[CANCER RESEARCH 43, 905-912, February 1983] 0008-5472/83/0043-0000502.00 Cytogenetic Studies and Clinical Aspects of Patients with Plasma Cell Leukemia and Leukemic Macroglobulinemia 1 Yoshimi Ueshima, 2 Shirou Fukuhara, Kenichi Nagai, Kiyoshi Takatsuki, and Haruto Uchino First Division, Department of Internal Medicine, Faculty of Medicine, Kyoto University, 54-Shogoin Kawaramachi, Sakyo-ku, Kyoto 606 [Y. U., S. F., K. N., H. U.], and Second Division, Department of Internal Medicine, Faculty of Medicine, Kumamoto University, Kumamoto [K. T.], Japan ABSTRACT evolution of myeloma cells (1 6). This assumption remains ten- tative because of lack of data in PCL. Chromosomes of six patients with plasma cell leukemia and We, rc, nnrt fh~ nhrnmns s163 ~ncl fh# r:linir~l ~ncl one patient with leukemic macroglobulinemia were examined ..... r .................................................. morphological features in 6 patients with PCL and in one from peripheral blood, bone marrow, and/or pleural fluid. All patient with leukemic MG. The karyotypic differences between the patients had a clonal chromosomal abnormality. The modal these patients and reported cases of leukemias, malignant chromosome number was near tetraploid in two, pseudodiploid lymphomas, and MM are discussed. in two, and hypodiploid in three patients. Rearrangements of chromosome 1 were found in all the patients. The most con- sistent abnormality was a large marker involving the long arm MATERIALS AND METHODS of No. 1, found in six patients, including the patient with Chromosomes of 6 patients with PCL and one patient with leukemic macroglobulinemia. Each patient had one to four large markers MG were examined from peripheral blood, bone marrow, and/or which resulted in partial trisomy to hexasomy for the long arm pleural effusion specimens. PCL was defined as more than 0.5 x 109 of No. 1. The translocations occurred with No. 9 in two, with circulating plasma cells or plasmoblasts per liter. The peripheral blood No. 1 6 in two, and Nos. 8, 1 7, and 1 8 each in one patient. The mononuclear cells were separated with Ficoll-sodium metrizoate gra- survival time from the diagnosis was less than 1 year in five of dient centrifugation and were cultured in Roswell Park Memorial Insti- them and over 2 years in one. The only patient whose cells tute Medium 1640 containing 10% fetal calf serum at 37 ~ for 24 to 48 lacked an extra lq lived for over 3 years. Five 14q+ marker hr in 5% CO2. Bone marrow and pleural fluid samples were processed directly without prior culture. Mitotic cells were arrested with 1 x 10 -6 chromosomes were detected in three patients. The donor chro- M colchicine for 2 hr, treated with 0.075 M KCI for 10 to 30 min, and mosome was No. 1 1 in one of these and was undetermined in subsequently fixed in methanol:acetic acid (3:1). Air-dried slides were the others; the size of each 14q+ marker seemed quite differ- first stained with Giemsa and then photographed; after destaining, the ent which suggested different donor chromosomes. Loss of a same cells were restained with quinacrine mustard and photographed sex chromosome was found in five patients. Loss of No. 13 with a fluorescence microscope. Case 1 was banded with a G-banding and gain of No. 7 or 7q were each found in two patients. method (21). Descriptions of the chromosomes follow the recommen- Rearrangement or deletion of the short arm of No. 8 was found dations of the ISCN (1978) (9). in five patients. A rearrangement of 9p was found in three patients. The myeloma cells had a different morphology in the peripheral blood, bone marrow, and/or pleural fluid before and RESULTS after the leukemic phase of one patient; however, chromosome Clinical data on the 7 patients are presented in Table 1. Four analysis revealed the same clone despite the altered morphol- patients had PCL at the time of initial diagnosis, and in 2 ogy. patients (Cases 1 and 5) a leukemic phase subsequently de- veloped. The patient with MG (Case 7) also had leukemic INTRODUCTION plasmacytoid cells at diagnosis. The survival after diagnosis was less than 1 year in 5 patients and over 2 years in 2. All the PCL 3 is an infrequent phase in MM. The clinical course may patients had anemia, hypercalcemia, and renal insufficiency. be fulminant with features resembling those of acute leukemia, Three had hepatosplenomegaly (Cases 1, 2, and 5), and 3 and it is sometimes recognized as a distinct subentity (28). (Cases 2, 5, and 6) had pleural effusion with plasma cell Chromosome studies in patients with MM and related parapro- invasion. In addition, one had progressive lower limb paresis teinemic disorders have often been reported (1,3, 1 0, 1 1, 1 5, (Case 2), one had meningeal involvement (Case 5), and another 16, 22, 23, 26, 29), but there are few reports of PCL (8, 1 1, had obstructive jaundice with plasma cell invasion (Case 6). 16, 26). In MM, the pattern of chromosome aberrations has Postmortem examination in 3 patients (Cases 1, 2, and 5) b,~en quite variable, and no consistent markers were noted in showed very extensive infiltration of the marrow, liver, lymph the published data. On the other hand, it has been suggested nodes, lungs, and other organs with plasma cells. that the 14q+ marker may be necessary for the leukemic Cytogenetic data are presented in Table 2. Chromosomes were studied before treatment in 2 patients, after treatment in Supported in part by a grant from the Ministry of Welfare of Japan. 4 patients, and before and after treatment in one patient. There 2 To whom requests for reprints should be addressed, at M.D. Department of were no clear differences between the karyotypes of untreated Internal Medicine, Faculty of Medicine, Kyoto University, 54-Shogoin Kawara- machi, Sakyoku, Kyoto 606, Japan. Present address: M.D. Department of Med- patients and those of treated patients. All of the patients had a icine, Box 420, University of Chicago, Chicago, II1. 60637. clonal chromosomal abnormality. In 2 patients (Cases 1 and The abbreviations used are: PCL, plasma cell leukemia; MM, multiple mye- Ioma; MG, macroglobulinemia. 2), the cells from bone marrow, peripheral blood, and/or Received June 17, 1982; accepted October 11, 1982. pleural effusion had the same karyotype. In another patient FEBRUARY1983 905 Downloaded from cancerres.aacrjournals.org on September 24, 2021. © 1983 American Association for Cancer Research. Y. Ueshima et al. Table 1 Clinical and hematological data in 6 patients with PCL and a patient with MG at diagnosis of PCL % of plasma cells WBC in pe- and atypical lym- Therapy before Survival after Age Serum para- ripheral blood phocytes in periph- chromosome ex- Total duration of chromosome ex- Case a Sex (yr) protein (x 109/liter) eral blood amination disease (mos.) amination (mos.) 1 (M. Y.) M 45 Absent 52.1 90 M, b P 39 2 2 (Y. N.) M 35 IgG~ 7.6 33 E, P 10 7 3 (S. I.) F 71 IgG• 9.7 72 None 1 1 4 iT. Y.) M 73 BJ~ 20.7 10 None 1.5 1.5 5 (N. Y.) M 45 IgGX 8.2 37 (1) None 8 (1) 8 (2) M, P (2) 4 (3) 0 6 (S. K.) F 64 IgAK 6.4 22 M, P 34 (1),31 (2) 2 7 (M. H.) M 71 IgMX 78.0 90. D, C, 6-MP, P 12 8 a Cases 1 to 6, PCL; Case 7, MG. b M, melphalan; P, prednisone; E, endoxan; D, daunomycin; C, 1-/~-D-arabinoside furanosylcytosine; 6-MP, 6-mercaptopurine. Table 2 Chromosome patterns of patients with PCL and MG Date of chro- No. of cells ex- % of cells with Source of mosome stud- amined abnormal kary- Patient sample ies (banded) otype Modal karyotype 1 (M. Y.) BM a 9/21/77 20 100 44,X,-Y,-21,-22,1p-,+1q-,t(11 ;14)(ql 1 ;q32),14q+ PB 10/15/77 19 1 O0 44,X,-Y,-21,-22,1 p-, + 1q-,t(11 ;14)(ql 1 ;q32), 14q+ 2 (Y. N.) BM 4/12/79 16 100 44,X,-Y,-9,- 13,t(6;8)(q 13;pl 1 ), + der(9)t(1 ;9)(1 qter--> 1 ql 2::1 q44--* 1 ql 2: :9q34--> 9pter) PB 4/12/79 9 100 44,X,-Y,-9,- 13,t(6;8)(q 13;pl 1 ), + der(9)t(1 ;9) PE 4/12/79 7 86 44,X,-Y,-9,-13,t(6;8)(q 13;pl 1 ), + der(9)t(1 ;9) 3 (S. I.) PB 10/25/79 40 20 43,X,-X,- 1,-8,-9,- 1 O,- 13,- 22, + der(8)t(1 ;8)(1 qter---*cen--,8qter), +der(9)t(1 ;9)(1 qter--* 1q21 ::9p24--*9qter), + der(10)t(1 ;10) (10pter-* 10q26:: 1 p31--* 1 pter), + t(1 ; ?)(q 12;?) 4(T. Y.) PB 12/26/79 38 76 78,XX,-Y, +4,+5,+7,+ 7,+ 7,+7, +8, +8,+ 10,+ 12, + 12, + 16,+ 18,+ 19,+ 19,+21, +21,+3q+,+3q+,+3p-,+9p+,+9p+,+11p+,+11p+,+14q+,+14q+, + 1 6p +, + 16p+, + del(1 )(q21 ), + del(1 )(q21 ), + der(17)t(1 ; 17) (1 qter--->1 ql 2::17pl 3-,17qter), + der(17)t(1 ;17) 5 (N. u BM 1/12/80 14 85 46,XY,- 16,- 18,del(6)(q21 ), + der(16)t(1 ;16)(1 qter-* 1 q21 :: 16pl 3--->16qter), + marl PB 5/21/80 16 100 46,XY, - 16, - 18,del(6)(q21 ), + der(16)t(1 ;16), + marl PE 9/06/80 20 100 47,XY,-8,- 15,- 16,- 18,del(6)(q21 ), + der(16)t(1 ;16), + t(8; 15)(8qter--*8p23::15ql 2 --,15qter),14q+,+mar1 ,+mar2,+mar3/sdl (4 cells)47,XY, same, 4q+ 6(S.