Use of CAMPATH-1H as Graft-Versus-Host Disease Prophylaxis in Myeloablative Unrelated Donor Transplants.

Abstract

Graft-versus-host disease (GvHD) remains a frequent, morbid, potentially fatal, and costly complication of allogeneic stem cell transplantation (alloSCT) particularly when utilizing stem cells from unrelated HLA-matched donors (URD). Optimal GvHD prophylaxis in URD transplants remains uncertain. With standard post-alloSCT tacrolimus (FK) and minidose-methotrexate (MTX) chemoprophylaxis the incidence of acute GvHD approaches 50–75% in adult recipients of URD stem cells without T-cell depletion (TCD). Severe acute GvHD (grade III-IV) occurs in about 30% of these patients (pts), with an associated risk of mortality >80%. TCD is commonly employed but is associated with increased risk of disease recurrence and graft rejection. In this abstract we report observations from 20 pts who received CAMPATH-1H pre-alloSCT for GvHD prevention with a myeloablative (18/20 TBI-containing) conditioning regimen and URD stem cells. There were 2 cohorts of patients - Pts 1-10 (A) were treated with 5 days of CAMPATH; Pts 11–20 (B) were treated with 3 days of CAMPATH (20mg/d). All pts received FK and MTX GvHD prophylaxis. All pts had hematologic malignancies; 12 of 20 with >CR2 or relapsed/refractory disease at the time of conditioning. All pts received standard infection prophylaxis through at least day 100; CMV PCR was obtained weekly with any positive result prompting empiric therapy. Pts were evaluated for ANC recovery by day 30, sustained donor engraftment, presence of GvHD before and after day 100, and disease-free survival at day 100. ANC >500 for 3 consecutive days occurred in 18/20 patients by day 30 - one pt died before day 30 and one had primary engraftment failure (PEF). 17/20 pts were alive and evaluable at day 100 - 13/17 had full donor chimerism at day 100: 1 pt transplanted with refractory disease had disease recurrence, 2 pts had received suboptimal <2X106/kg CD34 cells, and 1 was the pt with PEF. No pts developed severe acute GvHD. There have been no deaths attributable to acute or chronic GvHD. At this report 7/20 pts are alive (6/7 from cohort B) at a median follow-up of 20 mos - 5 pts alive >1 yr and 1 pt > 2 yrs. Of note, the frequency and severity of viral infections, and host failure to antiviral therapy prompted a dose reduction of CAMPATH that defines cohorts A & B. 7/20 pts had reactivation of CMV - CMV as the cause of death in 4 and multiple viral infections (including CMV) in another. 9/20 patients had symptomatic BK viruria and 7/20 developed HSV infections requiring IV therapy. 4 of cohort A and 2 of cohort B had multiple co-existent viral infections. 7/10 in cohort A and 3/10 in cohort B succumbed to infections. Severe acute or chronic GvHD does not occur with this prophylaxis at either dose in our 2 cohorts. Use of CAMPATH-1H for GvHD prophylaxis is highly effective in preventing GvHD. The frequency and severity of viral infections require aggressive monitoring and empiric therapy. Consideration should be given to the lower dose use as GvHD prophylaxis. Pt CMV PCR(+) BKV in urine HSV (+) site other viral infexns cause of death 1 graft fx/sepsis 2 adenovirus 3 X X echovirus viral infexns 4 X X X relapse 5 X relapse 6 X X X CMV 7 X fungal/mucor 8 X relapse 9 X X X sepsis/ARDS 10 PE 11 X X CMV/sepsis 12 X rhino/paraflu 13 14 X 15 X 16 17 X X X toxoplasmosis 18 X CMV/ICH 19 graft fx/sepsis 20