Experience with 100 Allogeneic Marrow Grafts Using Cyclosporin-A (CYA) for Prophylaxis Against GVHD

Of the 100 patients 29 had AML, 30 ALL, 24 CML and 17 SAA. Median age was 28 years (442). Median follow up is 26 months (7–55). Patients with leukemia were conditioned with Cy 2×60 mg/kg and 10 Gy TBI. Patients with SAA were given Cy 4×50 mg/kg and donor buffy coat from 4 units of blood on 5 successive days after BMT. 95 patients had an HLA-identical sibling donor. 5 times an HLA-haploidentical family member served as a donor. The CyA protocol was changed three times (1). We always started with a parenteral application on day −1 and later changed to oral CyA 12.5 mg/kg in a single daily dose up to 6 months and then gradually reduced and stopped at one year. The dose was adjusted primarly to the serum creatinine level but to some extent also to the blood CyA through level. Patients developing grade II or greater GvHD were treated with bolus methylprednisolone in addition. I g was given as a 24-hour infusion on the first day, followed by 500 mg on the second day. Then the dose was reduced to 0.5 mg/kg. Compared to our previous experience with MTX, CyA did not influence the incidence of GvHD, but decreased its severity. In patients who died from transplant related mortality it was often difficult to distinguish between GvHD and/or viral infections. 29 of 51 patients transplanted for acute leukemia in first remission and CML in chronic phase became long term disease free survivors (57%). Only 8 of 32 patients transplanted in later stages of the disease survived (25%) without evidence of leukemia. In the first group relapse was the cause of death in 15%, in the second one in 85%. Fatal transplant related complications were comparable in both groups: ± 15% with an unusally low incidence of interstitial pneumonia of 4%. In 16 patients with SAA BMT was the primary treatment of their disease. 10 of them are living and well (62.5%) without any chronic problems. Of the 6 deaths 3 were due to acute GvHD, 1 to cardiac failure, 1 to CMV-infection and one to rejection. One patient with SAA had ALG as primary treatment. He had many transfusions from family members. His conditioning consisted of 10 Gy TBI. This patient never showed any evidence of engraftment and died. The 5 patients with haploidentical transplants all had leukemia. They did rather poorly: only 1 became a long term disease free survivor: 3 died of acute GvHD, one of leukemic relapse after having had severe GvHD. Several side effects of CyA were seen. They proved to be reversible and subsided upon dose reduction. Renal insufficiency, mild hepatic dysfunction, facial edema, tremor and anorexia were the most frequent ones. 4 patients had fits that responded to antiepileptic therapy and 2 had reversible facial nerve palsies. Reversible cotton wool lesions in the retina were seen in 5 patients. Upon stopping CyA at one year 40% of the patients developed signs of acute GvHD which subsided upon resumption of the drug, proving its therapeutic efficacy in the treatment of GvHD. Only one patient has severe chronic GvHD. It is restricted to the liver and presents like primary biliary cirrhosis. From this experience we conclude that CyA has markedly reduced our transplant related mortality in particular from interstitial pneumonia. In our study age did not play an important role for transplant related mortality between the age of 10 and 40 years. Leukemic relapse remains a major problem in particular in patients transplanted in late stages of leukemia, In our limited experience with HLA-haploidentical BMT CyA proved to be of little or no value in preventing severe GvHD. No chronic renal insufficiency or other serious long term side effects of CyA were observed.