Blut (1988) 57:19-23 Blut © Springer-Verlag 1988 Bone marrow histopathologic patterns and immunologic phenotype in B-cell chronic lymphocytic leukaemia Alberto Orfao 1, Marcos Gonzalez 1, Jesus San MigueP, Agustin Rios 1, Maria Dolores Caballero 2, Miguel Sanz 3, Maria Jose Caimuntia 4, Purificaci6n Galindo 5, and Antonio Lopez Borrasca 1 1 Servicio de Hematologia, Hospital Clinico Universitario, E-37007 Salamanca, Spain 2 Servicio de Hematologia, Hospital Virgen Blanca, E-34002 Palencia Leon, Spain 3 Servicio de Hematologia, RSSS Palencia, E-24010, Spain 4 Servicio de Hematologia, Hospital General, E-40044 Segovia, Spain 5 Unidad Docente de Bioestadistica, Facultad de Medicina, Universidad de Salamanca, E-37007 Salamanca, Spain Summary. The present work analyzes the clinico- biological and immunological characteristics - the latter hitherto unexplored - of the different bone marrow histopathological patterns of the B-cell chronic lymphocytic leukaemia (B-CLL). In addi- tion, we studied whether any or some of these para- meters were able to predict the probability of a par- ticular pattern of bone marrow involvement ap- pearing. Of the 100 B-CLL cases studied 41 had a diffuse pattern and 59 were non-diffuse - intersti- tial 27, nodular 11 and mixed 21 -. Neither clinical nor immunological differences were observed among the distinct non-diffuse patterns. The patients in the diffuse group displayed an increased incidence of/~+ isotype and a higher proportion of HLA-DR and HAN-PC 1 positive cells while, conversely, re- activity with the FMC 8 McAb was lower. In addi- tion, patients with a diffuse pattern of BM involve- ment displayed features of a more extensive disease: a higher incidence of adenopathies (p < 0.05), hepatomegaly (p < 0.01), splenomegaly (p < 0.01), anaemia (p < 0.01) and thrombopenia (p < 0.01) as well as higher levels of peripheral blood lympho- cytosis (p < 0.05) and a higher percentage of BM lymphocytic infiltration (p < 0.001). Multiple re- gression analysis showed that thrombopenia and splenomegaly were the two most important features in predicting the probability of a diffuse pattern. Key words: B-CLL - Bone marrow histopathology - Immunophenotype Introduction Different bone marrow (BM) histopathological pat- terns have been recognized in B-cell chronic lyre- Offprint requests to: A. Orfao phocytic leukaemia (B-CLL) and it is clearly dem- onstrated that they have prognostic value [2, 5, 6, 10, 11,22]. In addition, recently the Spanish Co- operative group for B-CLL study has shown that the histopathological pattern of BM infiltration is a better single prognostic parameter than any of the variables employed in current clinical staging sys- tems [23]. However, whether or not these histo- pathological patterns are associated with a partic- ular immunological phenotype of B-CLL cells has not previously been analyzed in detail [16]. In order to gain further knowledge about this possibility we studied the immunological pheno- type as well as the clinico-biological features of 100 B-CLL patients. Another aim of our work was to establish whether the clinico-biological and immu- nological characteristics at presentation can predict the BM histopathological patterns. Material and methods Patients: One hundred patients (71 males and 29 females) diag- nosed with B-CLL according to both Rai's criteria [19] and im- munological markers, were included in the study. The patients were classified into four different BM histopathological pat- terns [11]: interstitial, nodular, mixed and diffuse. The B-CLL cases were also grouped according to the Rai staging [19] and the International Workshop staging [4]. The BM biopsy, the clinico-biological study and assessment of the immunological phenotype were performed in all cases at the moment of diag- nosis, prior to chemotherapeutic treatment. The clinical and haematological data analyzed included: age, sex, the reason for consulting, presence of lymphadenopathies, splenomegaly, hepatomegaly, extralymphatic infiltration, anaemia ( < 10 g of hemoglobin/dl), thrombopenia ( < 100×109 platelets/1), the peripheral blood (PB) lymphocyte count and the percentage of lymphatic infiltration in the BM aspirate. Immunological studies." Mononuclear cells from PB were ob- tained by Ficoll-hypaque (Pharmacia Fine Chemicals) density gradient centrifugation and tested for: a) spontaneous rosette- forming cells with AET-treated sheep erythrocytes (SRFC); b) spontaneous rosette-forming cells with mouse erythrocytes (MRFC); c) surface immunoglobulins (sIg) were detected by