Hodgl 's Disease and Secondary Philadelphia Chromosome Positive Chronic Myelogenous Leukemia
We read with great interest the recent paper p u b l i s h e d by Verhoef et al. [1], who described a case of P h i l a d e l p h i a c h r o m o s o m e positive (Ph + ) chronic myelogenous leukemia (CML) occurring 8 years after a diagnosed and cured Hodgkin's disease (HD). We w o u l d like to take this o p p o r t u n i t y to report a similar case that we have observed in our institution. A male patient, born in 1934, presented in 1972 with an isolated mediastinal mass w h i c h was diagnosed as HD. He u n d e r w e n t local radiotherapy (40 gray) and received m o n t h l y c h e m o t h e r a p y for 2 years (Vinblastine: 8 mg intravenous), leading to a complete remission. In May 1988, on a routine blood examination, an increased level of white blood cells (WBC) and platelets (30.5 x 10~/L and 1.458 x 10~/L, respectively) was found. The differential WBC count showed 3% myeloblasts, 5% promyelocytes, 5% myelocytes, 5% metamyelocytes, 50% neutrophils, 6% eosinophils, 2% basophils, 20% lymphocytes, and 4% monocytes. Cytogenetic analysis was performed on a blood sample and s h o w e d in all 30 metaphases analyzed a t(9;22) (q34;q11) [9]. The diagnosis of CML was confirmed by molecular biology carried out on cells collected by cytopheresis. The Southern-blot analysis s h o w e d a bcr rearrangement localized in the F3 segment of the major breakpoint cluster region (MBCR). The patient was treated by alpha-interferon 2-b (IFN), 5 M U/m 2 daily. In May 1989, one year after IFN therapy was started, the patient was still unresponsive to the treatment. A new karyotype carried out at that time showed not only the t(9;22) but new abnormalities w h i c h i n c l u d e d a + 8 and an i(17q) in all the 25 metaphases examined. The patient was t r a n s p l a n t e d (double autologous blood stem-cell transplantation : ABSCT), but died 7 months after the second ABSCT in blast crisis. Secondary CML after HD is infrequent [1, 4] and has been d o c u m e n t e d less often than acute leukemias or solid tumors secondary to HD [3, 4, 5, 8]. These secondary malignancies occur, generally, 3 to 9 years after the initial diagnosis of HD [3] with a peak at 5 years [6, 7] and have been m a i n l y observed after extended-field radiation therapy [9] or r a d i o c h e m o t h e r a p y [3, 6, 9, 10]. There are several points to be considered in this case report: Firstly, the inefficacy of IFN therapy for a standard-risk CML patient with the exception of an increased level of platelets at diagnosis. Secondly, the rapid a p p e a r a n c e of cytogenetic abnormalities, while the patient was undergoing IFN, was an unusual observation in our experience. Thirdly, the delay between the initial diagnosis of HD and the onset of CML was very long (16 years). We must e m p h a s i z e the fact that the patient d i d not receive extended radiation therapy or alkylating agents as treatment for his HD. This observation u n d e r l i n e s the problem of the long-term follow-up required for HD, in particular in young patients. In addition, this case report adds to the literature a new case of CML occurring as a secondary malignancy to cured HD.
277 © 1991 Elsevier Science Publishing Co., Inc. 655 A v e n u e of the Americas, New York, NY 10010
Cancer Genet Cytogenet 55:277 278 (1991) 0165-4608/91/$03.50
278
Letter to the Editor
K. B O U A B D A L L A H G. M A R I T J. REIFFERS A. B R O U S T E T C. B I L H O U - N A B E R A
z. Q. WEN P. BERNARD
S e r v i c e des M a l a d i e s du Sang Centre Frangois M a g e n d i e A v e n u e de M a g e l l a n 33604 Pessac France Laboratoire de G6n6tique des L e u c 6 m i e s U n i v e r s i t 6 de B o r d e a u x II 146 Rue L6o Saignat 33076 B o r d e a u x France
The authors thank Dr. A. Rice for helpful corrections, and Mrs. M. C. Bazile for typing the manuscript.
REFERENCES 1. Verhoef GEG, Demuynek H, Stul MS, Cassiman Jl, Mecucci C, Van Den Berghe H, Boogaerts MA (1990): Philadelphia chromosome-positive chronic myelogenous leukemia in treated Hodgkin's Disease. Cancer Genet Cytogenet 49:171-176. 2. Rowley JD (1973): A new consistent chromosome abnormality in chronic myelogenous leukemia identified by quinacrine fluorescense and giemsa staining. Nature 243:290-293. 3. Blayney DW, Longo DL, Young RC, Greene MH, Hubbard SM, Postal MG, De Vita V (1987): Decreasing risk of leukemia with prolonged follow-up after chemotherapy and radiotherapy for Hodgkin's disease. N Engl J Med 316:710-714. 4. Tucker MA, Coleman CN, Cox RS, Varghese A, Rosenberg SA (1988): Risk of second cancers after treatment for Hodgkin's disease. N Engl J Med 318:76-81. 5. Valagussa P, Santoro A, Fossati-Bellani F, Banff A, Bonadonna G (1986): Second acute leukemia and other malignancies following treatment for Hodgkin's disease. J Clin Oncol 4:830-837. 6. Kaldor JM, Day NE, Clarke EA, Van Lecuwen FE, Henry-Amer M, Fiorentino MV, Bell J, Pedersen D, Band P, Assouline D, Koch M, Choi W, Prior P, Blair V, Langmark F, Pompe Kirn V, Neal F, Peters D, Pfeiffer R, Karjatainen S, Cuzick J, Sutcliffe SB, Somers P, PellacCosset B: Leukemia following Hodgkin's disease. N Engl J Med 322:7-13. 7. Vanlecuwen FE, Somers R, Taal BG, Van Heerde P, Coster B, Dozeman T, Huisman SJ, Hart AAM (1989): Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease. J Clin Oncol 7:1046-1058. 8. Kalestky AJ, Bertino JR, Farber LR, Prosnitz LR, Kapp DS, Fisher D, Portlock CS (1986): Second neoplasms in patients with Hodgkin's disease following combined modality therapy. The Yale experience. I Clin Oncol 4:311-317. 9. Andrieu IM, Ifrah N, Zayen C, Fermanian J, Coscas Y, Flandrin G (1990): Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease. J Clin Oncol 8:1148-1154. 10. Papa G, Mauro FR, Cimino G, Pisani F, Tabilio A, Dilonardo A (1989): Secondary myelodysplasia/leukemia complex. Bone Marrow Transplant 4:141-142.
We read with great interest the recent paper p u b l i s h e d by Verhoef et al. [1], who described a case of P h i l a d e l p h i a c h r o m o s o m e positive (Ph + ) chronic myelogenous leukemia (CML) occurring 8 years after a diagnosed and cured Hodgkin's disease (HD). We w o u l d like to take this o p p o r t u n i t y to report a similar case that we have observed in our institution. A male patient, born in 1934, presented in 1972 with an isolated mediastinal mass w h i c h was diagnosed as HD. He u n d e r w e n t local radiotherapy (40 gray) and received m o n t h l y c h e m o t h e r a p y for 2 years (Vinblastine: 8 mg intravenous), leading to a complete remission. In May 1988, on a routine blood examination, an increased level of white blood cells (WBC) and platelets (30.5 x 10~/L and 1.458 x 10~/L, respectively) was found. The differential WBC count showed 3% myeloblasts, 5% promyelocytes, 5% myelocytes, 5% metamyelocytes, 50% neutrophils, 6% eosinophils, 2% basophils, 20% lymphocytes, and 4% monocytes. Cytogenetic analysis was performed on a blood sample and s h o w e d in all 30 metaphases analyzed a t(9;22) (q34;q11) [9]. The diagnosis of CML was confirmed by molecular biology carried out on cells collected by cytopheresis. The Southern-blot analysis s h o w e d a bcr rearrangement localized in the F3 segment of the major breakpoint cluster region (MBCR). The patient was treated by alpha-interferon 2-b (IFN), 5 M U/m 2 daily. In May 1989, one year after IFN therapy was started, the patient was still unresponsive to the treatment. A new karyotype carried out at that time showed not only the t(9;22) but new abnormalities w h i c h i n c l u d e d a + 8 and an i(17q) in all the 25 metaphases examined. The patient was t r a n s p l a n t e d (double autologous blood stem-cell transplantation : ABSCT), but died 7 months after the second ABSCT in blast crisis. Secondary CML after HD is infrequent [1, 4] and has been d o c u m e n t e d less often than acute leukemias or solid tumors secondary to HD [3, 4, 5, 8]. These secondary malignancies occur, generally, 3 to 9 years after the initial diagnosis of HD [3] with a peak at 5 years [6, 7] and have been m a i n l y observed after extended-field radiation therapy [9] or r a d i o c h e m o t h e r a p y [3, 6, 9, 10]. There are several points to be considered in this case report: Firstly, the inefficacy of IFN therapy for a standard-risk CML patient with the exception of an increased level of platelets at diagnosis. Secondly, the rapid a p p e a r a n c e of cytogenetic abnormalities, while the patient was undergoing IFN, was an unusual observation in our experience. Thirdly, the delay between the initial diagnosis of HD and the onset of CML was very long (16 years). We must e m p h a s i z e the fact that the patient d i d not receive extended radiation therapy or alkylating agents as treatment for his HD. This observation u n d e r l i n e s the problem of the long-term follow-up required for HD, in particular in young patients. In addition, this case report adds to the literature a new case of CML occurring as a secondary malignancy to cured HD.
277 © 1991 Elsevier Science Publishing Co., Inc. 655 A v e n u e of the Americas, New York, NY 10010
Cancer Genet Cytogenet 55:277 278 (1991) 0165-4608/91/$03.50
278
Letter to the Editor
K. B O U A B D A L L A H G. M A R I T J. REIFFERS A. B R O U S T E T C. B I L H O U - N A B E R A
z. Q. WEN P. BERNARD
S e r v i c e des M a l a d i e s du Sang Centre Frangois M a g e n d i e A v e n u e de M a g e l l a n 33604 Pessac France Laboratoire de G6n6tique des L e u c 6 m i e s U n i v e r s i t 6 de B o r d e a u x II 146 Rue L6o Saignat 33076 B o r d e a u x France
The authors thank Dr. A. Rice for helpful corrections, and Mrs. M. C. Bazile for typing the manuscript.
REFERENCES 1. Verhoef GEG, Demuynek H, Stul MS, Cassiman Jl, Mecucci C, Van Den Berghe H, Boogaerts MA (1990): Philadelphia chromosome-positive chronic myelogenous leukemia in treated Hodgkin's Disease. Cancer Genet Cytogenet 49:171-176. 2. Rowley JD (1973): A new consistent chromosome abnormality in chronic myelogenous leukemia identified by quinacrine fluorescense and giemsa staining. Nature 243:290-293. 3. Blayney DW, Longo DL, Young RC, Greene MH, Hubbard SM, Postal MG, De Vita V (1987): Decreasing risk of leukemia with prolonged follow-up after chemotherapy and radiotherapy for Hodgkin's disease. N Engl J Med 316:710-714. 4. Tucker MA, Coleman CN, Cox RS, Varghese A, Rosenberg SA (1988): Risk of second cancers after treatment for Hodgkin's disease. N Engl J Med 318:76-81. 5. Valagussa P, Santoro A, Fossati-Bellani F, Banff A, Bonadonna G (1986): Second acute leukemia and other malignancies following treatment for Hodgkin's disease. J Clin Oncol 4:830-837. 6. Kaldor JM, Day NE, Clarke EA, Van Lecuwen FE, Henry-Amer M, Fiorentino MV, Bell J, Pedersen D, Band P, Assouline D, Koch M, Choi W, Prior P, Blair V, Langmark F, Pompe Kirn V, Neal F, Peters D, Pfeiffer R, Karjatainen S, Cuzick J, Sutcliffe SB, Somers P, PellacCosset B: Leukemia following Hodgkin's disease. N Engl J Med 322:7-13. 7. Vanlecuwen FE, Somers R, Taal BG, Van Heerde P, Coster B, Dozeman T, Huisman SJ, Hart AAM (1989): Increased risk of lung cancer, non-Hodgkin's lymphoma, and leukemia following Hodgkin's disease. J Clin Oncol 7:1046-1058. 8. Kalestky AJ, Bertino JR, Farber LR, Prosnitz LR, Kapp DS, Fisher D, Portlock CS (1986): Second neoplasms in patients with Hodgkin's disease following combined modality therapy. The Yale experience. I Clin Oncol 4:311-317. 9. Andrieu IM, Ifrah N, Zayen C, Fermanian J, Coscas Y, Flandrin G (1990): Increased risk of secondary acute nonlymphocytic leukemia after extended-field radiation therapy combined with MOPP chemotherapy for Hodgkin's disease. J Clin Oncol 8:1148-1154. 10. Papa G, Mauro FR, Cimino G, Pisani F, Tabilio A, Dilonardo A (1989): Secondary myelodysplasia/leukemia complex. Bone Marrow Transplant 4:141-142.
