Preliminary Results From a Single Institutional Prospective Study of Alemtuzumab for the Treatment of Steroid Refractory Acute Graft Versus Host Disease in Pediatrics

Introduction

No clear second line agent exists for the treatment of steroid refractory acute graft versus host disease (SR-aGVHD) in children.  Alemtuzumab is associated with partial or complete responses in 50-94% of adult patients.  Studies are lacking in pediatric patients.  The optimal dose for young patients is unknown.  Here we present the first phase of a single center dose-escalation study of alemtuzumab for treatment of acute SR-aGVHD in pediatric patients. 

Methods

Patients were prospectively enrolled at the time of diagnosis of grades II-IV acute GVHD.  Patients were initially treated with 4mg/kg/day methylprednisolone.  If patients failed to improve within 5 days, or worsened within 48 hours, SR-aGVHD was diagnosed and alemtuzumab was administered at 0.2 mg/kg/day for 5 consecutive days (maximum cumulative dose of 31mg).  Additional 0.2mg/kg doses were given on days 15, 22 and 29 (maximum dose 10mg/dose).  Patients were monitored weekly for response.  Partial response (PR) was defined as improvement in stage of GVHD before 28 days following first alemtuzumab administration, and complete response (CR) was defined as achievement of grade zero GVHD by 28 days following the first alemtuzumab administration. 

Results

Six patients have been enrolled and 5 patients with grades III (n=4) or IV (n=1) GVHD were treated with alemtuzumab so far.  Median age was 12 years (range 1.9-27 years).  Organs involved included skin (n=4), gastrointestinal tract (n=4) and liver (n=2) (Table I).  Forty percent of patients (n=2) had a CR. Sixty percent of patients (n=3) had a PR.  Adverse effects included transient neutropenia or thrombocytopenia (n=3), fever (n=2), or asymptomatic EBV viremia (n=2) and/or adenovirus viremia (n=2).

Conclusion

Alemtuzumab is an active agent for the treatment of SR-a GVHD in pediatric patients.  Further dose escalation may increase complete response rates and establish an optimal regimen for successful therapy.

Table I. Response to alemtuzumab

Patient	Organ(s) Involved	Grade at Alemtuzumab Administration	Grade at Day 28	Stage at Alemtuzumab Administration	Stage at day 6	Stage at day 10	Stage at day 14	Stage at day 21	Stage at day 28
1	Skin GI	III	0	III III	I III	0 0	0 0	0 0	0 0
2	Skin GI Liver	III	III	I IV II	0 III II	0 III II	0 III II	0 I II	0 II II
3	Skin GI	III	III	II III	I III	0 III	End of study therapy
4	Skin Liver	IV	IV	II IV	I IV	0 IV	End of study therapy
5	GI	III	0	IV	I	I	I	0	0