Letters and Correspondence
319
“snioldering” CLL ia possible 13.4). It should be stressed. however, that the attempts to define “smoldering” CLL are mainly based o n clinical features such as lymphocyte count, hemoglobin level. lymphocyte doubling time. and bone marrow histology 131. In this context the study by Oscieret al. [Sl is noteworthy in which biological parameters such as cells’ karyotype and immunological phenotype were found to affect disease progression signilicantly. 111 this study we show that myelomunocytic antigens are frequently expressed on B-CLL cells and the presence or absence of these markers correlates with diseaae activity of patients i n early clinical ctage. Forty-seven stage A CLL patients formed the basis ofthis study aimed at investigating the relationship between the expression of myelomonocytic antigens and disease activity. There were 36 men and I I women. The average age was 66 years (SD 8.9). Our patients were further sub-classified as having “smoldering” or live” disease. respectively. The following features defined “smoldering” CLL: stage A . non-diffuse bone marrow hiatology. hemoglobin level 2 13 g/dl. lyiiiphocyte count < 30 x IO”/L. lymphocyte doubling time > I ? months 131. On this basis 28 patients fulfilled criteria of ”smoldering” and I8 of “active” CLL. linmunophenotype studies were performed on peripheral blood cells. In TOSHIHARU ITO all cases lymphocytes exceeded 5 X IO’iL and more than 7 5 4 cells were YASURO MIVAIRI CD5 and CD19 positive. Studies of myelomonocytic antigens were perTETSUO KUWABARA formed in 3 I patients at presentation and s u b q u e n t l y in the remaining I h KAZUO DAN patients (while still in stage A). The following myelomonocytic monoTAKEO NOMURAclonal antibodies were used in indirect fluorescence: CDI Ib (OK-MI). Third Depadment of Internal Medicine, Nippon Medical School, CD13 (OK-Ml3). CD14 (OK-M14). CD33 (MY9). CD36 (OK-MS). FluTokyo, Japan orescence reading was performed by using a CYTORON cytofluorograph (Ortho Diagnostic System) flow cytometry. Tu determine whether lymREFERENCES phoid and myeloid antigens wet-e expressed on the same cells double-label I. Tubahio T. Kurata Y . Yimezawa T, Kitani 1’:Quantification of platclot-arwciated immunofluorescence WBE performed in several patients by using phycoeriIgG with coinpctitivc wlid-phue cnrynie immunoassay. Acta Hdeinalol (Bascl) trin (PE)-conjugated (OK-B7) (CD21) and FTIC-conjugated MY9 (CD33). 66:251, I981 OK-MI3 (CD13). OK-M14(CD14). respectively. 2 . Furuaawa S: Autoinimunc neuiropenia Acta Hacnratol Jpn 4X. 1753. 19x5. The frequencies of marker expression analyzed as a function of disease 3. H u m b e r g BPC. Van Lccuwen M A , Van Rijswijk MH. Stern AC. Vellenga E. activity are depicted in Table 1. As shown, higher CD13 and CD33 expresCnrrcclion of granulocyiopcnia in Fclty’\ ayndmmc hy Eranulocyte-macrophage sion was associated with ”active” disease. colony-stimulating factor Sirnultaneotir induction o l interleukin-6 release and Such an association raises important questions about the natural history tlare-up ofthe arthritis. Blood 74.2769, 1Y89. of CLL. I n this context our results might therefore suggest that clinical disease progression to an active phase is manifested by the expression oC mqclomonocytic antigens. Furthermore, such a feature might imply a close relationship between B-lymphoid and myelomonocytic lineages of differentiation. In addition, “in citro” studies seem to support the view that the expression of niyelomonocytic antigens might be a feature of B-cell activation [ 61. Myelomonocytic Associated Antigens in Early B-Chronic Although the number of patients included in this study is small 10 draw Lymphocytic Leukemia Correlate With firm conclusions. the inmunophenotypic analysis, including myelomonoDisease Activity cytic markers. becomes a useful tool to disclose subgroups of CLL patients To the Editor: The expression u l myelomonocytic antigens is a phcnome- in early phase of disease with different prognoses. non occurring with a definite frequency in B-chronic lyniphocytic leukemia (B-CLL). As far as its clinical implication is concerned, such a finding ha5 STEFANO MOLICA been associated with features influencing the behaviour of disease such as a Divisione di €matologia, Ospedale Regionale, “A. Pugliese”, diffuse hone marrow histology and a short lymphocyte doubling time [ I .?I. Cafanzaro, M y However, studies dealing with myelomonocytic antigens in early B-CLL are virtually absent. REFERENCES For the large majority of patients with early B-CLL (Binet’s stage A or Rai’s stage 0 or I ) no staging system is able to predict those who will I . Pinto A . Vcl Vecchio L. Cai-hone A . el iil Exprrsaion of tnycluiiionr,cyiic milremain at the same clinical stage. Recent studies suggest that a definition 0 1 gens i?. aawclated with unfavorable clinicopr In B-cell chronic peak level 0 1 14.5 x 10y/L on the 20th day. when rG-CSF had to be discontinued because of the appearance of exanthema on both legs. which was regarded as an allergic reaction to rC-CSF. After discontinuation of the G C S F therapy the neutrophil count returned to the pretreatment level within a week. and the exanthema disappeared. No noteworthy side effects other than the skin eruption were noted. Subsequently. two courses of bolus methyl-prednisolone (mPSL) therapy were given resulting in a gradual increase in the neutrophil count to a level of 2 X IO’iL. During the maintenance therapy with prednisolone. pneumonia developed and the patient died of respiratory failure. It has been reported that rGM-CSF could correct the neutropenia in FS. but side effecta such a h fever and flare-up of the arthritis were observed 131. On the other hand. to our knowledge, there have been no reports ofrG-CSF in treating patients with FS. The mechanism ofthe effects of rC-CSF in this case is unclear. but there is a posaibility that excess production of neutrophils by rC-CSF might outweigh the destruction of IgG-bound neutrophik in the peripheral blood. Further clinicid study is required to evaluate the long-term effects of rG-CSF and to determine its optimum dosages for initial and maintenance therapies.
’
TABLE 1. Myelomonocytic Associated Antigens in Stage A Chronic Lymphocytic Leukemia’ Diseaw \talus
__~
~
Smoldering C L L (mean 5 SD) Active CLL (mean z SD) t’.\,illuc
*NS
=
not >igiiificanl
CD13 _ _ _ _ _
C D I Ib
5.59 6X.3
?
2
NS
3S.6 3S.X
38.6 -t 3 S . I 61.2 27.5
319
“snioldering” CLL ia possible 13.4). It should be stressed. however, that the attempts to define “smoldering” CLL are mainly based o n clinical features such as lymphocyte count, hemoglobin level. lymphocyte doubling time. and bone marrow histology 131. In this context the study by Oscieret al. [Sl is noteworthy in which biological parameters such as cells’ karyotype and immunological phenotype were found to affect disease progression signilicantly. 111 this study we show that myelomunocytic antigens are frequently expressed on B-CLL cells and the presence or absence of these markers correlates with diseaae activity of patients i n early clinical ctage. Forty-seven stage A CLL patients formed the basis ofthis study aimed at investigating the relationship between the expression of myelomonocytic antigens and disease activity. There were 36 men and I I women. The average age was 66 years (SD 8.9). Our patients were further sub-classified as having “smoldering” or live” disease. respectively. The following features defined “smoldering” CLL: stage A . non-diffuse bone marrow hiatology. hemoglobin level 2 13 g/dl. lyiiiphocyte count < 30 x IO”/L. lymphocyte doubling time > I ? months 131. On this basis 28 patients fulfilled criteria of ”smoldering” and I8 of “active” CLL. linmunophenotype studies were performed on peripheral blood cells. In TOSHIHARU ITO all cases lymphocytes exceeded 5 X IO’iL and more than 7 5 4 cells were YASURO MIVAIRI CD5 and CD19 positive. Studies of myelomonocytic antigens were perTETSUO KUWABARA formed in 3 I patients at presentation and s u b q u e n t l y in the remaining I h KAZUO DAN patients (while still in stage A). The following myelomonocytic monoTAKEO NOMURAclonal antibodies were used in indirect fluorescence: CDI Ib (OK-MI). Third Depadment of Internal Medicine, Nippon Medical School, CD13 (OK-Ml3). CD14 (OK-M14). CD33 (MY9). CD36 (OK-MS). FluTokyo, Japan orescence reading was performed by using a CYTORON cytofluorograph (Ortho Diagnostic System) flow cytometry. Tu determine whether lymREFERENCES phoid and myeloid antigens wet-e expressed on the same cells double-label I. Tubahio T. Kurata Y . Yimezawa T, Kitani 1’:Quantification of platclot-arwciated immunofluorescence WBE performed in several patients by using phycoeriIgG with coinpctitivc wlid-phue cnrynie immunoassay. Acta Hdeinalol (Bascl) trin (PE)-conjugated (OK-B7) (CD21) and FTIC-conjugated MY9 (CD33). 66:251, I981 OK-MI3 (CD13). OK-M14(CD14). respectively. 2 . Furuaawa S: Autoinimunc neuiropenia Acta Hacnratol Jpn 4X. 1753. 19x5. The frequencies of marker expression analyzed as a function of disease 3. H u m b e r g BPC. Van Lccuwen M A , Van Rijswijk MH. Stern AC. Vellenga E. activity are depicted in Table 1. As shown, higher CD13 and CD33 expresCnrrcclion of granulocyiopcnia in Fclty’\ ayndmmc hy Eranulocyte-macrophage sion was associated with ”active” disease. colony-stimulating factor Sirnultaneotir induction o l interleukin-6 release and Such an association raises important questions about the natural history tlare-up ofthe arthritis. Blood 74.2769, 1Y89. of CLL. I n this context our results might therefore suggest that clinical disease progression to an active phase is manifested by the expression oC mqclomonocytic antigens. Furthermore, such a feature might imply a close relationship between B-lymphoid and myelomonocytic lineages of differentiation. In addition, “in citro” studies seem to support the view that the expression of niyelomonocytic antigens might be a feature of B-cell activation [ 61. Myelomonocytic Associated Antigens in Early B-Chronic Although the number of patients included in this study is small 10 draw Lymphocytic Leukemia Correlate With firm conclusions. the inmunophenotypic analysis, including myelomonoDisease Activity cytic markers. becomes a useful tool to disclose subgroups of CLL patients To the Editor: The expression u l myelomonocytic antigens is a phcnome- in early phase of disease with different prognoses. non occurring with a definite frequency in B-chronic lyniphocytic leukemia (B-CLL). As far as its clinical implication is concerned, such a finding ha5 STEFANO MOLICA been associated with features influencing the behaviour of disease such as a Divisione di €matologia, Ospedale Regionale, “A. Pugliese”, diffuse hone marrow histology and a short lymphocyte doubling time [ I .?I. Cafanzaro, M y However, studies dealing with myelomonocytic antigens in early B-CLL are virtually absent. REFERENCES For the large majority of patients with early B-CLL (Binet’s stage A or Rai’s stage 0 or I ) no staging system is able to predict those who will I . Pinto A . Vcl Vecchio L. Cai-hone A . el iil Exprrsaion of tnycluiiionr,cyiic milremain at the same clinical stage. Recent studies suggest that a definition 0 1 gens i?. aawclated with unfavorable clinicopr In B-cell chronic peak level 0 1 14.5 x 10y/L on the 20th day. when rG-CSF had to be discontinued because of the appearance of exanthema on both legs. which was regarded as an allergic reaction to rC-CSF. After discontinuation of the G C S F therapy the neutrophil count returned to the pretreatment level within a week. and the exanthema disappeared. No noteworthy side effects other than the skin eruption were noted. Subsequently. two courses of bolus methyl-prednisolone (mPSL) therapy were given resulting in a gradual increase in the neutrophil count to a level of 2 X IO’iL. During the maintenance therapy with prednisolone. pneumonia developed and the patient died of respiratory failure. It has been reported that rGM-CSF could correct the neutropenia in FS. but side effecta such a h fever and flare-up of the arthritis were observed 131. On the other hand. to our knowledge, there have been no reports ofrG-CSF in treating patients with FS. The mechanism ofthe effects of rC-CSF in this case is unclear. but there is a posaibility that excess production of neutrophils by rC-CSF might outweigh the destruction of IgG-bound neutrophik in the peripheral blood. Further clinicid study is required to evaluate the long-term effects of rG-CSF and to determine its optimum dosages for initial and maintenance therapies.
’
TABLE 1. Myelomonocytic Associated Antigens in Stage A Chronic Lymphocytic Leukemia’ Diseaw \talus
__~
~
Smoldering C L L (mean 5 SD) Active CLL (mean z SD) t’.\,illuc
*NS
=
not >igiiificanl
CD13 _ _ _ _ _
C D I Ib
5.59 6X.3
?
2
NS
3S.6 3S.X
38.6 -t 3 S . I 61.2 27.5
