WT1 peptide vaccination in combination with imatinib therapy for a patient with CML in the chronic phase.

Although tyrosine kinase inhibitors is effective for dramatically reducing CML cells, it might be difficult to eradicate completely the CML stem cells. We aimed to clarify the safety and effects of WT1 peptide vaccination in combination with imatinib therapy for a CML patient. A 51 year-old male with CML in CP, who showed a resistance against imatinib therapy for 2.5 years, began to be treated with 9 mer modified-type WT1 peptides in combination with standard dose of imatinib. Although every 2-week-administration of WT1 peptides for 22 weeks did not show definite effects on the quantification of bcr-abl transcripts, by changing the administration from every 2 weeks to 4 weeks bcr-abl transcripts decreased remarkably. After 11 months of every 4-week-administration of the peptides and 12 months post cessation of the peptides bcr-abl transcripts achieved to the level below detection by RQ/RT-PCR (complete molecular response). WT1/MHC tetramer(+)CD8(+) CTLs, which appeared after the second administration of WT1 peptides and remained more than 15 in number among 10(6) CD8(+) T cells throughout the administration of WT1 peptides, are still present in the blood on 14th month post cessation of the peptides. An in vitro study as to the cytotoxicity of lymphocytes induced by mixed lymphocyte peptide culture demonstrated that cultured lymphocytes possessed cytotoxicity against WT1 expressing leukemia cells and the cytotoxicity was WT1-specific and MHC class I restricted. The present study showed that WT1 peptide vaccination in combination with TKI is feasible and effective in the therapy for imatinib-resistant CML.

Switching of donor cells after urgent second cord blood transplantation for suspected graft failure.

Cord blood transplantation (CBT) is being increasingly performed in adults and is now becoming a standard therapeutic alternative to bone marrow transplantation; however, graft failure is one of the associated problems of CBT in adults. A 44-year-old woman with acute myelogenous leukemia in partial remission received an unrelated CBT. Suspected veno-occlusive disease developed, however, and hemopoietic recovery was delayed. A bone marrow examination on the 27th day revealed empty marrow with a relative increase in macrophages, and the serum ferritin concentration was extremely high. Impending failure of the graft due to a hemophagocytic syndrome-like condition was strongly suspected, although donor cells were dominant according to a fluorescence in situ hybridization analysis. A second CBT was performed on the 30th day after a preparatory regimen of methylprednisolone and low-dose fludarabine (total dose, 90 mg/m2). Unexpectedly, the the first donor's cells recovered on the fourth day after the second CBT; however, the cells to finally engraft were those of the second donor. This case is informative as an example of rescue management for suspected graft failure.