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Infectious mononucleosis ina child with acute lymphoblastic leukemia
8 7 6 Brief clinical and laboratory observations
REFERENCES 1. Waardenburg, P. J.: A new syndrome combining developmental a.nomalies of the eyelids, eyebrows, and nose root, with pigmentary defects of the iris and head hair and with congenital deafness, Am. J. Human Genet. 3: 195, 1951. 2. DiGeorge, A. M., Olmsted, R. W., and Harley, R. D.: Waardenburg's syndrome, J. PEDIAT. 57: 649, 1960. 3. DiGeorge, A. M., Olmsted, R. W., and Harley,
Infectious mononucleosis in a child with acute lymphoblastic leukemia Beatrice C. Lampkin, M.D.,* Luis Canales, Major, MC, USA, and Alvin M. Mauer, M.D. C [ N G I N NAT]~ O H I O
T~E S U G O 1 ~ S T I O N has been m a d e t h a t acute leukemia a n d infectious mononucleosis in children m a y be caused by the same agent or by closely related agents? If this hypothesis were true, it w o u l d be unlikely thag a p a t i e n t with acute l e u k e m i a would also have coexisting infectious mononucleosis. I t is the p u r p o s e of this p a p e r to r e p o r t the findings of a child w i t h acute lymphoblastic l e u k e m i a who deveioped infectious mononucIeosis durFrom the Department o[ Pediatrics, University of Cincinnati College of Medicine, The Children's Hospital, and The Children's Hospital Research Foundation. Supported by Public Health Service Research Grant CA-04826 from the National Cancer Institute Dr. Lampkin is an Advanced Clinical Fellow of the American Cancer Society, Inc.; Dr. Mauer was a recipient of a Research Career Development Award, and Dr. Canales was on special assignment 'from the OoSce of the Surgeon General, Unite,d States Army, at the time this work was performed. *Address. The Children's Hospital, Cincinnati, Ohio 45229.
The Journal of Pediatrics December 1967
R. D.: Waardenburg's syndrorue, Tr. Am. Acad. Ophth. 64: 816, 1960. 4. Partington, M. W.: Waardenburg's syndrome and heterochromia iridum in a deaf-school population, Canad. M. A. J. 90: 1008, 1964. 5. Hansen, A. C., Ackaouy, G., and Crump, E. P.: Waardenburg's syndrome: Report of a pedigree, J. Nat. M. A. 57: 8, 1965. 6. Rugel, S. J., and Keats, E. U,: Waardenburg's syndrome in six generations of one family, Am. J. Dis. Child. 109: 579, 1965.
ing a d r u g - i n d u c e d remission of the leukemic process.
CASE REPORT This 6-year-old Caucasian boy was found to have acute lymphoblastic leukemia on July 28, I964. A complete remission was induced with prednisone and 6-mercaptopurine and maintained with 6-mercaptopurine. No blood or blood products were administered except during the initial induction period. He was asymptomatic until Nov. 3, 1965, when on a routine clinic visit he complained of having a sore throat and his temperature was found to be 99.2 ~ F. His spleen tip was palpable for the first time since induction of remission. One week later he was tired and anorexic. His spleen was then felt 2 cm. below the left costal margin and remained palpable until Dec. 22, i965, 6 weeks after onset of this illness. The blood findings are shown in Table I. Atypical lymphocytes were present on blood smears for at least 2 weeks. In Table II are shown serological values obtained at time of diagnosis of the leukemia, during the time when atypical lymphocytes were found in his blood and 19 months after this illness. Two weeks after onset of symptoms the heterophil titer was abnormally increased. The titer was still significantly increased after guinea pig kidney absorption but absent after absorption with beef red blood cells. The initial remission of the patient's leukemia lasted until March, 1967. DISCUSSION I n the t y p i c a l p a t i e n t w i t h infectious mononucleosis, tymphocytes constitute m o r e t h a n one half of the white blood cells at some stage of the illness. 2 A l t h o u g h m a n y
Volume 71 Number 6
Brie[ clinical and laboratory observations
Table I. Hematologic data HeIno-
Dates 11/ 3/65 11/10/65
11/17/65 11/24/65
12./22/65
globin WBC Neutro(Gin. per phils cent) (per mm.Q (per cent) 12.4 12.2 12.7 12.4 13.2
4,000 5,000 5,600 8,650 7,000
69 62 54 59 67
Eosinophits (per cent) 3
1
BaSO-phils Lympho(per cytes cent) (per cent) 16 32 37 30 28
1
2
1
877
I
Monocytes (per cent)
Platelets
No. atypical lymphocytes
12 5 7 9 5
Surf. Surf. Surf, Surf. Surf.
None Occ. About 89 About~2 None
Table II. Serological d a t a
I July 28, 1964 ] Nov. 10, 1965 I Nov. 17, 1965 I June 7, 1967 Heterophil Guinea pig kidney absorption Beef red-blood-cell absorption
1: 7
atypical lymphocytes were present in the blood of the patient, the lymphocytes were never found to be the predominant cells. T h e relatively low percentage of lymphocytes present in the blood during the illness might have been due to the immunosuppressive effect of 6-mercaptopurine which was given throughout the course of the disease. Atypical lymphocytes were found in the blood for at least 2 weeks after the heterophils and differential absorption tests were characteristic for infectious mononucleosis. ~ Feldman 4 reported in 1944 an 18-year-old Caucasian male with coexisting lymphatic leukemia and infectious mononucleosis. T h e diagnosis of infectious mononucleosis was confirmed by heterophils and the differential absorption tests. T h e disease had occurred 3 ~ months before the diagnosis of lymphatic leukemia was established. T h e heterophiI titers were negative 6 months after the diagnosis of infectious mononucleosis during a period of severe clinical symptoms from leukemia. Patients with acute leukemia have been reported to have positive heterophil tests, but the results of differential absorption tests are not characteristic of those seen in infectious mononucleosis? I t is possible that the clinical manifestations of infectious mononucleosis as seen in the patient reported by Feldman 4 and in
1 : 56
1 : 448 1 : 112 0
1: 7 0
0
our patient m a y have been different aspects of a disease caused by the same or similar agents. However, it is more likely that the two diseases are unrelated as to etiological agents, particularly since our patient was in remission when the infectious mononucleosis occurred and he had a relapse of leukemia 16 months later. SUMMARY
A child is described with acute lymphoblastic leukemia who developed infectious mononucleosis during a remission maintained by 6-mercaptopurine. REFERENCES
1. Benyesh-Melnick, M.: Electron microscopic and tissue culture studies of acute leukemia and infectious mononucleosis in children, in Wingvist, G., editor: Comparative leukaemia research; Wenner-Gren Center International Symposium Series, London, 1966, Pergamon Press, vol. 6, pp. 23-26. 2. Hoagland, R. J.: Infections mononucleosis, Am. J. Med. 13: 158, 1952. 3. Bender, C. E.: Interpretation of hematologic and serologic findings in the diagnosis o~ infectious mononucleosis, Ann. Int. Med. 49: 852, 1958. 4. Feldman, F., and Yarvis, J. J.: Manifestations of hemolytic phenomenon and infectious mononucleosis in a case of lymphatic leukemia, New York State J. Med. 44: 1693, 1944. 5. Southam, C. M., Goldsmith, Y., and Burchenal, J. H.: Heterophile antibodies and antigens in neoplastic diseases, Cancer 4: 1036, 195i.
REFERENCES 1. Waardenburg, P. J.: A new syndrome combining developmental a.nomalies of the eyelids, eyebrows, and nose root, with pigmentary defects of the iris and head hair and with congenital deafness, Am. J. Human Genet. 3: 195, 1951. 2. DiGeorge, A. M., Olmsted, R. W., and Harley, R. D.: Waardenburg's syndrome, J. PEDIAT. 57: 649, 1960. 3. DiGeorge, A. M., Olmsted, R. W., and Harley,
Infectious mononucleosis in a child with acute lymphoblastic leukemia Beatrice C. Lampkin, M.D.,* Luis Canales, Major, MC, USA, and Alvin M. Mauer, M.D. C [ N G I N NAT]~ O H I O
T~E S U G O 1 ~ S T I O N has been m a d e t h a t acute leukemia a n d infectious mononucleosis in children m a y be caused by the same agent or by closely related agents? If this hypothesis were true, it w o u l d be unlikely thag a p a t i e n t with acute l e u k e m i a would also have coexisting infectious mononucleosis. I t is the p u r p o s e of this p a p e r to r e p o r t the findings of a child w i t h acute lymphoblastic l e u k e m i a who deveioped infectious mononucIeosis durFrom the Department o[ Pediatrics, University of Cincinnati College of Medicine, The Children's Hospital, and The Children's Hospital Research Foundation. Supported by Public Health Service Research Grant CA-04826 from the National Cancer Institute Dr. Lampkin is an Advanced Clinical Fellow of the American Cancer Society, Inc.; Dr. Mauer was a recipient of a Research Career Development Award, and Dr. Canales was on special assignment 'from the OoSce of the Surgeon General, Unite,d States Army, at the time this work was performed. *Address. The Children's Hospital, Cincinnati, Ohio 45229.
The Journal of Pediatrics December 1967
R. D.: Waardenburg's syndrorue, Tr. Am. Acad. Ophth. 64: 816, 1960. 4. Partington, M. W.: Waardenburg's syndrome and heterochromia iridum in a deaf-school population, Canad. M. A. J. 90: 1008, 1964. 5. Hansen, A. C., Ackaouy, G., and Crump, E. P.: Waardenburg's syndrome: Report of a pedigree, J. Nat. M. A. 57: 8, 1965. 6. Rugel, S. J., and Keats, E. U,: Waardenburg's syndrome in six generations of one family, Am. J. Dis. Child. 109: 579, 1965.
ing a d r u g - i n d u c e d remission of the leukemic process.
CASE REPORT This 6-year-old Caucasian boy was found to have acute lymphoblastic leukemia on July 28, I964. A complete remission was induced with prednisone and 6-mercaptopurine and maintained with 6-mercaptopurine. No blood or blood products were administered except during the initial induction period. He was asymptomatic until Nov. 3, 1965, when on a routine clinic visit he complained of having a sore throat and his temperature was found to be 99.2 ~ F. His spleen tip was palpable for the first time since induction of remission. One week later he was tired and anorexic. His spleen was then felt 2 cm. below the left costal margin and remained palpable until Dec. 22, i965, 6 weeks after onset of this illness. The blood findings are shown in Table I. Atypical lymphocytes were present on blood smears for at least 2 weeks. In Table II are shown serological values obtained at time of diagnosis of the leukemia, during the time when atypical lymphocytes were found in his blood and 19 months after this illness. Two weeks after onset of symptoms the heterophil titer was abnormally increased. The titer was still significantly increased after guinea pig kidney absorption but absent after absorption with beef red blood cells. The initial remission of the patient's leukemia lasted until March, 1967. DISCUSSION I n the t y p i c a l p a t i e n t w i t h infectious mononucleosis, tymphocytes constitute m o r e t h a n one half of the white blood cells at some stage of the illness. 2 A l t h o u g h m a n y
Volume 71 Number 6
Brie[ clinical and laboratory observations
Table I. Hematologic data HeIno-
Dates 11/ 3/65 11/10/65
11/17/65 11/24/65
12./22/65
globin WBC Neutro(Gin. per phils cent) (per mm.Q (per cent) 12.4 12.2 12.7 12.4 13.2
4,000 5,000 5,600 8,650 7,000
69 62 54 59 67
Eosinophits (per cent) 3
1
BaSO-phils Lympho(per cytes cent) (per cent) 16 32 37 30 28
1
2
1
877
I
Monocytes (per cent)
Platelets
No. atypical lymphocytes
12 5 7 9 5
Surf. Surf. Surf, Surf. Surf.
None Occ. About 89 About~2 None
Table II. Serological d a t a
I July 28, 1964 ] Nov. 10, 1965 I Nov. 17, 1965 I June 7, 1967 Heterophil Guinea pig kidney absorption Beef red-blood-cell absorption
1: 7
atypical lymphocytes were present in the blood of the patient, the lymphocytes were never found to be the predominant cells. T h e relatively low percentage of lymphocytes present in the blood during the illness might have been due to the immunosuppressive effect of 6-mercaptopurine which was given throughout the course of the disease. Atypical lymphocytes were found in the blood for at least 2 weeks after the heterophils and differential absorption tests were characteristic for infectious mononucleosis. ~ Feldman 4 reported in 1944 an 18-year-old Caucasian male with coexisting lymphatic leukemia and infectious mononucleosis. T h e diagnosis of infectious mononucleosis was confirmed by heterophils and the differential absorption tests. T h e disease had occurred 3 ~ months before the diagnosis of lymphatic leukemia was established. T h e heterophiI titers were negative 6 months after the diagnosis of infectious mononucleosis during a period of severe clinical symptoms from leukemia. Patients with acute leukemia have been reported to have positive heterophil tests, but the results of differential absorption tests are not characteristic of those seen in infectious mononucleosis? I t is possible that the clinical manifestations of infectious mononucleosis as seen in the patient reported by Feldman 4 and in
1 : 56
1 : 448 1 : 112 0
1: 7 0
0
our patient m a y have been different aspects of a disease caused by the same or similar agents. However, it is more likely that the two diseases are unrelated as to etiological agents, particularly since our patient was in remission when the infectious mononucleosis occurred and he had a relapse of leukemia 16 months later. SUMMARY
A child is described with acute lymphoblastic leukemia who developed infectious mononucleosis during a remission maintained by 6-mercaptopurine. REFERENCES
1. Benyesh-Melnick, M.: Electron microscopic and tissue culture studies of acute leukemia and infectious mononucleosis in children, in Wingvist, G., editor: Comparative leukaemia research; Wenner-Gren Center International Symposium Series, London, 1966, Pergamon Press, vol. 6, pp. 23-26. 2. Hoagland, R. J.: Infections mononucleosis, Am. J. Med. 13: 158, 1952. 3. Bender, C. E.: Interpretation of hematologic and serologic findings in the diagnosis o~ infectious mononucleosis, Ann. Int. Med. 49: 852, 1958. 4. Feldman, F., and Yarvis, J. J.: Manifestations of hemolytic phenomenon and infectious mononucleosis in a case of lymphatic leukemia, New York State J. Med. 44: 1693, 1944. 5. Southam, C. M., Goldsmith, Y., and Burchenal, J. H.: Heterophile antibodies and antigens in neoplastic diseases, Cancer 4: 1036, 195i.