Mary Ellen Haggard

Factors influencing survival in pediatric acute leukemia. The SWCCSG experience, 1958–1970

From 1958 through 1970 a total of 1,024 patients was entered on the 7 clinical studies of the Southwest Cancer Chemotherapy Study Group for newly diagnosed cases of acute leukemia. A review of these cases was undertaken to determine the important factors, other than therapy, influencing survival. The most important variables in terms of survival prognosis were found to be age at diagnosis, histologic type of leukemia, and initial peripheral blood leukocyte count. The influence of these variables appeared to persist for at least 5 years following diagnosis. Based on these variables, a simple heuristic approach was taken to define prognostic groups of patients. The patients race, initial platelet count, hemorrhagic status, and enlargement status of liver, spleen, and nodes were of additional prognostic value, but there appeared to be no prognostic significance in the patients sex, initial hemoglobin value, or percent of blast cells in the bone marrow.

Clinical experience in prevention of candidiasis by nystatin in children with acute lymphocytic leukemia

for the prevention of renal oSteodystrophy. In addition, fluid intake was restricted (he was anephric) and an anticholinergic drug was prescribed, both of which probably contributed to the constipation. It is difficult to know which factor played .the major part in the eventual bowel obstruction, but it would seem reasonable to exert due caution when any patient requires chronic usage of aluminum hydroxide. Efforts to lessen constipation, such as liberal fluid intake, use of laxatives, and, if renal function is not compromised, alternate use of magnesium containing antacids may reduce the risk of a fecal impaction. An appropriate history for constipationshould be a part of the ongoing care of these patients while they are receiving antacid therapy.

Superiority of conventional intrathecal methotrexate therapy with maintenance over intensive intrathecal methotrexate therapy, unmaintained, or radiotherapy (2000-2500 rads tumor dose) in treatment for meningeal leukemia.

In the treatment of patients with meningeal leukemia, conventional intrathecal methotrexate therapy followed by maintenance intrathecal methotrexate at intervals of 8 weeks has been shown superior to an intensive, unmaintained intrathecal methotrexate induction regimen, and to neuroaxis radiotherapy, tumor dose 2000‐2500 rads. In each of the treatment regimens, all children completing proscribed therapy achieved complete CNS remission as judged by the return of CSF findings to normal. Median lengths of remission were: maintenance regimen 240 days; intensive induction regimen, 106 days; and radiotherapy, 216 days. Differences were of statistical significance between the maintenance regimen and the intensive regimen (p = 0.001), and between the radiotherapy and intensive regimens (p = 0.01). Maintenance intrathecal therapy appeared to affect favorably the duration of existing marrow remissions; the median time to marrow relapse for patients given maintenance therapy was significantly longer than for those given intensive induction therapy. Toxicity of the chemotherapy regimens was not prohibitive. Radiotherapy was associated with severe myelosuppression, interruptions of systemic therapy, and serious infections, which resulted in death in five children.

Genetic Haemoglobin Abnormalities in about 9000 Black and 7000 White Newborns; Haemoglobin F Dickinson (Aγ97 HisÅg), a New Variant

Summary. Electrophoretically detectable haemoglobin abnormalities are readily identified in umbilical cord blood haemolysates by cellulose acetate electrophoresis, followed by citrate agar electrophoresis of those samples exhibiting an abnormality, and, if necessary, by globin electrophoresis. In samples from 9224 Black newborns, the prevalence of all such abnormalities was about 13%, with 12 cases of sickle‐cell anaemia, seven of Hb‐SC disease and five of Hb‐S β thalassaemia. Clinical and haematologic manifestations of these conditions usually appeared in the first few years of life. The prevalence of sickle‐cell trait was about 7%, Hb‐C trait 2%, and Hb Barts 5%. Several new or rare haemoglobins, both adult and foetal, were found in individual families.

THE RESPONSE OF ACUTE CHILDHOOD LEUKEMIA TO AN INITIAL AND A SECOND COURSE OF PREDNISONE.

In untreated acute childhood leukemia the number, duration, and quality of remissions induced by prednisone when used alone and again for the second time were determined. The remission rates for therapy in 46 children with untreated disease, and in 41 children in relapse for the second time, were 59 per cent and 46 per cent, respectively. The median duration of remission in the untreated patients was 38 days; for patients in relapse it was 35 days. The median time to detect remission was 28 days in each group.

Vincristine in acute leukemia of childhood.

Ninety‐four children with acute leukemia refractory to other forms of chematherapy were treated by three dosage regimens of vincristine. Complete remission occurred in 21.8% of the children experiencing adequate drug trial, with partial remission in 25.4% and bone marrow remission in 37.4%. Rapidity of response was variable with bone marrow remission occurring between the fourteenth and eighty‐fifth day of therapy and optimum response between the twenty‐first and one hundred and thirteenth day. Remissions, lasting only 20‐154 days, on maintenance therapy with vincristine tended to be relatively short‐lived, compared with those maintained by other agents. Toxicity of vincristine proved to be a limiting lactor, requiring alteration of therap in over 25% of the children treated. Vincristine, nevertheless, is firmly established as a valuable agent for the induction of remission in acute leukemia. Continuing studies indicate that the rate of remission reinduction is markedly increased by the combination of vincristine with prednisone.

Long‐term results of reinforcement therapy in children with acute leukemia

A total of 180 children with acute leukemia was randomized to one of two induction regimens: vincristine plus prednisone, or 6‐mercaptopurine plus prednisone. Of 170 patients evaluable for induction therapy, a hematologic remission was achieved in 83% (72/87) on vincristine plus prednisone, and in 93% (77/83) on 6‐mercaptopurine plus prednisone. When hematologic remission was achieved, patients were randomized to one of three maintenance schedules: 6‐mercaptopurine alone, 6‐mercaptopurine plus prednisone for 4 weeks every 3 months, or 6‐mercaptopurine plus prednisone plus vincristine for 4 weeks every 3 months. The durations of hematologic remission were compared from the achievement of hematologic remission to bone marrow relapse. The survival data were presented as an overview of the effect of this initial therapy on duration of survival. There was no statistical difference between the two induction regimens. The most important finding in the comparison of the three maintenance schedules was that reinforcement of 6‐mercaptopurine maintenance therapy with either prednisone or prednisone plus vincristine resulted in significantly longer durations of remission. Vincristine added to prednisone for reinforcement after induction of remission by vincristine plus prednisone did not increase the duration of hematologic remission or survival over prednisone reinforcement alone.

Zinc and growth in patients with sickle cell disease

tion for intensive treatment during this period. The indiscriminate use of high doses of Factor VIII for all elbow hemorrhages in early adolescence is one possibl e response to this situation. However , the problems of the multitransfused hemophiliac patient? make this approach less than ideal, and the selective application of high-dose replacement therapy to those hemorrhages likely to do badly is a more logical solution. We have shown that elbow hemarthroses which present with pain unaccompanied by stiffness, that are tender, and that have lost more ihan 50% of movement are likely to do badly on a dose of 11 to 16 units of Factor VIIl/kg. A delay of more than three hours from the onset of symptoms is also likely to be associated with lack of response. Bleeding into target joints was associated significantly with success when a one-tailed test was used. From our clinical experience we did not expect hemorrhages into target joints to be associated with better than average respons e to an average dose of Factor VIII, and therefore believe that in this situation the use of a one-tailed test is not permissible. We have shown that trauma does not worsen the out!ook for elbow hemorrhages and that delay in treatment UP tO three hours does not appear to increase the risk. This surprising observation does not necessarily mean that delay in treatment is acceptable. The spee d with which bleeding develops is likely to vary from case to case, and early presentation may delay the onset of high-risk features. The age of the patients did not appear to influence response , although a previous study has suggested that hemorrhages increase in severity through adolescence and peak at the age of 14 to 15 years? Forty percent of the hemorrhages associated with two or more of the four poor prognosis factors needed retransfusion, and this group of hemorrhages should provide a fruitful field for studying the effect of higher initial doses of Factor VIII,

Sickle cell anemia in the first 2 years of life

Summary Studies are presented on 54 Negro children with sickle cell anemia, of whom 26 were examined and the diagnosis found before the age of 2 years. In 2 siblings, one studied from birth and the other from the age of 6 weeks, there was no strict correlation between the rise in S hemoglobin, the reciprocal fall in F hemoglobin, and the development of symptoms. Clinical manifestations did not appear in any of the 54 children before 3 months of age. Symptoms were noted, however, either by personal observation or by history in about one half of the patients before the age of 1 year and in three fourths of the patients before 2 years of age. Particularly noteworthy findings were the osteopathy involving, primarily, the metacarpals and proximal phalanges, and the splenomegaly, which in 4 instances was associated with thrombocytopenia.

Sickling, a quantitatively delayed genetic character.

Summary Positive sickling was found in 7 or 8.3% of blood samples from 84 newborn Negro babies, with 3 to 15% of erythrocytes capable of sickling. In free electrophoresis of the hemoglobin of 4 of these 7, the S hemoglobin content ranged from “not demonstrable” to 21%. Blood samples from one baby with sicklemia were studied at birth, 2 weeks, 6 weeks and 7 months respectively, with a progressive increase of sickling erythrocytes of from 13% at birth to 97% at 7 months, and a corresponding increase in S hemoglobin of from about 14 to 50%. Three of the other babies with sicklemia were reexamined at 41/2 to 7 months, at which time almost 100% of the erythrocytes sickled and S hemoglobin values were of the adult order of 40 to 50%. The presence of hemoglobin C trait was detected in the blood of one new-born baby of the 84, with a hemoglobin C content of only 8%. The rarity of sickle cell anemia and the paucity of sickling erythrocytes in young infants are explained by a quantitative delay in the production of S hemoglobin which, like normal adult hemoglobin (and probably hemoglobin C), does not reach adult levels until the age of about 41/2 months.