Effects of Low-Dose Glucocorticoid Prophylaxis on Chronic Graft-versus-Host Disease and Graft-versus-Host Disease–Free, Relapse-Free Survival after Haploidentical Transplantation: Long-Term Follow-Up of a Controlled, Randomized Open-Label Trial

Abstract

A B S T R A C TThis long-term follow-up study evaluated the effects of corticosteroid prophylaxis on graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS) based on a controlled open-label randomized trial in which 228 allotransplant recipients were categorized as low risk (n = 83, group A) or high risk; patients at high risk were randomly assigned to receive (n = 72, group B) or not receive (n = 73, group C) low-dose methylprednisolone prophylaxis. The cumulative incidences of chronic GVHD, relapse, nonrelapse mortality, leukemia-free survival, overall survival, and GRFS were 60%, 19%, 16%, 68%, 73%, and 46%, respectively, in all cases. Compared with the patients in group C, the cases in group B experienced a lower cumulative incidence of moderate to severe chronic GVHD (42% versus 20%; P = .010), herpes zoster infection (28% versus 12%; P = .010), pulmonary infections (42% versus 21%; P = .040), and osteonecrosis of the femoral head (ONFH; 16% versus 6%; P = .045) as well as better GRFS (59% versus 33%; P = .017). Factors associated with GRFS included total dose of corticosteroid used in the first 100 days after transplantation (hazard ratio, 1.547; P = .015) and platelet recovery (hazard ratio, 1.456; P = .037). Our results suggest that low-dose glucocorticoid prophylaxis reduces GVHD and thus reduces the total dose of steroids, which might contribute to lower incidence of infections and ONFH and a superior GRFS, indicating that higher steroid doses are harmful. Reducing the total dose is of course beneficial. (ClinicalTrials.gov number, NCT01607580.)

Unmanipulated haploidentical haematopoietic cell transplantation with radiation‐free conditioning in Fanconi anaemia: A retrospective analysis from the Chinese Blood and Marrow Transplantation Registry Group

“…However, it must be noted that both ATG and PTCy are associated with delayed immune reconstitution and increased risk of viral reactivation and serious infection 43–45 . Prospective studies have demonstrated that prophylactic use of low‐dose glucocorticoids in haplo‐HCT can successfully reduce the incidence of aGvHD and cGvHD without increasing the risk of infectious diseases and corticosteroid‐related complications 46,47 . Given that severe aGvHD is one of the main contributors to transplantation‐related mortality 18 and cGvHD is another contributor to secondary malignancy, 15,18 prospective randomised clinical trials are needed to develop a better algorithm of GvHD prophylaxis in patients with FA receiving unmanipulated haplo‐HCT.…”

Fanconi anemia and haploidentical stem cell transplantation

“…This work describes two patients with FA diagnosis taken to HSCT with reduced‐intensity conditioning and GvHD prophylaxis with an adapted dose of PTCy. Given our prior experience with three patients who received the protocol reported in the literature, 12,15 of which only one survived and has moderate chronic GvHD; and the remaining patients had severe mucositis and bacteremia, herein, it was decided to modify the protocol by increasing the ATG dose, keeping the pre‐HSCT radiotherapy dose on day −6, skipping the Cy dose in conditioning and administering an adjusted dose of PTCy, as well as changing MMF to MTX 16 in the GvHD prophylaxis and adding low‐dose steroid, 17 in accordance with that already published, seeking to reduce toxicity and GvHD (Table 2). Both patients in this report tolerated the procedure and had excellent outcomes, with an early 100% chimerism result, without severe infectious complications or severe GvHD, demonstrating a promising strategy for these patients and opening the panorama for new higher‐scale studies.…”

Pacientes con enfermedad injerto contra huésped e infecciones asociadas al rechazo de trasplante

“…La fotoresis extracorpórea (FEC) es una terapia inmunomoduladora atractiva que evita la inmunosupresión generalizada, siendo este el tratamiento de segunda línea refractario a esteroides. Es por esto que la FEC consiste en infundir linfocitos irradiados con radiación ultravioleta e incubarlos con 8 -metoxipsoraleno, para regular los clones de células T activos y aumentar las células T reguladoras; aunque el número de estudios publicados es limitado, se demuestra eficacia 17,18 .…”