Reduced-intensity stem cell allografting for PNH patients in the eculizumab era: The Mexican experience

Abstract

Background Paroxysmal nocturnal haemoglobinuria (PNH) presents as two major entities: the classical form, predominantly haemolytic and a secondary type with marrow failure and resultant aplastic anaemia (AA-PNH). Currently, the treatment of choice of the haemolytic variant is eculizumab; however, the most frequent form of PNH in México is AA-PNH. Patients and methods Six consecutive AA-PNH patients with HLA-identical siblings were allografted in two institutions in México, employing a reduced-intensity conditioning regimen for stem cell transplantation (RIST) conducted on an outpatient basis. Results Median age of the patients was 37 years (range 25-48). The patients were given a median of 5.4 × 10(6)/kg allogeneic CD34(+) cells, using 1-3 apheresis procedures. Median time to achieve above 0.5 × 10(9)/l granulocytes was 21 days, whereas median time to achieve above 20 × 10(9)/l platelets was 17 days. Five patients are alive for 330-3150 days (median 1437) after the allograft. The 3150-day overall survival is 83.3%, whereas median survival has not been reached, being above 3150 days. Conclusion We have shown that hypoplastic PNH patients can be allografted safely using RIST and that the long-term results are adequate, the cost-benefit ratio of this treatment being reasonable. Additional studies are needed to confirm the usefulness of RIST in the treatment of AA-PNH.

Hematopoietic Stem Cell Transplantation for Patients with Paroxysmal Nocturnal Hemoglobinuria with or Without Aplastic Anemia: Multicenter Turkish Experience

“…The median age at the time of transplantation was 32 and the oldest patient was 51 years of age. In the literature, the median ages of patients were generally in the range of 24.5-37 years, but a patient as old as 60 years was transplanted [ 11 , 12 , 15 , 16 , 17 , 18 ]. The median time to transplantation was 36 months in our cohort, and patients received different therapies, including eculizumab (21 patients with a median of 24 months; minumum-maximum: 1-44 months).…”

“…Considering the rarity of this disease and other treatment options, although prospective randomized studies are lacking in the literature, the safety and efficiency of RIC regimens were demonstrated in small series [ 17 , 22 ]. By integrating RIC regimens with allo-HCT for PNH patients, the mortality and morbidity rates have been reduced, obviating the need for more potentially toxic myeloablative therapies [ 16 , 23 ].…”

Recent advances on ISRU technologies and study of microgravity impact on blood cells for deep space exploration

“…Exposure to microgravity during space flight is known to involve a variety of health risks to the human body, increasing vulnerability to secondary conditions like radiation effects and physiological changes such as muscle atrophy, lysis, neocytolysis, metabolic variations, and hydrostatic pressure changes (Schimmerling, 1995;Schcolnik-Cabrera et al, 2014;Buonanno et al, 2015). Microgravity conditions and radiation can stimulate a variety of stressors in astronauts during spaceflight with negative consequences for their health (Garrett-Bakelman et al, 2019;Afshinnekoo et al, 2020).…”

Paroxysmal nocturnal hemoglobinuria: role of the complement system, pathogenesis, and pathophysiology

“…14 Because of the rarity of PNH, the incidence and prevalence rates have been poorly reported and have likely been underestimated. 12,15 However, for stakeholders to best night (nocturnal) hemoglobin occurring in the urine (hemoglobinuria, passing of breakdown product of RBCs into urine). 8 However, hemoglobin in the urine may not always be visible to the eye, and not every patient with PNH presents with frank hemoglobinuria.…”