Prognostic impact of bone marrow erythropoietic precursor cells and myelofibrosis at diagnosis of Ph¹⁺ chronic myelogenous leukaemia – a multicentre study on 495 patients

Abstract

A multicentre clinicopathological study was performed on 495 patients with chronic‐phase Ph1+ chronic myelogenous leukaemia (CML) to determine bone marrow characteristics that exert a significant impact on survival under standard treatment regimens. Immunohistochemical and morphometric techniques were applied to identify nucleated erythroid precursor cells in the bone marrow and to quantify argyrophilic fibre density. Application of the Sokal index and another recently proposed CML score failed to distinguish three clearly defined risk groups. A borderline increase in fibre content (i.e. doubling of the normal density) and a relevant reduction of medullary erythropoiesis proved to be important predictors for survival, even in low‐risk classified patients, according to both clinical scores. With regard to optimal treatment strategies, patients with manifest myelofibrosis showed no significant difference in survival rates under interferon or hydroxyurea treatment. Multivariate analysis confirmed the prognostic value of histological features. A risk model based on three variables (fibre density, erythropoietic precursors and spleen size) was constructed that enabled a distinct discrimination of risk profiles. In conclusion, the presented data provide compelling evidence that bone marrow features at diagnosis exert a significant impact on prognosis in CML. In this context, the generally clinical‐based multivariate risk classification can be improved by consideration of morphological variables that are acting independently of treatment modalities.

Leukemic spleen cells are more potent than bone marrow-derived cells in a transgenic mouse model of CML

“…The propensity for erythrocytic differentiation was also described in Bcr --Abl transduced murine BM as well as human cord blood cells. 26,27 At the same time, erythropoiesis was decreased in the BM in our Bcr --Abl positive mice, and this has been described for human CML as well 28 where both decreased BM erythropoiesis and increased spleen size are adverse prognostic factors. In addition, we observed an increased leukemic potential upon induction of Bcr --Abl expression in spleen cells before transplantation or transplantation of pre-induced spleen LSK cells combined with BM non-LSK cells compared with pre-induced BM LSK cells combined with spleen non-LSK cells.…”

Clinical and Hematological Features of 335 Patients of Chronic Myelogenous Leukemia Diagnosed at Single Centre in Northern Pakistan

“…The diagnosis of CML was confirmed either by cytogenetic analysis for Philadelphia chromosome or RT-PCR based BCR-ABL analysis (Applied Biosystems 7500 Real time PCR system). 9 Diagnosis of accelerated phase of CML was based on one or more of the following criteria: 10,11 (1) rising white cell count and/or splenomegaly despite chemotherapy, (2) thrombocytosis > 1000 x 10 9 /L despite treatment, (3) persistent thrombocytopenia not related to chemotherapy, (4) > 20% basophils in peripheral blood, (5) 10%-19% blasts in blood or bone marrow, and (6) bone marrow fibrosis with presence of megakaryocyte clusters. Blast crisis was diagnosed when there were >20% blasts in the bone marrow.…”

Classification of myeloid neoplasms: a comparative review

“…61 A study of 495 CML patients determined that increased marrow fibrosis and decreased erythropoiesis are additional predictors of a poor prognosis, regardless of therapy. 64 Chronic neutrophilic leukemia. Other granulocytic forms of MPD are morphologically, genetically, and clinically distinct from CML.…”