PubMed · 4550583
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C F Zukoski. 1972. Transplantation.. https://pubmed.ncbi.nlm.nih.gov/4550583/
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BACKGROUND: Hypoplastic myelodysplastic syndrome (MDS) is characterized by dysplasia and hypocellularity. The treatment of choice for young patients is bone marrow transplantation. METHODS: This report describes the effect of immunosuppressive therapy in two patients with hypoplastic MDS for whom no suitable bone marrow donors were available. RESULTS: Both patients had no human lymphocyte antigen-identical siblings and no suitable matched unrelated donor could be found. They received cyclosporin A (CsA), antithymocyte globulin (ATG), or a combination of the two. Treatment with CsA, ATG, or the combination led to clinical improvement (resolution of transfusion requirement), increase of bone marrow cellularity, and the disappearance of dysplastic characteristics in the two patients with hypoplastic MDS. At the time of recurrence, this disease was still responsive to immunosuppressive therapy. CONCLUSIONS: Treatment with ATG and CsA can be an attractive alternative for patients with hypoplastic MDS for whom there is no possibility of bone marrow transplantation.
BACKGROUND: Refractory rejection and cyclosporine (CsA)-induced nephropathy remain important causes of renal allograft loss. Previous studies demonstrated that 70-85% of the episodes of refractory acute rejection (AR) occurring in renal allograft recipients on a CsA-based immunosuppressive regimen could be salvaged by conversion to tacrolimus. No data are available regarding the correlation between allograft histology at the time of conversion and the response to tacrolimus. We examined the response to tacrolimus conversion in relation to preconversion biopsies stratified by the Banff criteria. METHODS: Since May 1992, we have converted 22 patients from CsA to tacrolimus as part of a rescue protocol. We report on 18 patients in whom 6-month follow-up was available after conversion for biopsy-proven AR (n=13) or CsA toxicity (n=5). Sixteen patients were recipients of renal allografts, including three second transplants, and two were recipients of kidney-pancreas transplants. All patients with AR were treated with one or more courses of methylprednisolone and OKT3 before conversion. Renal allograft biopsies were interpreted by a transplant pathologist blinded to the clinical history, and graded according to the Banff criteria. Responses to tacrolimus were scored as improved (creatinine returned to within 150% of baseline), stabilized (creatinine rise arrested), or failed (returned to dialysis). RESULTS; Mean follow-up was 17.3+/-8 months. Fourteen of 18 patients (78%) showed improvement or stabilization in renal function as assessed by creatinine at 6 months or 1 year (when available). Of the 13 patients with histological AR, nine (69%) improved, including five of six with borderline AR, two of three with grade I AR, and two of four with grade II AR. Of the four other patients with AR, two stabilized and two failed. Three of five patients with severe clinical rejection requiring dialysis (range 2-16 weeks) recovered renal function after conversion. Of five patients with CsA toxicity, two (40%) improved. Seven of eight patients who were converted to tacrolimus less than 90 days after transplantation improved, compared with only 4 of 10 who were converted more than 90 days after transplantation. No grafts were lost in patients with a creatinine <3.0 mg/dl at the time of conversion versus two of seven grafts lost when the creatinine was 3.1-5.0 mg/dl and two of eight grafts lost when the creatinine was >5.0 mg/dl. CONCLUSION: The majority of steroid and antilymphocyte antibody (OKT3 or ATGAM) unresponsive rejections in patients on CsA-based immunosuppression will improve or stabilize after conversion to tacrolimus. There was no correlation with allograft histology stratified by the Banff criteria and the response to tacrolimus. Although there was a trend toward a poorer response with more severe histological rejection, higher serum creatinine at the time of conversion, and longer time from transplantation to conversion, favorable responses were noted in all groups. This indicates that a trial of conversion is warranted, irrespective of the histological severity of injury.
We analyzed the influence on allograft survival of pretransplant panel reactive antibodies (PRA) < 10%, PRA > 10%, autoantibodies, cold antibodies and a positive B cell crossmatch in 807 renal and 237 cardiac transplant recipients. Donors and recipients were predominantly of mixed ancestry (Khoi, San, Xhosa and Caucasoid). Log rank analysis showed that PRA < 10%, cold antibodies, and a positive B cell cross-match did not influence allograft survival. Autoantibodies were present only in renal recipients; they appeared to have a beneficial effect on allograft survival (P = 0.06). PRA > 10% appeared to have a detrimental effect on allograft survival in both renal (P = 0.07) and cardiac (P = 0.06) recipients. Since autoantibodies and PRA > 10% had opposing effects, the results of renal recipients were reanalyzed after omission of the recipients with autoantibodies and coexisting PRA > 10%. This resulted in augmentation of the protective effect for autoantibodies (P = 0.027) and of the detrimental effect for PRA > 10% (P = 0.020). Two-year survival curves showed that when autoantibodies coexisted with PRA > 10%, the long term, but not the short-term, detrimental effect of PRA > 10% was attenuated. Patients with a positive B cell cross-match clustered in the PRA > 10% group in both renal (PRA negative vs. PRA < 10%; P = 0.0251; PRA < 10% vs. PRA > 10%: P = 0.0011) and cardiac (PRA negative vs. PRA > 10%: P = 0.0085) recipients. We conclude that PRA > 10% is the best indicator to identify recipients at high risk for rejection, and that the influence of antibodies on graft survival can not reliably be established without taking coexisting antibodies into account.