New leukemia in the course of therapy of acute lymphoblastic leukemia.

We have recently observed the development of second leukemia of a morphologically different type in three patients with acute lymphoblastic leukemia (ALL) while on therapy. The "second" leukemia occurred while on therapy at 23, 27, and 32 months of initial remission. All three were receiving systemic chemotherapy (CT) and prophylactic fractional irradiation to the central nervous system (CNS). The second leukemias in these three cases were one case of juvenile chronic myelogenous leukemia (JCML) and two cases of acute leukemia of the myeloblastic type by the usual morphologic criteria including the presence of Auer rods in one. In two cases a cytogenetically new clone was detected in the remission marrow 10 and 12 months preceding the overt change in clinical status. These three cases demonstrate that second leukemia occurs in patients with ALL and that some late "relapses" fall into this categpry. The possible etiologic role of modern intensive treatment regimens in the development of second leukemia is discussed.

Cytogenetics of juvenile type chronic granulocytic leukemia.

Cytogenetic examination of bone marrow cells from three patients with juvenile chronic granulocytic leukemia (CGL) showed 46,XX,3p-,11p+ ,t(11p:3p) in one case, 45XY,-E in another, and 45X(X),-C/47,XX,+G in the third. The case with the translocated chromosome originally presented like an acute lymphocytic leukemia (ALL). TAn overt clinical picture of juvenile CGL emerged two and a half years later. Serial study of this case revealed no cytogenetic abnormalities until two years after the diagnosis of ALL, when the translocated chromosome was first observed. Unlike the Ph1 chromosome in adult type CGL, chromosomal abnormalities in juvenile CGL lack specificity, resembling ALL in this respect.

Childhood idiopathic thrombocytopenic purpura.

Idiopathic thrombocytopenia purpura-(ITP) in children is generally a benign, self-limited process with spontaneous recovery occurring within a matter of days or weeks. Management remains somewhat controversial to date, however, and the controversy surrounding the use or nonuse of corticosteroids will no doubt continue until critical data become available. At present, there is little or no evidence to support the claim that steroids shorten the natural course of the disease. Furthermore, evidence that steroids lessen the risk of intracranial hemorrhage is conspicuously lacking. The authors no longer use steroids in ITP; however, if one does elect to use steroids, a selective approach based on an assessment of the severity of the bleeding tendency is recommended.

Long-term cytogenetic studies in acute leukemia of children; the nature of relapse.

Sequential long-term cytogenetic studies in 71 children with acute leukemia were designed to investigate the nature of relapse after prolonged remission. In the overwhelming majority of the cases the findings suggested clonal identity of the leukemic cell population in relapse with that studied at the onset of the disease, notwithstanding considerable karyotypic instability in almost half of the patients. In a small minority an independent origin of the relapse clone could not be excluded on cytogenetic grounds but was considered unlikely, since mechanisms capable of accounting for the changes observed in these patients could be demonstrated in other cases. The persistence of diploid leukemic cells in the presence of an aneuploid subclone was demonstrated in the relapse bone marrow and/or spinal fluid in all active phases of the disease. On this basis the conversion from an aneuploid to a predominantly or exclusively diploid karyotype could be visualized, and a new model of clonal evolution, involving repetitive formation of abnormal karyotypes from a surviving diploid clone could be suggested.

Bilateral interstitial pneumonia in acute lymphoblastic leukemia.

Of 148 children with acute lymphoblastic leukemia (ALL) 34 had bilateral interstitial pneumonia (BIP). Their records were reviewed retrospectively to evaluate the incidence of this pneumonia and delineate the various etiologic factors involved. All but 1 were in remission; 82% of the episodes occurred within the first 6 months, the majority of these occurring during the first 3 months of diagnosis of ALL; 16 were receiving methotrexate (MTX), and 14 were receiving combination chemotherapy with vincristine, prednisone and 6-mercaptopurine (6-Mp) and 4 were on no systemic therapy. Thirty patients with 35 episodes recovered within an average period of 18 days, including clearance of radiologic findings; 4 died. Four had open lung biopsies without complications. There was a single case of pneumocystis carinii infection diagnosed postmortem. Laboratory data and histopathologic findings (of 4 biopsies and 3 remaining autopsies) were suggestive of a viral etiology. The incidence of BIP in ALL at Children's Hospital of Michigan is 22.9% with a mortality rate of 10.3%. The incidence of pneumocystis carinii infection appeared to be low. Hypersensitivity to MTX was not substantiated.

Immunoglobulins in idiopathic thrombocytopenic purpura in childhood.

Levels of immunoglobulins G, A and M were determined in 55 children with idiopathic thrombocytopenic purpura (ITP) (32 acute, 18 chronic and 5 recurrent). Mean IgG levels tended to be low in acute ITP and returned to normal with recovery. In contrast, chronic and recurrent ITP had persistently low IgG and IgA levels. C3 complement levels in 10 cases of acute ITP were normal. Seven patients with chronic ITP had their spleens removed, and IgG and IgA levels tended to rise, while IgM levels decreased in 4 patients after the operation. Low IgA levels observed at the onset of purpura in a child might favor the diagnosis of chronic or recurrent ITP.

Cytogenetic analysis of erythroleukaemia in two children - evidence of nonmalignant nature of erythron.

Serial cytogenetic and cytological studies in 2 cases of erythroleukaemia in children indicated that erythropoiesis is not involved in the malignant process itself, but represents a response caused by unknown stimuli. A good correlation was observed between the percentage of aneuploid cells and blasts in mitosis, thus during the erythroid phase aneuploidy was minimal or absent, while during the myeloblastic phase a high percentage of members of the aneuploid clone was present. An inverse correlation between peripheral normoblast count and haemoglobin level indicated that erythropoiesis was under physiological control. Taken together these observations constitute evidence that, in the cases of erythroleukaemia studied, erythroid cells do not have inherent malignant properties. Cytogenetic analysis offers a tool for differentiating this type of erythroleukaemia from other forms of DiGuglielmo's syndrome.