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Summary:chronic myeloid leukemia (CML) relapsed after allogeneic bone marrow transplantation (BMT). [1][2][3][4][5] Chimerism studies in patients who relapsed following an Recent observations of chimerism in patients relapsed following an allotransplant suggest the persistence of allotransplant suggest the persistence of immunotolerance thus offering a biologic rationale for the use of DLT. 6 Sevimmunotolerance, thus offering a biologic rationale for the use of donor lymphocyte transfusion (DLT). In this eral methods with different sensitivities are useful to evaluate the chimerism status in transplanted patients. These study, we have analyzed by PCR amplification of several VNTR regions, sequential bone marrow and peripheral include cytogenetics, Y body detection, protein polymorphism, and red cell phenotyping. 7-9 More recently, DNAblood DNA samples in four patients who received DLT for CML relapse after bone marrow transplantation.based methodology has provided more sensitive techniques. In particular, polymerase chain reaction (PCR) amplifiPrior to DLT, all patients showed mixed chimerism in peripheral blood cells while two had mixed chimerism cation of individual specific genetic loci, such as the variable tandem repeats (VNTR) and the short tandem repeats and two no chimerism in the BM. None of these four patients showed evidence of chimerism at the cyto-(STR), have increased the sensitivity of the analysis up to 1-0.1% and 0.1-0.01%, respectively. 10,11 Using these genetic level (all had 100% +ve metaphases). After DLT, a complete hematologic and molecular remission (ie disassays, a condition of mixed chimerism (MC) has been shown in 80% of CML patients receiving T cell-depleted appearance of the BCR/ABL fusion transcript) was obtained in the two patients who had bone marrow allografts. 11 With regard to CML patients treated with DLT for mixed chimerism prior to DLT. The two patients without evidence of marrow chimerism prior to DLT conrelapse after BMT, Mackinnon et al 12 have analyzed the chimerism status of T lymphocytes by PCR and shown that verted to a pattern of mixed chimerism after DLT, but both developed a severe bone marrow aplasia occurring a MC was present in almost every patient prior to DLT. While this observation encourages the use of adoptive at day 56 and 36, respectively. With regard to the sequential analysis of bone marrow chimerism after immunotherapy in these patients, it provides no prognostic information on the post-DLT clinical outcome. DLT we observed that: (1) the disappearance of BCR/ABL +ve cells paralleled the conversion to a patIn this study, we have analyzed by PCR amplification of several VNTR regions sequential bone marrow and periphtern of full donor chimerism; and (2) the time interval to achieve CR was inversely correlated with the percenteral blood DNA samples in four patients who received DLT for CML relapse after BMT. We show that bone marrow age of donor DNA in bone marrow. In conclusion, we have shown here that the assessment of bone marrow chimerism pre-DLT is pr...

We report the clinical, hematologic, cytogenetic, and molecular characteristics of 13 patients with Philadelphia-negative (Ph-), bcr-negative atypical chronic myelogenous leukemia (CML). In the majority of cases, the phenotypic features at presentation resembled those of typical CML. However, these patients presented with a higher median age, lower median hemoglobin levels, and lower leukocyte and platelet counts than patients with Ph-positive CML. Cytogenetic analysis showed an abnormal karyotype in only one case. Southern blot investigation, using probes exploring the entire M-bcr region, demonstrated the absence of genomic bcr-abl rearrangements. The assessment of clonality in five patients (study of X-methylation patterns in females heterozygous at the DXS255 locus) indicated the proliferation of a monoclonal cell population. Disease evolution was mostly characterized by bone marrow failure, extramedullary infiltrates, and poor response to chemotherapy, without evidence of overt acute transformation. Our observations suggest that some hematologic and clinical features and the modalities of disease progression are presently the most helpful factors in distinguishing these bcr/abl-negative patients from those with typical bcr+CML. The differences existing also with chronic myelomonocytic leukemia (CMMoL), allow the consideration of ph-/bcr- CML as a separate entity, the nature of which remains to be elucidated.

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