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Cranial irradiation and lymphocyte subpopulations in acute lymphocytic leukemia
Volume 92 Number 5 and subsequently meningitis occurred despite the fact that the mechanisms which usually protect the eye were intact. The progression of the infection in this patient may have been related to the fact that the conjunctivitis was treated locally only; no systemic antibiotics were administered until clinical evidence of meningitis was present. There are some reports of good results in the treatment of meningococcal conjunctivitis with topical therapy alone? but at least one previously reported patient developed meningococcemia following the exclusive use of local therapy with sulfacetamide? Parenteral penicillin is therefore recommended in addition to local therapy because of the risk of meningococcemia or meningitis.~ As a result of this experience it is prudent, in addition to culturing, to examine gram-stained smears of exudate from all cases of conjunctivitis in children. Examination of the smears will not give a definitive diagnosis but gramnegative diplococci resembling Neisseria can be differen-
Cranial irradiation and lymphocyte subpopulations in acute lymphocytic leukemia Kunio Kishida, M.D.,* Sumio Miyazaki, M.D., Hiromiehi Take, M.D., Takeo Fujimoto, M.D., Hiroyuki Shin, M.D., Kuniakl Sasaki, M.D., and Nagahide Goya, M.D., Fukuoka, Japan
CRANIAL IRRADIATION was administered to prevent central nervous system involvement in patients with acute lymphocytic leukemia. The numbers of T and B lymphocytes in patients were studied to determine the relative changes. Both T and B lymphocytes were affected by irradiation; B lymphocytes were markedly depleted, but the recovery was more rapid than that of T lymphocytes. From the Department of Pediatrics, Faculty of Medicine, Kyushu University. Supported by grants from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare of Japan. *Reprint address: Departmentof Pediatrics, Facultyof Medicine, Kyushu University,Maidashi, Highashi-ku, Fukuoka 812, Japan.
0022-3476/78/0592-0785500.20/0 9 1978 The C. V. Mosby Co.
Brief clinical and laboratory observations
785
tiated from the usual gram-positive cocci. When gramnegative diplococci are identified, systemic therapy should be instituted in addition to local therapy while awaiting a bacteriologic diagnosis.
REFERENCES 1. Stuart RD, and McWalter D: Primary meningococcal conjunctivitis in children, Lancet 1:246, 1948. 2. Little JM, Centifanto YM, and Kaufman HE: Studies of immunoglobins in human tears, Am J Ophthal 68:898, 1969. 3. Hobart C: Lysozyme in ophthalmic conditions, Am J Ophthal 33:1409, 1950. 4. Gray JDA, and Lambert RA: Meningococcal conjunctivitis, Br Med J 1:17, 1949. 5. Dillman CE: Meningococcemia following meningococcal conjunctivitis, South Med J 60:456, 1967. 6. Newton DA, and Wilson WG: Primary meningococcal conjunctivitis, Pediatrics 60:104, 1977.
MATERIAL AND M E T H O D S Thirty-two children with ALL one to 14 years of age were studied. Both T and B lymphocytes were counted in 14 normal children two and 13 years of age. Initial therapy, for ALL consisted of four to six weeks of vincristine and prednisolone administration. After complete remission was obtained, each child was given cranial irradiation (2,400 rads) during a four- to five-week span in an effort to prevent CNS involvement. Abbreviations used CNS: central nervous system ALL: acute lymphocytic leukemia Lymphocytes were obtained from heparinized venous blood. Leukocyte-rich plasma was incubated with ironcontaining lymphocyte-separating reagent (Technicon Instruments Corporation) for 30 minutes at 37~ 1 The mixture was placed on a Ficoll-Hypaque gradient and centrifuged at 400 g for 45 minutes. The cells at the interface were collected and washed three times with phosphate-buffered saline. The T lymphocytes were identified by the spontaneous sheep red blood cell rosette (E rosette technique); and B lymphocytes by receptors for activated complement (EAC rosette [echnique)? '-' RESULTS The absolute numbers of T and B lymphocytes are shown in the Fig. 1. B lymphocytes fell after cranial irradiation and virtually returned to normal 12 months
786
Brief clinical and laboratory observations
The Journal of Pediatrics May 1978
/mr4 400(
300( O
.
200C
lOOC
,
Complete Remission
,
.
.
.
Radiation
.
3 Mo After Radiation
6 - ~ - ~ 2 Radiation
Mo-'~Tte?" Radiation
Fig. 1. The absolute number ofT and B lymphocytes solid dots; B lymphocytes, open circles; T lymphocytes, dashed fine; normal range derived from controls.
after irradiation. The absolute number of T lymphocytes also fell after radiotherapy, but the decline was proportionately less than that of the B lymphocytes. DISCUSSION These data indicate that both T and B lympbocytes are affected by cranial irradiation. Although B lymphocytes showed greater depression, the recovery was more rapid than that of T lymphocytes. Kataoka et al 3observed that T lymphocytes consisted of two distinct subpopulations with respect to radiosensitivity, and B lymphocytes were extremely sensitive to radiation. Serial studies of numbers of circulating T and B lymphocytes in children with ALL by Reid et aP showed a marked fall in the number of B cells, relatively greater than that of T cells. In other types of malignancy, Stjernsward et al ~ noted a decrease in T lymphocytes and a relative increase in B lymphocytes after irradiation in the patients with mammary carcinoma. On the other hand, Campbell et al 5 found that irradiation caused loss of T cells, B cells, and K cells at similar rates in patients with testicular and ovarian tumors, and long-term depletion of T cells occurred even when the thymus was not irradiated. Khalifa et aP stated that IgA levels were .lower in patients receiving CNS irradiation. We believe that irradiation of CNS is necessary for prevention of CNS leukemia. However, susceptibility to infection after irra-
diation of CNS has been noted; the incidence of infection in irradiated patients is higher than in nonirradiated patients with ALL. Depressed delayed hypersensitivity and depressed antibody production in the irradiated patients are known. Depletion of T and B lymphocytes may induce such immunologic aberrations and increase the risk of infection in children undergoing cranial irradiation for ALL. We acknowledge with thanks the excellent technical assistance of Miss Miyoko Kikutsugi. REFERENCES
1. Fleisher TA, Luckasen JR, Sabad A, Gehrtz RC, and Kersey JH: T and B lymphocyte subpopulations in children, Pediatrics 55:162, 1975. 2. Stjernsward J, Jondal M, Vanky F, Wigzell H, and Sealy R: Lymphopenia and change in distribution of human B and T lymphocytes in peripheral blood induced by irradiation for mammary carcinoma, Lancet 1:1352, 1972. 3. Kataoka Y, and Sado T: The Radiosensitivity of T and B lymphocytes in mice, Immunology 29:121, 1975. 4. Reid MM, Craft AW, and Todd JA: Serial studies of numbers of circulating T and B lymphoeytes in children with acute lymphoblastic leukemia, Arch Dis Child 52:245, 1977. 5. Campbell AC, Wiernik G, Wood J, Hersey P, Waller CA, and Maclennan ICM: Characteristics of the lymphopenia induced by radiotherapy, Clin Exp Immunol 23:200, I976. 6. Khalifa AS, Take H, Cejka J, and Zuelzer WW: Immunoglobulins in acute leukemia in children, J PED]ATR85:788, 1974.
Cranial irradiation and lymphocyte subpopulations in acute lymphocytic leukemia Kunio Kishida, M.D.,* Sumio Miyazaki, M.D., Hiromiehi Take, M.D., Takeo Fujimoto, M.D., Hiroyuki Shin, M.D., Kuniakl Sasaki, M.D., and Nagahide Goya, M.D., Fukuoka, Japan
CRANIAL IRRADIATION was administered to prevent central nervous system involvement in patients with acute lymphocytic leukemia. The numbers of T and B lymphocytes in patients were studied to determine the relative changes. Both T and B lymphocytes were affected by irradiation; B lymphocytes were markedly depleted, but the recovery was more rapid than that of T lymphocytes. From the Department of Pediatrics, Faculty of Medicine, Kyushu University. Supported by grants from the Ministry of Education, Science and Culture and the Ministry of Health and Welfare of Japan. *Reprint address: Departmentof Pediatrics, Facultyof Medicine, Kyushu University,Maidashi, Highashi-ku, Fukuoka 812, Japan.
0022-3476/78/0592-0785500.20/0 9 1978 The C. V. Mosby Co.
Brief clinical and laboratory observations
785
tiated from the usual gram-positive cocci. When gramnegative diplococci are identified, systemic therapy should be instituted in addition to local therapy while awaiting a bacteriologic diagnosis.
REFERENCES 1. Stuart RD, and McWalter D: Primary meningococcal conjunctivitis in children, Lancet 1:246, 1948. 2. Little JM, Centifanto YM, and Kaufman HE: Studies of immunoglobins in human tears, Am J Ophthal 68:898, 1969. 3. Hobart C: Lysozyme in ophthalmic conditions, Am J Ophthal 33:1409, 1950. 4. Gray JDA, and Lambert RA: Meningococcal conjunctivitis, Br Med J 1:17, 1949. 5. Dillman CE: Meningococcemia following meningococcal conjunctivitis, South Med J 60:456, 1967. 6. Newton DA, and Wilson WG: Primary meningococcal conjunctivitis, Pediatrics 60:104, 1977.
MATERIAL AND M E T H O D S Thirty-two children with ALL one to 14 years of age were studied. Both T and B lymphocytes were counted in 14 normal children two and 13 years of age. Initial therapy, for ALL consisted of four to six weeks of vincristine and prednisolone administration. After complete remission was obtained, each child was given cranial irradiation (2,400 rads) during a four- to five-week span in an effort to prevent CNS involvement. Abbreviations used CNS: central nervous system ALL: acute lymphocytic leukemia Lymphocytes were obtained from heparinized venous blood. Leukocyte-rich plasma was incubated with ironcontaining lymphocyte-separating reagent (Technicon Instruments Corporation) for 30 minutes at 37~ 1 The mixture was placed on a Ficoll-Hypaque gradient and centrifuged at 400 g for 45 minutes. The cells at the interface were collected and washed three times with phosphate-buffered saline. The T lymphocytes were identified by the spontaneous sheep red blood cell rosette (E rosette technique); and B lymphocytes by receptors for activated complement (EAC rosette [echnique)? '-' RESULTS The absolute numbers of T and B lymphocytes are shown in the Fig. 1. B lymphocytes fell after cranial irradiation and virtually returned to normal 12 months
786
Brief clinical and laboratory observations
The Journal of Pediatrics May 1978
/mr4 400(
300( O
.
200C
lOOC
,
Complete Remission
,
.
.
.
Radiation
.
3 Mo After Radiation
6 - ~ - ~ 2 Radiation
Mo-'~Tte?" Radiation
Fig. 1. The absolute number ofT and B lymphocytes solid dots; B lymphocytes, open circles; T lymphocytes, dashed fine; normal range derived from controls.
after irradiation. The absolute number of T lymphocytes also fell after radiotherapy, but the decline was proportionately less than that of the B lymphocytes. DISCUSSION These data indicate that both T and B lympbocytes are affected by cranial irradiation. Although B lymphocytes showed greater depression, the recovery was more rapid than that of T lymphocytes. Kataoka et al 3observed that T lymphocytes consisted of two distinct subpopulations with respect to radiosensitivity, and B lymphocytes were extremely sensitive to radiation. Serial studies of numbers of circulating T and B lymphocytes in children with ALL by Reid et aP showed a marked fall in the number of B cells, relatively greater than that of T cells. In other types of malignancy, Stjernsward et al ~ noted a decrease in T lymphocytes and a relative increase in B lymphocytes after irradiation in the patients with mammary carcinoma. On the other hand, Campbell et al 5 found that irradiation caused loss of T cells, B cells, and K cells at similar rates in patients with testicular and ovarian tumors, and long-term depletion of T cells occurred even when the thymus was not irradiated. Khalifa et aP stated that IgA levels were .lower in patients receiving CNS irradiation. We believe that irradiation of CNS is necessary for prevention of CNS leukemia. However, susceptibility to infection after irra-
diation of CNS has been noted; the incidence of infection in irradiated patients is higher than in nonirradiated patients with ALL. Depressed delayed hypersensitivity and depressed antibody production in the irradiated patients are known. Depletion of T and B lymphocytes may induce such immunologic aberrations and increase the risk of infection in children undergoing cranial irradiation for ALL. We acknowledge with thanks the excellent technical assistance of Miss Miyoko Kikutsugi. REFERENCES
1. Fleisher TA, Luckasen JR, Sabad A, Gehrtz RC, and Kersey JH: T and B lymphocyte subpopulations in children, Pediatrics 55:162, 1975. 2. Stjernsward J, Jondal M, Vanky F, Wigzell H, and Sealy R: Lymphopenia and change in distribution of human B and T lymphocytes in peripheral blood induced by irradiation for mammary carcinoma, Lancet 1:1352, 1972. 3. Kataoka Y, and Sado T: The Radiosensitivity of T and B lymphocytes in mice, Immunology 29:121, 1975. 4. Reid MM, Craft AW, and Todd JA: Serial studies of numbers of circulating T and B lymphoeytes in children with acute lymphoblastic leukemia, Arch Dis Child 52:245, 1977. 5. Campbell AC, Wiernik G, Wood J, Hersey P, Waller CA, and Maclennan ICM: Characteristics of the lymphopenia induced by radiotherapy, Clin Exp Immunol 23:200, I976. 6. Khalifa AS, Take H, Cejka J, and Zuelzer WW: Immunoglobulins in acute leukemia in children, J PED]ATR85:788, 1974.