Periodic morphologic, cytogenetic and clonality evaluation after autologous peripheral blood progenitor cell transplantation in patients with lymphoproliferative malignancies

Abstract

Background and objectives: Myelodysplastic syndrome (MDS), secondary acute myeloid leukemia (sAML) and clonal karyotypic abnormalities, have been recognized as relatively frequent and potentially serious complications of autologous peripheral blood progenitor cell transplantation (PBPCT) for Hodgkin's disease (HD), non-Hodgkin's lymphoma (NHL) or multiple myeloma (MM).

Design and methods: We analyzed 66 patients, undergoing PBPCT for HD, NHL, MM or chronic lymphocytic leukemia (CLL). Patients reported in this study had to be in continuous complete remission after transplantation without receiving chemo-radiotherapy or other biological response modifiers, had to show absence of cytogenetic abnormalities and myelodysplastic features at transplantation and had to have at least 12 months of follow-up. We evaluated the bone marrow, peripheral blood, cytogenetics and clonality (HUMARA) 12 months after the transplant and thereafter every 12 months or every 6 months if lineage dysplasia, clonal or cytogenetic abnormalities were detected.

Results: We did not observe MDS/sAML, according to the FAB classification, in 163 assessments of 66 patients over a median follow-up of 25 months (range 12-106) after PBPCT. Twelve patients showed lineage dysplasia: six patients had dyserythropoiesis, 2 patients dysgranulopoiesis, one dysmegakaryocytopoiesis, two patients showed double lineage dysplasia (erythroid and granulocytic), and one patient showed dysgranulopoiesis at the first control acquiring dyserythropoiesis at the next follow-up. We found three cytogenetic abnormalities in the absence of concomitant dysplastic features: transient -5q, -Y, fra(10)(q25). The female patient with the cytogenetic abnormality -5q showed transient unbalanced clonality by HUMARA assay; further controls documented normalization of both clonality and cytogenetics.

Interpretation and conclusions: The occurrence of MDS/sAML depends on a variety of risk factors such as the number and type of prior courses of chemo-radiotherapy, total body irradiation in conditioning regimen, cytogenetic and morphologic alterations prior to transplant. This may account for the difference in reporting MDS/sAML after transplantation. The lack of exposure to recognized risk factors for MDS/sAML in our patients may account for the absence of this complication in this study. We consider that the use of stringent morphologic criteria, especially during the first period after PBPCT, combined with cytogenetic, clonality and FISH analyses are necessary for a correct diagnosis of MDS and to overcome the limitations of the FAB and WHO classifications in this setting.