A new induction protocol for the control of steroid refractory/dependent acute graft versus host disease with alefacept and tacrolimus.
OBJECTIVE
We have shown previously that alefacept is effective in acute steroid resistant/dependent and chronic extensive graft versus host disease (GvHD) with a protocol using timings similar to those used for psoriasis treatment. In this study, we describe the use of an alefacept induction (e.g. for 7 consecutive days) followed by a bi-weekly maintenance treatment in combination with tacrolimus for acute steroid resistant/dependent GvHD 1, 3.


METHODS
Sixteen patients were treated in this cohort, most with refractory GvHD. The pre-treatment GvHD grade ranged from 2 to 4 (median 3), involving the skin 16, gut 11 and liver 5.


RESULTS
Twelve out of the 16 patients showed a response. As with the first protocol, the response of GvHD in the skin was fastest. In contrast to our previous protocol, however, the gastro-intestinal (GI) GvHD response was faster (P=0.05 compared with the first cohort). A hepatic response was seen in 4/6 patients and was complete in three. All responses were durable, including mucocutaneous, gut and liver GvHD. In all responding patients we were able to decrease the steroid dose significantly and in seven it was completely withdrawn.


CONCLUSIONS
Alefacept induction is safe in acute steroid resistant/dependent GvHD and may be more effective therapeutically than our previous alefacept protocol. We speculate that alefacept initiates an allo-versus-allo cellular effect through its Fc receptor.
Shapira
Michael Y
MY
Department of Bone Marrow Transplantation and Cancer Immunotherapy, Hadassah-Hebrew University Medical Center, Jerusalem, Israel. mail: shapiram@hadassah.org.il
Resnick
Igor B
IB
Dray
Liliane
L
Aker
Memet
M
Stepensky
Polina
P
Elad
Sharon
S
Gesundeheidt
Benjamin
B
Samuel
Simcha
S
Or
Reuven
R
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D000077944:Alefacept; D002648:Child; D002675:Child, Preschool; D002985:Clinical Protocols; D003879:Dermatologic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011993:Recombinant Fusion Proteins / Q000009:adverse effects / Q000627:therapeutic use*; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*; D055815:Young Adult
D003879:Dermatologic Agents; D007166:Immunosuppressive Agents; D011993:Recombinant Fusion Proteins; D000077944:Alefacept; D016559:Tacrolimus