Total marrow and lymphoid irradiation as conditioning in haploidentical transplant with posttransplant cyclophosphamide.
Monzr M Al MalkiJoycelynne PalmerNi-Chun TsaiSally MokhtariSusanta HuiWeimin TsaiIbrahim AldossHaris AliAhmed AribiThai CaoMathew MeiKaramjeet S SandhuTanya SiddiqiStephen J FormanRyotaro NakamuraGuido MarcucciAnthony SteinJeffrey Y C WongJoseph RosenthalPublished in: Blood advances (2022)
Posttransplant cyclophosphamide (PTCy) platform has shown low rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after haploidentical hematopoietic cell transplantation (HaploHCT). However, because of the limited disease control, relapse rate remains a major cause of treatment failure in high-risk patients. Total marrow and lymphoid irradiation (TMLI) allows for delivery of high radiation to bone marrow and other targeted structures, without increasing off-target radiation exposure and toxicity to end organs. In this phase 1 trial, 31 patients with high-risk and/or active primary refractory leukemias or myelodysplastic syndrome underwent peripheral blood stem cell HaploHCT with TMLI, fludarabine, and cyclophosphamide as the conditioning regimen. Radiation dose was escalated in increments of 200 cGy (1200-2000 cGy). GVHD prophylaxis was PTCy with tacrolimus/mycophenolate mofetil. Grade 2 toxicities by the Bearman scale were mucositis (n = 1), hepatic (n = 3), gastrointestinal (n = 5), and cardiac (n = 2). One patient (1800 cGy) experienced grade 3 pulmonary toxicity (dose-limiting toxicity). At a follow-up duration of 23.9 months for the whole cohort; 2-year NRM was 13%. Cumulative incidence of day 100 grade 2 to 4 and 3 to 4 acute GVHD was 52% and 6%, respectively. Chronic GVHD at 2 years was 35%. For patients treated with 2000 cGy, with a median follow-up duration of 12.3 months, 1-year relapse/progression, progression-free survival, and overall survival rates were 17%, 74%, and 83%, respectively. In conclusion, HaploHCT-TMLI with PTCy was safe and feasible in our high-risk patient population with promising outcomes.
Keyphrases
- free survival
- peripheral blood
- bone marrow
- allogeneic hematopoietic stem cell transplantation
- high dose
- stem cells
- low dose
- stem cell transplantation
- end stage renal disease
- radiation induced
- oxidative stress
- case report
- ejection fraction
- newly diagnosed
- chronic kidney disease
- risk factors
- liver failure
- acute lymphoblastic leukemia
- mesenchymal stem cells
- left ventricular
- acute myeloid leukemia
- type diabetes
- high throughput
- high resolution
- cardiovascular disease
- peritoneal dialysis
- oxide nanoparticles
- respiratory failure
- radiation therapy
- drug delivery
- hepatitis b virus
- atrial fibrillation
- extracorporeal membrane oxygenation
- adipose tissue
- single cell
- skeletal muscle
- mechanical ventilation