LETTERS TO THE EDITOR A Case of Chronic Myelogenous Leukemia with Four Philadelphia Chromosomes Kovacs et al. recently described a patient in the blastic phase of chronic myelogenous leukemia (CML) with three isodicentric Philadelphia chromosomes; i.e., with as many as six copies of the rearranged region of chromosome #22 per cell [1]. Such an extreme increase in the number of copies of the Ph chromosome is very rare in CML, even though the appearance of the second Ph is one of the most com- mon changes accompanying blastic phase of the disease. We have recently exam- ined a very similar patient with CML who at the onset of blastic phase developed a complex hypotriploid karyotype with four copies of the Ph chromosome in the stemline cells. The patient was a 59-year-old white female whose diagnosis of Ph- positive CML was made in November 1980. She presented with splenomegaly and WBC of 100,000 with 40% mature granulocytes, 22% metamyelocytes, 17% myelo- cytes, 10% promyelocytes, 5% blasts, and 6% lymphocytes. The initial treatment with busulfan resulted in a rapid decrease of the leukocytes and splenomegaly. She remained in the chronic phase of CML over the next 5 years requiring treatment with busulfan on four occasions for fever and splenomegaly. In January 1986 the patient developed fever and splenomegaly, and the WBC increased to 22,000 with 22% blast cells. The bone marrow showed replacement of normal elements with myeloblasts consistent with CML in accelerated phase. Cytogenetic analysis of the bone marrow aspirate showed a modal karyotype 59,XX, + 6, + 6, + 8, - 10, + 11, + 12, + 19, + 19, + 20, - 21, - 22, + 2[del(10)(q11.2),2] t(10;21)(q11.2;q22)+4Ph. Forty-one percent of the cells showed four Ph chromosomes with the remaining containing from one to three copies of the Ph. The patient received a course of chemotherapy consisting of daunomycin, cyto- sine arabinoside, vincristine, and prednisone, which resulted in a partial clinical remission after 4 weeks. This correlated with the decline in the percentage of cells carrying multiple copies of the Ph chromosome from 87% to 25% on January 30, 1986. Two weeks later, however, the percentage of cells with multiple copies of Ph chromosome increased to 50% and the patient relapsed clinically, shortly thereafter (Table 1). The second course of chemotherapy resulted, again, in partial remission. The patient died in June 1986. The unusual increase in the number of copies of the Ph chromosome in our case is very similar to that described by Kovacs et al. [1]. In addition, we were able to positively correlate the clinical course of the disease with the proportion of cells in the bone marrow carrying multiple copies of the Ph chromosome. LONGINA GIBAS LAIRD JACKSON Division of Medical Genetics Thomas Jefferson University Philadelphia, PA 10107 FREDERICK M. FELLIN Cardeza Foundation for Hematologic Research Thomas Jefferson University Philadelphia, PA 10107 Received September 29, 1986; accepted October 8, 1986. 179 ~© 1987 Elsevier Science Publishing Co., Inc. Cancer Genet Cytogenet 28:179-180(1987) 52 Vanderbilt Ave., New York, NY 10017 0165-4608/87/$03.50

A case of chronic myelogenous leukemia with four Philadelphia chromosomes

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LETTERS TO THE EDITOR

A Case of Chronic Myelogenous Leukemia with Four Philadelphia Chromosomes

Kovacs et al. recent ly descr ibed a pat ient in the blastic phase of chronic myelogenous leukemia (CML) with three isodicentr ic Ph i lade lph ia chromosomes; i.e., with as many as six copies of the rearranged region of chromosome #22 per cell [1]. Such an extreme increase in the number of copies of the Ph chromosome is very rare in CML, even though the appearance of the second Ph is one of the most com- mon changes accompanying blastic phase of the disease. We have recent ly exam- ined a very s imilar pat ient wi th CML who at the onset of blastic phase developed a complex hypo t r ip lo id karyotype with four copies of the Ph chromosome in the s temline cells. The pat ient was a 59-year-old white female whose diagnosis of Ph- posi t ive CML was made in November 1980. She presented with splenomegaly and WBC of 100,000 with 40% mature granulocytes, 22% metamyelocytes , 17% myelo- cytes, 10% promyelocytes , 5% blasts, and 6% lymphocytes . The init ial t reatment with busulfan resul ted in a rap id decrease of the leukocytes and splenomegaly. She remained in the chronic phase of CML over the next 5 years requiring treatment with busulfan on four occasions for fever and splenomegaly. In January 1986 the pat ient deve loped fever and splenomegaly, and the WBC increased to 22,000 with 22% blast cells. The bone marrow showed replacement of normal elements with myeloblasts consis tent wi th CML in accelerated phase.

Cytogenetic analysis of the bone marrow aspirate showed a modal karyotype 59,XX, + 6, + 6, + 8, - 10, + 11, + 12, + 19, + 19, + 20, - 21, - 22, + 2[del(10)(q11.2),2] t(10;21)(q11.2;q22)+4Ph. Forty-one percent of the cells showed four Ph chromosomes with the remaining containing from one to three copies of the Ph.

The pat ient received a course of chemotherapy consist ing of daunomycin , cyto- sine arabinoside, vincris t ine, and prednisone, which resul ted in a part ial cl inical remission after 4 weeks. This correlated with the decl ine in the percentage of cells carrying mul t ip le copies of the Ph chromosome from 87% to 25% on January 30, 1986. Two weeks later, however, the percentage of cells with mul t ip le copies of Ph chromosome increased to 50% and the pat ient re lapsed cl inical ly, short ly thereafter (Table 1). The second course of chemotherapy resulted, again, in part ial remission. The pat ient d ied in June 1986.

The unusual increase in the number of copies of the Ph chromosome in our case is very s imilar to that descr ibed by Kovacs et al. [1]. In addi t ion, we were able to pos i t ive ly correlate the cl inical course of the disease with the propor t ion of cells in the bone marrow carrying mul t ip le copies of the Ph chromosome.

LONGINA GIBAS LAIRD JACKSON

Division of Medical Genetics Thomas Jefferson University

Philadelphia, PA 10107

FREDERICK M. FELLIN Cardeza Foundation for Hematologic Research Thomas Jefferson University

Philadelphia, PA 10107

Received September 29, 1986; accepted October 8, 1986.

179

Page 2: A case of chronic myelogenous leukemia with four Philadelphia chromosomes

180 L. Gibas , L. Jackson , a n d F. M. Fe l l i n

T a b l e 1 N u m b e r of c o p i e s of P h c h r o m o s o m e in b o n e m a r r o w a sp i r a t e

Date of examination 1 × Ph (%) 2-4 × Ph (%) Clinical picture

1/3/86 13 87 Blastic phase 1/30/86 75 25 Partial remission 2/11/86 50 50 Relapse

REFERENCE

1. Kovacs, G, Georgii A, IViainzer K (1986): Three isodicentric Philadelphia chromosomes in acute phase of chronic myeloid leukemia: A case report. Cancer Genet Cytogenet 20:29-33.