Control of Fulminant Juvenile Myelomonocytic Leukemia (JMML) Relapse and Gut GvHD III° with Purinethol Early after Unrelated Donor BMT.

Juvenile myelomonocytic leukemia (JMML) is a rare disease in childhood which can only be cured by stem cell transplantation. The major complication is relapse in up to half of the patients. The existance and efficacy of graft-versus-leukemia (GvL) in JMML is controversial and often associated with severe graft-versus-host disease (GvHD).

A 1,5 year old boy developed JMML and was transplanted from a 1 antigen mismatched UD (unmanipulated bone marrow, 8.5 Mio CD34/kg) after a CR consisting of Bu 16*1.25 mg/kg), Cy (2*60 mg/kg), Mel (1*140 mg/m2) and ATG (3*20 mg/kg). GvH prophylaxis consisted of CsA and very short MTX. The situation was further complicated by the intermittent presence of CMV, HHV-6 and EBV in the peripheral blood which was treated intermittently by intravenous ganciclovir.

Engraftment occurred on day + 16. GvHD III° of the skin only developed and was treated with corticosteroids, CsA and MMF. Chimerism was complete on day +28.

Beginning on day +45 an increasing autologous chimerism was detected. Therefore, immunosuppression was halted. Despite discontinuation of all immunosuppressants the autologous chimerism increased to 60–80% (d +63) and the peripheral leukocytes increased to approx 30,000/μl together with eosinophilia (d +60). Clinical signs of relapse (hepatomegaly and pulmonary obstruction) were also present. Thereafter, within a week, leukopenia and thrombocytopenia developed and the autologous chimerism decreased to 1–5%.

Coinciding with the apparent GvL effect severe GvHD reappeared. Skin GvHD II–III° developed, than gut GvDH III° with massive life threatening fluid and potassium loss (day +73).

In an attempt to treat both JMML and GvHD the antimetabolite purinethol 50 mg/m2 daily was given orally.

Since day + 98 always an complete chimerism was observed. Gut GvHD gradually improved without further immunosuppression. The boy is now at home without evidence of disease or active GvHD more than 1 year after relapse.

We speculate that in this case purinethol controlled not only the severe gut GvHD after BMT but also JMML.

This antimetabolite may therefore be considered as an immunosuppressant for GvHD when malignat relapse is also present or imminent.