- Email: [email protected]
Comment on the diagnosis and treatment of leukemia and lymphosarcoma
]une, 1967 The ]ournal of P E D I A T R I C S
1021
Comment on the diagnosis and treatment of leukemia and lympbosarcoma E I ~ S E W H E I ~ E in this issue Canale and Smith describe what may be a new entity which is characterized by an enlargement of the reticuloendothelial system with lymphadenopathy, hepatomegaly, and splenomegaly, and presumed immunological deficiencies, sometimes associated with elevation of the g a m m a globulin. Biopsies of lymph nodes in these patients were variously interpreted as showing lymphosarcoma, Hodgkin's disease, a reticuloendotheliosis, or reactive hyperplasia. Two of the patients were treated for lymphosarcoma on the basis of the pathological diagnoses. If these patients had not been seen in a center devoted to. the study of hematological disorders, the similarity between the patients might have gone unnoted. Whether or not these five patients represent a single and distinct entity is unclear at present; it is clear, however, that good pathologists presented with material from these patients made diagnoses of diseases which in. our present state of knowledge are considered to, be fatal and which call for the use of drugs reserved for use in such fatal diseases as leukemia and lymphdsarcoma. At least two. o.ther entities, have been described in which morphological studies have led to a diagnosis of a presumably fatal disease with a consequent course which proved tiae morphological diagnosis in error. The first of these is the now familiar "congenital leukemia" in a child with trisomy 21. Ross and associates 1 reported on such a child in 1963 as "ineffective regulation of granulopoiesis," and Engel and colleagues 2 have reported three others as "transient leukemia"
and reviewed the literature. Although the pathogenesis of this illness, which is either curable leukemia or an exact morphological copy of such, is not known, it is apparent that some infants with mongolism in whom a diagnosis of acute leukemia is made will recover, with o.r without therapy. Some of these patients have b e e n treated with antimetabolites or cytoxic agents; the last three such patients reported were not so treated. A second example is that reported by Randall and co-workers 3 under the heading "familial myeloproliferative disease." In this instance, nine children within one family developed a syndrome indistinguishable from acute or subacute leukemia. Although this illness proved to be fatal to three of the affected members, the others either recovered after a period of ten or twelve years or have been followed for too short a time to, predict their ultimate outcome. These children were members of a large family and studies of both involved and uninvolved children in the family showed a reduction in the content of leukocyte alkaline phosphatase, suggesting that this inherited disorder might not be fully manifested in some members of the family. Again, had the cases not been recognized as familial, and with our mobile population this is quite possible, they might have been recorded as "cures of leukemia." Indeed, the occurrence of a leukemic picture in children with Down's syndrome and in this family casts some doubt upon the reported "cures of leukemia." In all three of these instances, antimetabolites or cytotoxic agents have: been used for Vol. 70, No. 6, pp. 1021-1022
1 0 2 2 McEl/resh
therapy. In some instances, as in case 5 of the paper by Canale and Smith, antimetabolite therapy has been so efficacious as to require its continuation. In other instances~ the results have been less beneficial than would be anticipated in a patient with such a disorder. In no instance, however, were serious deleterious side effects or fatalities recorded from the use of these agents. Indeed, Canale and Smith reco.rd a fottr-year course of Metho.trexate, surely a near record for the use of this drug; generally, it is used in patients with acute leukemia for much shorter periods of time, since the patients become unresponsive. It has become clear that, although these agents are potentially dangerous, they need not be so, if certain precautions are observed. These drugs are also. useful in the treatment of a number of immune disorders; they have proved to be of value in patients with Coombs positive, acquired hemolytic anemia, lupus erythematosus, nephrosis, and other disorders. The full extent of their usefulness is, as yet, unknown. If the patient has been protected from measles, either by having the illness or having been vaccinated prior to the use of the drugs, and if convalescent-immune chicken pox or herpes zoster serum is available, most of such drugs can be used in both neoplastic and
The Journal o[ Pediatrics June 1967
nonneoplastic disorders with simple observation of the peripheral blood counts. The report by Canale and Smith, together with the others referred to, indicates the occasional difficulty in making a certain diagnosis of leukemia or lymphosarcoma in even the best of medical centers. The report of long-term administration of Methotrexate, together with the use of it and other cytotoxic agents in immune disorders, suggests that they may, after further study, be used with relative safety in neoplastic conditions. In addition, as evidenced by these reports, therapy with Methotrexate, cyclophosphamide (Cytoxan), or 6-mercaptopurine can be instituted by competent physicians for the treatment of presumed but unproved lymphoma or leukemia with reasonable safety. A R T H U R E. l~[C E L F R E S H
REFERENCES
1. Ross, J. D., Moloney, W. C., and Desforges, J. F.: Ineffective regulation of granulopoiesis masquerading as congenital leukemia in a mongoloid child, J. PEDIAT. 63: 1, 1963. 2. Engel, R. R., Hammond, D., Eitzman, D. V., Pearson, I-I., and Krivit, W.: Transient congenital leukemia in seven infants with mongolism, J. PEDIAT.65: 303, 1965. 3. Randall, D. L., Reiquam, C. W., Githens, J. H., and Robinson, A.: Familial myeloproIiferative disease, Am. J. Dis. Child. 110: 479, 1965.
1021
Comment on the diagnosis and treatment of leukemia and lympbosarcoma E I ~ S E W H E I ~ E in this issue Canale and Smith describe what may be a new entity which is characterized by an enlargement of the reticuloendothelial system with lymphadenopathy, hepatomegaly, and splenomegaly, and presumed immunological deficiencies, sometimes associated with elevation of the g a m m a globulin. Biopsies of lymph nodes in these patients were variously interpreted as showing lymphosarcoma, Hodgkin's disease, a reticuloendotheliosis, or reactive hyperplasia. Two of the patients were treated for lymphosarcoma on the basis of the pathological diagnoses. If these patients had not been seen in a center devoted to. the study of hematological disorders, the similarity between the patients might have gone unnoted. Whether or not these five patients represent a single and distinct entity is unclear at present; it is clear, however, that good pathologists presented with material from these patients made diagnoses of diseases which in. our present state of knowledge are considered to, be fatal and which call for the use of drugs reserved for use in such fatal diseases as leukemia and lymphdsarcoma. At least two. o.ther entities, have been described in which morphological studies have led to a diagnosis of a presumably fatal disease with a consequent course which proved tiae morphological diagnosis in error. The first of these is the now familiar "congenital leukemia" in a child with trisomy 21. Ross and associates 1 reported on such a child in 1963 as "ineffective regulation of granulopoiesis," and Engel and colleagues 2 have reported three others as "transient leukemia"
and reviewed the literature. Although the pathogenesis of this illness, which is either curable leukemia or an exact morphological copy of such, is not known, it is apparent that some infants with mongolism in whom a diagnosis of acute leukemia is made will recover, with o.r without therapy. Some of these patients have b e e n treated with antimetabolites or cytoxic agents; the last three such patients reported were not so treated. A second example is that reported by Randall and co-workers 3 under the heading "familial myeloproliferative disease." In this instance, nine children within one family developed a syndrome indistinguishable from acute or subacute leukemia. Although this illness proved to be fatal to three of the affected members, the others either recovered after a period of ten or twelve years or have been followed for too short a time to, predict their ultimate outcome. These children were members of a large family and studies of both involved and uninvolved children in the family showed a reduction in the content of leukocyte alkaline phosphatase, suggesting that this inherited disorder might not be fully manifested in some members of the family. Again, had the cases not been recognized as familial, and with our mobile population this is quite possible, they might have been recorded as "cures of leukemia." Indeed, the occurrence of a leukemic picture in children with Down's syndrome and in this family casts some doubt upon the reported "cures of leukemia." In all three of these instances, antimetabolites or cytotoxic agents have: been used for Vol. 70, No. 6, pp. 1021-1022
1 0 2 2 McEl/resh
therapy. In some instances, as in case 5 of the paper by Canale and Smith, antimetabolite therapy has been so efficacious as to require its continuation. In other instances~ the results have been less beneficial than would be anticipated in a patient with such a disorder. In no instance, however, were serious deleterious side effects or fatalities recorded from the use of these agents. Indeed, Canale and Smith reco.rd a fottr-year course of Metho.trexate, surely a near record for the use of this drug; generally, it is used in patients with acute leukemia for much shorter periods of time, since the patients become unresponsive. It has become clear that, although these agents are potentially dangerous, they need not be so, if certain precautions are observed. These drugs are also. useful in the treatment of a number of immune disorders; they have proved to be of value in patients with Coombs positive, acquired hemolytic anemia, lupus erythematosus, nephrosis, and other disorders. The full extent of their usefulness is, as yet, unknown. If the patient has been protected from measles, either by having the illness or having been vaccinated prior to the use of the drugs, and if convalescent-immune chicken pox or herpes zoster serum is available, most of such drugs can be used in both neoplastic and
The Journal o[ Pediatrics June 1967
nonneoplastic disorders with simple observation of the peripheral blood counts. The report by Canale and Smith, together with the others referred to, indicates the occasional difficulty in making a certain diagnosis of leukemia or lymphosarcoma in even the best of medical centers. The report of long-term administration of Methotrexate, together with the use of it and other cytotoxic agents in immune disorders, suggests that they may, after further study, be used with relative safety in neoplastic conditions. In addition, as evidenced by these reports, therapy with Methotrexate, cyclophosphamide (Cytoxan), or 6-mercaptopurine can be instituted by competent physicians for the treatment of presumed but unproved lymphoma or leukemia with reasonable safety. A R T H U R E. l~[C E L F R E S H
REFERENCES
1. Ross, J. D., Moloney, W. C., and Desforges, J. F.: Ineffective regulation of granulopoiesis masquerading as congenital leukemia in a mongoloid child, J. PEDIAT. 63: 1, 1963. 2. Engel, R. R., Hammond, D., Eitzman, D. V., Pearson, I-I., and Krivit, W.: Transient congenital leukemia in seven infants with mongolism, J. PEDIAT.65: 303, 1965. 3. Randall, D. L., Reiquam, C. W., Githens, J. H., and Robinson, A.: Familial myeloproIiferative disease, Am. J. Dis. Child. 110: 479, 1965.