Chimeric Monoclonal CD-20 Antibody (Rituximab) for Steroid Refractory Acute Graft Versus Host Disease (SR-aGVHD): A Pilot Study
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Diagnosis of acute graft-versus-host disease (aGVHD) meeting the following criteria:
- Steroid-refractory and meeting any of the following organ-staging criteria:
- No change in the stage of skin aGVHD after treatment with
methylprednisolone at a dose of 2 mg/kg per day or more for 1 week
- Progression of aGVHD of skin by at least 1 stage OR no response of visceral
(liver, GI) aGVHD despite treatment with methylprednisolone at a dose of 2
mg/kg per day or more for at least 72 hours
- Progression of visceral aGVHD despite treatment with methylprednisolone at
a dose of 2 mg/kg per day or more for at least 48 hours
- Progression of visceral aGVHD to stage 4 after treatment with
methylprednisolone at a dose of 2 mg/kg per day or more for 24 hours
- Grade II-IV aGVHD requiring systemic therapy within 24-48 hours of diagnosis
- Biopsy confirmation of aGVHD is strongly recommended but not required
- No isolated upper gastrointestinal GVHD as sole manifestation of aGVHD
- No isolated grade I or II skin GVHD as sole manifestation of aGVHD
- Patients must have received prior corticosteroids at a dose of 2 mg/kg/day or
more for at least 72 hours as first-line aGVHD treatment
- Have undergone hematopoietic stem cell transplantation for any indication and from
any allogeneic graft and donor type (i.e., marrow or peripheral blood,
matched-related or matched-unrelated) within the past 100 days
- Absolute neutrophil count > 500/mm^3 times 3 days (must have evidence of
engraftment)
- No prior autologous or syngeneic transplantation
- No chronic GVHD, defined as GVHD occurring beyond 100 days of the hematopoietic
transplant
- No development of GVHD after prior donor lymphocyte infusion
- No post-transplantation lymphoproliferative disorder
- Patients failing to respond to second-line aGVHD treatment with infliximab or other
second-line therapy are allowed
- Rituximab is administered as 3rd-line aGVHD therapy
PATIENT CHARACTERISTICS:
- See Disease Characteristics
- Karnofsky performance status 30-100%
- Not pregnant or nursing
- Fertile patients must use effective contraception during and for 6 months after
completion of study therapy
- No uncontrolled infection (i.e., documented bacterial, viral, or fungal infection
within 72 hours prior to study entry)
- Concurrent prophylactic, empiric, or therapeutic use of antibiotics (i.e., taken
concurrently for a controlled infection) allowed
- Clostridium difficile infection allowed
- More than 8 weeks since documentation of any of the following opportunistic
infections:
- Pneumocystis carinii
- Aspergillosis
- Histoplasmosis
- Atypical mycobacterium infection
- Other pathogenic molds or fungi
- No hypotension believed to be secondary to sepsis syndrome or heart failure requiring
> 1 inotropic agent, or dopamine > 5 mcg/kg/min for blood pressure support
- No mechanical ventilatory support
- No relapsed, refractory, or second malignancies at the time of study entry
- No prior grade IV severe adverse reaction to rituximab
- No allergy to murine products
- No documented HIV infection
- No grade IV renal, hepatic, pulmonary, or neurologic toxicity
- No congestive heart failure, defined as cardiac dysfunction requiring inotropic
support other than dopamine at ≤ 5 mcg/kg/min
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No prior rituximab in the conditioning regimen for hematopoietic stem cell
transplantation
- No prior prophylactic immunosuppression tapered or stopped for treatment of leukemia
relapse or minimal residual disease
- More than 2 weeks since other prior investigational agents for GVHD treatment or
prophylaxis