Characteristics of graft‐versus‐host disease occurring after alemtuzumab‐containing allogeneic stem cell transplants: incidence, organ involvement, risk factors and survival

Abstract

Summary T‐cell depletion with alemtuzumab represents an effective form of graft‐versus‐host disease (GVHD) prophylaxis after allogeneic haematopoietic stem cell transplantation (allo‐HSCT); however, little is known regarding the impact of in vivo alemtuzumab on either the incidence or clinical characteristics of acute and chronic GVHD. We therefore studied 201 consecutive adult patients who received an alemtuzumab‐based, reduced‐intensity conditioned (RIC) allograft. With a median follow‐up of 24 months, the cumulative incidence of classic acute and late acute (persistent, recurrent and late onset) GVHD grades II–IV (grades III–IV) was 34% (13%) and 20% (8%) respectively; the cumulative incidence of classic chronic GVHD and overlap syndrome were 4% and 7% respectively. A previous diagnosis of classic acute GVHD is a risk factor for chronic GVHD (hazard ratio 10·91, 95% confidence interval 2·35–50·63, P = 0·0023) while late onset acute GVHD is not a risk factor for later development of chronic GVHD. Unrelated donor transplant is a risk factor for the development of classic acute GVHD but not for late onset or chronic GVHD. In conclusion, this study describes a distinctive pattern of GVHD following alemtuzumab‐RIC allografts, identifies the risk factors for GVHD development and provides prognostic information of patients with GVHD.

CD52‐negative T cells predict acute graft‐versus‐host disease after an alemtuzumab‐based conditioning regimen

“…Reduced-intensity conditioning HSCT protocols using alemtuzumab, are feasible to treat older and pretreated patients with low tumour-related mortality; however, despite TCD GVHD occurs to some extent. 4,[23][24][25][26] Different schedules and levels of alemtuzumab can contribute to clinical effects and different T-cell reconstitution pattern. [27][28][29] Patients treated with 'proximal alemtuzumab' (close to the time of graft infusion) developed more mixed chimerism 29 and less aGVHD compared with patients treated with 'distal alemtuzumab" (more distant from the time of graft infusion) schedules, whereas 'intermediate alemtuzumab' (e.g.…”

“…Patients were treated with RIC: fludarabine (30 mg/m 2 days À7 to À3), melphalan (140 mg/m 2 day 2) and alemtuzumab. 4,8,10 All patients in our cohort received viral/antifungal/anti-microbial prophylaxis with aciclovir, posaconazole, cotrimoxazole/trimethoprim and ciprofloxacin. GVHD prophylaxis contained cyclosporine A (day À1 to +50).…”

“…2 In alemtuzumab-treated patients >95% of CD3 pos CD4 pos T cells and >80% CD3 pos CD8 pos T cells were depleted. 3 In 2019, Finazzi et al 4 showed that despite TCD with alemtuzumab the incidence of aGVHD Grades II-IV (Grades III-IV) was 34% (13%) and of cGVHD was 4%.…”

“…In 2019, Finazzi et al 4 . showed that despite TCD with alemtuzumab the incidence of aGVHD Grades II–IV (Grades III–IV) was 34% (13%) and of cGVHD was 4%.…”

Current Preventions and Treatments of aGVHD: From Pharmacological Prophylaxis to Innovative Therapies

“…With a median follow-up of 24 months, the cumulative incidences of aGVHD and late acute GVHD grades II-IV (grades III-IV) were 34% (13%) and 20% (8%) respectively. Furthermore, the cumulative incidences of cGVHD and overlap syndrome were 4% and 7% respectively (76). Although Alemtuzumab administration before HSCT, from related or unrelated donors, resulted in a lower incidence of GVHD, it could remain in the blood at lympholytic level for 1 to 2 months after transplantation.…”