lnt J Clin Lab Res 22: 122-123, 1992
9 Springer-Verlag1992
Letter to the editor
Is therapy with cytostatics obsolete in hairy-cell leukemia? E Franchi 1, p. Seminara 1, G. Codacci-Pisanelli 1, and P. Bianco 2 i Department of III Clinical Medicine, University "La Sapienza", Rome, Italy 2 Department of Biopathology, University "La Sapienza", Rome, Italy Sir, The medical treatment of hairy-cell leukemia (HCL) is basically represented by a-interferon (IFN). However, after controversial studies on pentostatin, the impressive preliminary report of Piro et al. [4] seems to advocate the use of chemotherapeutic agents again. We report a HCL patient who responded much more strikingly to available anticancer agents than to IFN. A 46-year-old Caucasian male first presented in 1979 with a H C L leukopenic variant. He received four courses of PROVECIP regimen, a C/MOPP-like protocol of Italian design [3], followed by a 1-year treatment with monthly cycles of chlorambucil. Complete remission (CR) was achieved and unexpectedly lasted for 10 years, documented by repeated marrow biopsies, computed tomography and spleen echography. Correspondence to: F. Franchi, Via di S. Agnese 12, 1-00198, Rome,
Italy
Fig. 1 a, b. Bone marrow biopsy following: a 6 months of single interferon treatment and b after three courses of chemotherapy. In a the marrow is extensively occupied by hairy cells, arranged in the
The patient relapsed at the end of 1989; 3 x l 0 6 IU I F N were then administered every other day for 5 months. In June 1990 he was still febrile and anemic, a bone marrow biopsy showed only slight improvement (Fig. 1 a), and spleen and lymph node enlargement remained unchanged. At that time, I F N had to be withdrawn due to intervening vasculitis, increase of blood pressure, hypertensive encephalopathy and very severe psychic depression. Chemotherapy was then re-estabilished with three monthly courses of vinblastine (0.15mg/kg) in an 8-h slow infusion and idarubicin (5 mg/m 2 push) on days 1, 2 and 3. Maximum leukocyte nadir was observed after the first course (0.8 x 1 0 9 white blood cells/l). Following chemotherapy, his clinical condition improved dramatically and hematological parameters rapidly normalized. Cutaneous reactions and T cell subsets, which remained impaired after I F N treatment, improved after chemotherapy. A further biopsy 1 month later showed a virtually complete restoration of
characteristic "loose" pattern; after chemotherapy b normal hemopoiesis is restored
E Franchi et al.: Is therapy with cytostatics obsolete in hairy-cell leukemia'? hemopoietic m a r r o w (Fig. 1 b). Seventeen months later the patient still r e m a i n s in C R off therapy. Some long-surviving cases o f H C L have been reported in the absence o f medical t h e r a p y [5] or after treatment with alkylating agents [1]. It is thus possible that o u r patient belongs to a subset o f H C L subjects with a spontaneous g o o d prognosis. Even if this is the case, it is noteworthy that, in o u r patient, traditional chemotherapy p r o d u c e d excellent results on two occasions. The activity o f the a n t h r a c y c l i n e - c o n t a i n i n g schedule was surprisingly superior to I F N . R e s p o n s e to c h e m o t h e r a p y following I F N failure is a clinical event that has already been reported [6]. Several complications o f I F N treatment, including those described in our patient, are a l r e a d y known. It is certainly difficult to object against a t r e a t m e n t that yields m o r e than 80% RR; nevertheless, we should not underestimate the adverse effects o f I F N a n d should bear in mind the rarity o f complete remissions o b t a i n e d with this therapy. We think that the best role o f I F N s in oncology is yet to be defined. C o m b i n a t i o n o f I F N with c h e m o t h e r a p y m a y be optimal as I F N can act as a chemosensitizer [2]. In our patient, this effect o f I F N c a n n o t be excluded. Classical anticancer agents m a y still have a role in H C L therapy.
123
Acknowledgements. Supported by grants from the Italian National Research Council, Special Project "Oncology", contract 88.00672.44 and "National Committee for Technological Research and Innovation", contract 90.02030.CT11.
References 1. Davis TE, Waterbury L, Abeloff M, et al., Leukemic reticuloendotheliosis. Report of a case with prolonged remission following chemotherapy. Arch Intern Med 136:620, 1976 2. Iaffaioli RS, Palmieri G, Contegiacomo A, et al., Restoration of drug susceptibility by interferons in patients with drug-resistant tumors. In: Castagnetta L, Nenci I (eds) Biology and biochemistry of normal and cancer cell growth. Harwood, Chur, pp 141-148, 1987 3. Mandelli F, Bianchi C, Baroni CD, et al., Treatment of non Hodgkin's lymphoma with PROVECIP (procarbazine, vinblastine, cyclophosphamide and prednisone). Haematotogica (Pavia) 61:108. 1980 4. Piro LD, Carrera CL Carson DA, et al., Lasting remission in hairy-cell leukemia induced by a single infusion of 2chlorodeoxyadenosine. N Engl J Med 322: 1117, 1990 5. Temple JD, Harrington WJ, McCoy CB, The relapse of hairy cell leukemia after a 32-year remission. Cancer 67: 1945, 1991 6. Zinzani PL, Lauria F, Buzzi M, et al., Hairy cell leukemia variant: a morphologic, immunologic and clinical study of 7 cases. Haematologica (Pavia) 75: 54, 1990
9 Springer-Verlag1992
Letter to the editor
Is therapy with cytostatics obsolete in hairy-cell leukemia? E Franchi 1, p. Seminara 1, G. Codacci-Pisanelli 1, and P. Bianco 2 i Department of III Clinical Medicine, University "La Sapienza", Rome, Italy 2 Department of Biopathology, University "La Sapienza", Rome, Italy Sir, The medical treatment of hairy-cell leukemia (HCL) is basically represented by a-interferon (IFN). However, after controversial studies on pentostatin, the impressive preliminary report of Piro et al. [4] seems to advocate the use of chemotherapeutic agents again. We report a HCL patient who responded much more strikingly to available anticancer agents than to IFN. A 46-year-old Caucasian male first presented in 1979 with a H C L leukopenic variant. He received four courses of PROVECIP regimen, a C/MOPP-like protocol of Italian design [3], followed by a 1-year treatment with monthly cycles of chlorambucil. Complete remission (CR) was achieved and unexpectedly lasted for 10 years, documented by repeated marrow biopsies, computed tomography and spleen echography. Correspondence to: F. Franchi, Via di S. Agnese 12, 1-00198, Rome,
Italy
Fig. 1 a, b. Bone marrow biopsy following: a 6 months of single interferon treatment and b after three courses of chemotherapy. In a the marrow is extensively occupied by hairy cells, arranged in the
The patient relapsed at the end of 1989; 3 x l 0 6 IU I F N were then administered every other day for 5 months. In June 1990 he was still febrile and anemic, a bone marrow biopsy showed only slight improvement (Fig. 1 a), and spleen and lymph node enlargement remained unchanged. At that time, I F N had to be withdrawn due to intervening vasculitis, increase of blood pressure, hypertensive encephalopathy and very severe psychic depression. Chemotherapy was then re-estabilished with three monthly courses of vinblastine (0.15mg/kg) in an 8-h slow infusion and idarubicin (5 mg/m 2 push) on days 1, 2 and 3. Maximum leukocyte nadir was observed after the first course (0.8 x 1 0 9 white blood cells/l). Following chemotherapy, his clinical condition improved dramatically and hematological parameters rapidly normalized. Cutaneous reactions and T cell subsets, which remained impaired after I F N treatment, improved after chemotherapy. A further biopsy 1 month later showed a virtually complete restoration of
characteristic "loose" pattern; after chemotherapy b normal hemopoiesis is restored
E Franchi et al.: Is therapy with cytostatics obsolete in hairy-cell leukemia'? hemopoietic m a r r o w (Fig. 1 b). Seventeen months later the patient still r e m a i n s in C R off therapy. Some long-surviving cases o f H C L have been reported in the absence o f medical t h e r a p y [5] or after treatment with alkylating agents [1]. It is thus possible that o u r patient belongs to a subset o f H C L subjects with a spontaneous g o o d prognosis. Even if this is the case, it is noteworthy that, in o u r patient, traditional chemotherapy p r o d u c e d excellent results on two occasions. The activity o f the a n t h r a c y c l i n e - c o n t a i n i n g schedule was surprisingly superior to I F N . R e s p o n s e to c h e m o t h e r a p y following I F N failure is a clinical event that has already been reported [6]. Several complications o f I F N treatment, including those described in our patient, are a l r e a d y known. It is certainly difficult to object against a t r e a t m e n t that yields m o r e than 80% RR; nevertheless, we should not underestimate the adverse effects o f I F N a n d should bear in mind the rarity o f complete remissions o b t a i n e d with this therapy. We think that the best role o f I F N s in oncology is yet to be defined. C o m b i n a t i o n o f I F N with c h e m o t h e r a p y m a y be optimal as I F N can act as a chemosensitizer [2]. In our patient, this effect o f I F N c a n n o t be excluded. Classical anticancer agents m a y still have a role in H C L therapy.
123
Acknowledgements. Supported by grants from the Italian National Research Council, Special Project "Oncology", contract 88.00672.44 and "National Committee for Technological Research and Innovation", contract 90.02030.CT11.
References 1. Davis TE, Waterbury L, Abeloff M, et al., Leukemic reticuloendotheliosis. Report of a case with prolonged remission following chemotherapy. Arch Intern Med 136:620, 1976 2. Iaffaioli RS, Palmieri G, Contegiacomo A, et al., Restoration of drug susceptibility by interferons in patients with drug-resistant tumors. In: Castagnetta L, Nenci I (eds) Biology and biochemistry of normal and cancer cell growth. Harwood, Chur, pp 141-148, 1987 3. Mandelli F, Bianchi C, Baroni CD, et al., Treatment of non Hodgkin's lymphoma with PROVECIP (procarbazine, vinblastine, cyclophosphamide and prednisone). Haematotogica (Pavia) 61:108. 1980 4. Piro LD, Carrera CL Carson DA, et al., Lasting remission in hairy-cell leukemia induced by a single infusion of 2chlorodeoxyadenosine. N Engl J Med 322: 1117, 1990 5. Temple JD, Harrington WJ, McCoy CB, The relapse of hairy cell leukemia after a 32-year remission. Cancer 67: 1945, 1991 6. Zinzani PL, Lauria F, Buzzi M, et al., Hairy cell leukemia variant: a morphologic, immunologic and clinical study of 7 cases. Haematologica (Pavia) 75: 54, 1990
