients with TP53-mutated malignant hematologic diseases is safe and effective, significantly reducing recurrence rates and improving OS and PFS. Future studies should conduct larger prospective, randomized controlled trials.
Nursing Care for a Patient with Extensive Exfoliative Skin Lesions Following a Second Transplant for Refractory Relapsed Acute Myeloid Leukemia
Study Purpose:
To summarize the nursing outcomes for a case of extensive exfoliative skin lesions occurring after a second HSCT in a patient with acute myeloid leukemia.
Study Methods:
The patient, a 49-year-old male with a 10-year history of acute myeloid leukemia, underwent a second HSCT on November 6, 2023. Upon admission, he had chronic illness presentation, bilateral pneumonia, osteonecrosis of the femoral head, and lower limb paralysis. He was preconditioned with BU/VM-26/FLU+Ara-C/ATG/Meccnu and received a haploidentical peripheral blood stem cell transplant from his son on November 23. The patient experienced high fever and diarrhea two days before the transplant, with subsequent cultures indicating Klebsiella pneumoniae infection. On day 01 post-transplant, he developed cytokine release syndrome, followed by acute renal failure on day 8, requiring plasma exchange, and acute respiratory failure on day 10, requiring non-invasive mechanical ventilation. Starting from day +1 post-transplant, the patient showed scattered skin lesions on his limbs, which extended to his lower back and abdomen by day +4. By day +14, after removing the ventilator, 90% of the skin on his back and buttocks was damaged, red, exuding, painful, and extremely fragile. Skin care included thick application of Pi Fu Ling ointment and Jinyufu paste, covered with sterile gauze, and wrapped in sterile sheets, with daily dressing changes.
Study Results:
The skin redness and pain progressively decreased, the area of redness shrank, and the patient showed no pain during dressing changes. On the fifth day of treatment, there was a significant reduction in symptoms, with skin islands appearing on the sixth day, and the fragile skin becoming firmer. By the seventh day, all skin redness disappeared, extensive skin islands emerged, and the patient was completely pain-free, with all damaged skin healed.
Study Conclusion:
After 10 years of treatment, the patient experienced graft rejection, infections, and relapse following the first transplant, leading to severe organ dysfunction. This second transplant involved intensive pre-treatment, immunosuppressants, and significant steroid use for cytokine management, which led to complications such as electrolyte imbalances, hyperglycemia, edema, and respiratory failure. These factors all contributed to the high risk of skin damage. The medical team utilized cell regeneration technology from BAK Pharmaceuticals and applied Jinyufu ointment, which healed the patient’s skin completely within just 10 days. This approach prevented further systemic infections, alleviated the patient’s suffering, and reduced additional treatment costs.
