Current results on the use of imatinib mesylate in patients with relapsed Philadelphia chromosome positive leukemia after allogeneic or syngeneic hematopoietic stem cell transplantation.

Here, we describe a patient diagnosed with chronic myelogenous leukemia who relapsed after matched unrelated donor SCT. The patient was treated with imatinib mesylate and donor lymphocyte infusions, and achieved a complete molecular remission. Additionally, safety and efficacy of imatinib mesylate in a total of 134 patients from 8 centers who underwent allogeneic or syngeneic stem cell transplantation (SCT) and had a relapse of Philadelphia chromosome positive leukemia was reviewed. Data was compiled from abstracts accepted as oral or poster presentations at the ASH (American Society of Hematology) 2001 and EBMT (European Group for Blood and Marrow Transplantation) 2001 & 2002 meetings and additionally literature published on this patient group. Efficacy of imatinib therapy was assessed by morphology, cytogenetic analysis, and determination of donor chimerism. In the evaluable population, hematologic and cytogenetic responses were observed in 66% and 60% of the patients, respectively. Fifty-one of 114 (45%) patients achieved a complete cytogenetic response. No response or progress of disease was noted in 22 out of evaluable 91 patients. The observation period was limited to a maximum of 28 months. A significant improvement in donor chimerism was frequently observed. Only five cases of significant GVHD were reported. Preliminary results show that imatinib mesylate has the potential to positively influence the ratio of donor and recipient cells without inducing a high incidence of severe GVHD. The data suggest that earlier start of imatinib mesylate prior to hematologic relapse in minimum residual disease (MRD) positive patients is a promising treatment concept.

Autologous transplantation of in vivo purged PBSC in CML: comparison of FISH, cytogenetics, and PCR detection of Philadelphia chromosome in leukapheresis products.

To determine the effectiveness of different methods for the detection of tumor cell contamination of collected peripheral stem cells, we performed a study on 39 chronic myelogenous leukemia (CML) patients who were consecutively treated at our department. Analyses of tumor cell contamination by fluorescence in situ hybridization (FISH), conventional cytogenetics, and polymerase chain reaction (PCR) showed marked differences in the percentage of evaluable results: Quantitative analysis of tumor cell contamination was feasible in 60 of 105 (57%) samples evaluated with the use of conventional cytogenetic analysis and in 105 of 107 (98%) samples analyzed by FISH. PCR was evaluable in all 85 samples tested (100%). Both methods were shown to be adequate overall in determining the number of BCR-ABL positive cells, although cytogenetics tended to produce slightly higher percentages. Based on these results, we conclude that FISH performed on leukapheresis products is a rapid and reliable method for assessing the quality of these products and should be used for routine evaluation of tumor cell contamination of CML stem cell products.