Pentostatin for High Risk and Refractory Chronic Graft Versus Host Disease in Children

Inclusion criteria:

* Allogeneic BMT or SCT recipients. Includes cord blood and peripheral blood.
* Age 0-21 years.

FOR REFRACTORY GROUP:

* Diagnosis of chronic GVHD, confirmed by biopsy of any organ after SCT. Given the variability among centers, biopsy needs to say, at the very least, "consistent with GVHD." If there is a medical contra-indication (such as severe sclerosis with poor wound healing) or the need for an open procedure to obtain a fascial biopsy then a photograph documenting the skin and abnormal ROM studies may be submitted instead. If current GVHD represents the same episode which was previously biopsied, then a new biopsy is not necessary. If the previous biopsy was for an episode that went into remission and this is a new episode of GVHD, then a new biopsy is necessary.

To be eligible for this portion of the study, a patient's chronic GVHD can be extensive or limited, as defined below:

* All subjects with extensive chronic GVHD are eligible. These subjects must meet the following criteria:

  * Generalized skin involvement (\>50% BSA)
  * OR Localized skin involvement and/or liver dysfunction plus at least one of the following:

    * Liver histology showing chronic aggressive hepatitis, bridging necrosis, cirrhosis, or ductopenia.
    * Eye involvement (Schirmer's test with \< 5 mm wetting)
    * Involvement of minor salivary glands or oral mucosa on lip biopsy
    * Involvement of any other target organs
  * OR Involvement of at least 2 target organs.(Target organs are listed below under "Examples of characteristic manifestations)
* Subjects with limited chronic GVHD (defined as those with skin involvement in less than 50% BSA or isolated organ involvement 51 are also eligible. Examples of these subjects would be those with limited sclerodermatous or fascial skin disease or oral disease that is unresponsive to therapy and may be debilitating to the patient. Subjects with isolated refractory liver chronic GVHD may go on study provided they have liver histology as above.

Examples of characteristic manifestations include:

* skin changes - rash, lichenoid changes, sclerodermatous changes, hypopigmentation, hyperpigmentation, loss of appendages (hair follicles, sweat glands), alopecia
* oral changes - erythema, lichenoid changes, ulceration
* hepatic involvement - obstructive jaundice, chronic hepatitis, cirrhosis
* GI involvement - nausea, vomiting, weight loss, esophageal dysmotility, malabsorption, chronic diarrhea, abdominal cramps
* sicca syndrome - dry eyes and mouth (decreased tearing, keratoconjunctivitis, oral mucosal erythema and ulcerations)
* other inflammatory conditions - myositis, arthritis, polyserositis

To be eligible for this portion of the study subjects must have refractory disease defined below:

* Development of new sites of disease while being treated for chronic GVHD\* (These criteria can be met at any time post-transplant after treatment for chronic GVHD has begun. This includes subjects who develop new sites of disease while on steroid therapy, tapering steroid therapy, or other therapy. The only necessary elements are TREATMENT of chronic GVHD and NEW area of disease. -OR-
* Progression of an initially affected site of chronic GVHD while being treated for chronic GVHD, the chronic GVHD worsens. This type of patient has worsening of any initially affected area at any time. This includes subjects that are judged to be steroid-dependent, and once a taper of steroids is initiated, they flare in the same organ. -OR-
* Failure to improve despite at least 1 month of standard therapy (These subjects have shown no response (not improved but not worse) to cGVHD therapy. These therapies include, but are not limited to:

  * Prednisone at an average of 0.5 mg/kg/day or equivalent steroid.
  * Another immunosuppressive regimen (e.g.. FK506/MMF or photopheresis).

FOR HIGH-RISK GROUP:

* The vast majority of these subjects will be identified at initial diagnosis of chronic GVHD and will be subjects progressing from acute to chronic. These subjects are likely to be on steroids for acute GVHD and have skin changes that are rapidly shifting from simple erythema to a lichenoid/pebbly appearance consistent with chronic GVHD. For inclusion into this arm, the following are required:

  * Extensive skin involvement (\>50%BSA) with either lichenoid or sclerodermatous changes.
  * Either one or both of the following high-risk features:

    * Thrombocytopenia (PLT\<100,000)
    * Progressive onset ( i.e. Changes suggestive of progression from acute to chronic). This includes, but is not limited to, skin becoming increasingly scaly, pebbly, raised, and lymphedematous. It is not unusual to see this transition even before day 100, especially in non-myeloablative SCT and DLI. If there are any questions regarding these changes and whether they qualify, call the PI, Dr. David Jacobsohn, 773-880-3694.
  * A biopsy after SCT showing acute or chronic GVHD. A biopsy showing acute GVHD is acceptable if the clinical picture is progressing to chronic GVHD.
  * Patient is on prednisone ≥2 mg/kg/day (or equivalent dose if on another steroid) and has received more than 7 days of therapy.

Exclusion Criteria:

* More than two previous regimens to treat chronic GVHD. A regimen for the purpose of this study is defined as an adequate trial of an immunosuppressive or immunosuppressive combination (patient was given drug or drugs for 3 months unless there was clear progression during regimen).
* Calculated Cr. Clearance\<30 ml/min/1.73m2
* Active infection not responding to oral or IV antibiotics.
* Subjects and families unwilling to firmly commit to return for follow-up doses and appointments.
* Use of any investigational agent in the past 30 days (this does not include the use of licensed agents for indications not listed in the package insert).
* Pregnancy or nursing mother; Females of child-bearing potential and sexually active males should use effective contraception while on study.
* Active veno-occlusive disease of the liver.
* Bronchiolitis obliterans (defined for the purpose of this study by respiratory symptoms such as shortness of breath or cough and FEV1\<50%).
* Karnofsky performance score less than 40 (or Lansky performance less than 40 in subjects under 16 years of age).