Short-term methotrexate could reduce early immune reactions and improve outcomes in umbilical cord blood transplantation for adults

Abstract

Post transplant immune disorders are problematic in cord blood transplantation (CBT) for adult patients, and optimal prophylaxis has not been established. We investigated whether intensive graft-versus-host disease (GVHD) prophylaxis using short-term methotrexate (MTX) has a prognostic impact on CBT. Post-CBT immune reactions were classified according to time course as pre-engraftment immune reaction (PIR), engraftment syndrome (ES) or acute GVHD. Between March 2001 and November 2005, a total of 77 patients underwent CBT at eight transplantation centers. Median age was 48 years (range, 18-69 years). Preparative regimens comprised myeloablative (n ¼ 31) or reduced-intensity (n ¼ 46). Acute GVHD prophylaxis included cyclosporine alone (n ¼ 23), tacrolimus alone (n ¼ 12), cyclosporine plus MTX (n ¼ 17), tacrolimus plus short-term MTX (n ¼ 23) or cyclosporine plus methylprednisolone (n ¼ 2). Cumulative incidences of PIR, ES and grade II-IV GVHD were 36, 12 and 23%, respectively. Short-term MTX exerted significant favorable effects on post-CBT immune reactions (hazard ratio, 0.55; 95% confidence interval (95% CI), 0.31-0.98; P ¼ 0.04) in multivariate analysis. Overall survival rates for patients with and without short-term MTX at day 180 were 59% (95% CI, 42-73%) and 16% (95% CI, 6.6-30%) (P ¼ 0.0001), respectively. Shortterm MTX could offer one optimal regimen to reduce immune reactions and improve outcomes in CBT.

High incidence of graft failure in unrelated cord blood transplantation using a reduced-intensity preparative regimen consisting of fludarabine and melphalan

“…8 On the basis of this finding, we used tacrolimus and MTX for GVHD prophylaxis. However, this intensive regimen may suppress donor T cells and the proliferative capacity of hematopoietic cells, thereby increasing the risk of graft failure.…”

“…7 Post transplant immune reactions were classified into three subgroups ( Table 2). 8 The patients' characteristics and clinical courses are shown in Tables 1 and 2, respectively. The median number of infused total nucleated cells was 2.5 Â 10 7 /kg (range, 2.1-5.3 Â 10 7 /kg).…”

The syndrome of inappropriate secretion of antidiuretic hormone associated with SCT: clinical differences following SCT using cord blood and BM/peripheral blood

“…However, the hypothesis that SIADH following SCT treatment is related to the expansion of donor cells is not likely because patients with SIADH following CBSCT had an approximate 3 week earlier onset and one-third of the WBC count at the onset compared to those with SIADH following BMT/PBSCT. The difference in cytokine reactions between CBSCT and BMT/PBSCT, such as pre-engraftment immune reactions proposed as an early phenotype of post-CBSCT immune reaction, 16,17 may explain these clinical differences.…”

Identification of molecular markers for pre-engraftment immune reactions after cord blood transplantation by SELDI-TOF MS

“…GVHD prophylaxis with tacrolimus, compared with CsA, is less likely to be associated with PIR 3,4 and the addition of MTX may further reduce the risk. 5,6 It has been speculated that cytokines induced by the initial immune/inflammation reaction are the primary cause of PIR, but no data are available to confirm this supposition. To clarify this question, we evaluated the protein expression profile of serum in CBT recipients using a surface-enhanced laser desorption/ionization time-of-flight mass spectroscopy (SELDI-TOF MS) system and found potential markers for PIR.…”