Jacqueline S. Hart

Prognostic significance of pretreatment proliferative activity in adult acute leukemia

A statistical analysis of the prognostic significance of eight pretreatment variables was undertaken for 71 previously untreated adult patients with acute leukemia seen at M. D. Anderson Hospital over a 5 ½‐year period. None of the patients had received any prior therapy. Nearly all of the patients (68 of the 71) were treated with 4‐ or 5‐day courses of arabinosyl‐cytosine alone or in combination with cyclophosphamide, vincristine (oncovin) and prednisone (COAP). The pretreatment variables studied were age at diagnosis, the percent labeling index of the bone marrow leukemic cells, diagnosis, the highest temperature prior to start of treatment, the marrow clot section cellularity and smear differential percent of blasts, percent absolute marrow leukemic cell infiltrate and absolute number of blasts × 103/mm3 in the peripheral blood. Fifty‐one patients had acute myeloblastic leukemia (AML) and 20 patients had acute lymphoblastic leukemia (ALL). Using a statistical regression model approach, the only variables found to be of significant prognostic importance with respect to the probability of complete remission for AML patients were the pretreatment percent labeling index, the age of the patient and the highest temperature prior to start of treatment. Unlike AML, the initial percent labeling index did not appear to be of prognostic significance for ALL patients. AML patients with high labeling indices (≥9%) and young patients in general (especially those less than 40 years old) had the best remission rates. With respect to the length of complete remission and survival for all patients, the only important variables were the pretreatment percent labeling index and the age of the patient, respectively. Once in complete remission, an initially high labeling index was an unfavorable sign with respect to length of remission, regardless of the patients diagnosis. The results of this study are supportive of studies in experimental systems demonstrating the importance of cytokinetic factors in the administration of chemotherapy and suggest that such factors may be of clinical importance in selecting approaches to therapy.

Clinical implications of aneuploid cyto genetic profiles in adult acute leukemia

In a series of 170 adult patients with acute leukemia, sequential cytogenetic studies were conducted during a period which included either the initial and, at times, the terminal phase of the disease, or the relapse and remission phases. On the basis of morphological similarities in the karyotype changes, the patients carrying aneuploid clones were categorized into several profiles of aneuploidy. Analysis of the survival times determined from the time of diagnosis suggested that some of these abnormal cytogenetic profiles may have definite clinical implications.

POMP combination chemotherapy of adult acute leukemia

Eighty‐nine adults with acute leukemia (AML and ALL) were treated with a combination of 6‐mercaptopurine (Purinethol), vincristine (Oncovin), methotrexate, and prednisone [POMP] for remission induction and maintenance. The overall response rate was 53% and the complete remission rate 40%. The median duration of maintained complete remission was 24 weeks. The median survival time for all patients was 7 months. For the patients who responded, the median survival time was 13 months. Age and previous therapy were major factors influencing the response of the patients in this study. Side effects other than myelosuppression resulted in liver function abnormalities, minor gastrointestinal intolerance, and paresthesias. POMP chemotherapy is effective remission induction and maintenance therapy for adults with acute leukemia under the age of 50 and who have not had prior chemotherapy.

Studies of a patient isolator unit and prophylactic antibiotics in cancer chemotherapy. General techniques and preliminary results

A patient isolator unit (Life Island) has been evaluated in 13 patients with neoplastic disease. Three oral nonabsorbable antibiotic regimens were used and the patients were fed sterile food. The combination of vancomycin, paromomycin, polymyxin B and amphotericin B or nystatin was well tolerated and effective. Most patients tolerated confinement in the unit quite well, although four very ill patients developed mental aberrations. Weight loss occurred in most patients but was largely due to toxicity from cancer chemotherapy. Infections did occur in the unit but the incidence was lower than would be anticipated. Five of nine patients with acute myelogenous leukemia achieved complete marrow remission and one achieved a partial remission. Three patients in the unit were able to tolerate more intensive chemotherapy than has been customarily given.

A preliminary study of polyamines in the bone-marrow plasma of adult patients with leukemia

Polyamines (mainly putrescine, spermidine, and spermine) whose biosynthesis is a prerequisite for cell proliferation, are potential indicators of malignant growth. To investigate the mechanism of alterations of polyamine levels in physiological fluids in human cancer, polyamine levels of bone-marrow plasma from adult patients with leukemia were studied. Significant correlations were observed between bone-marrow cellularity and spermidine, between peripheral white blood cell counts and spermidine and spermine, and between absolute blast count and spermidine and spermine among untreated patients with acute leukemia. Untreated patients with chronic leukemia showed significantly elevated levels of polyamines relative to untreated patients with acute leukemia, indicating a higher turnover of bone-marrow cells in chronic leukemia than in acute leukemia. Chemotherapy-treated patients with acute leukemia who were in remission or who did not respond to the agent showed low polyamine levels. Patients who showed a destruction of tumor cell during chemotherapy gave high levels of polyamines. Overall, these studies indicate that elevated polyamine levels are markers of cell death.

Current Status of Therapy for Acute Leukemia

Therapy for acute leukemia has improved so rapidly in the last 22 years that many clinical investigators are evaluating therapy regimens designed to be curative rather than merely palliative [1, 2, 3]. For the childhood form of acute lymphoblastic leukemia (ALL) the frequency of induction of at least one complete hematological remission is in excess of 85 per cent. Virtually every child with ALL treated with vincristine and prednisone with or without addition of a drug such as 6-mercaptopurine will demonstrate complete regression of all evidence of disease. This is associated with complete recovery of bone marrow function resulting in normal levels of the formed elements of the blood within 3 to 5 weeks following diagnosis. Chemotherapy has such a high degree of selectivity for the tumor that remission induction can be accomplished with little morbidity and virtually no mortality. The requirements for supportive therapy are minimal in the majority of children. The exceptional failures are recorded only in children with established, irreversible complications such as hemorrhage and infection. Thus, the job of inducing remission of disease for ALL is virtually accomplished.

Acute leukemia in adults, 1977

has been made in the understanding, diagnosis, classification and treatment of acute leukemia. Now known to be a malignant disorder of the blood forming organs, acute leukemia is characterized by progressive accumulation of primi tive blood cells that have lost the capac ity for normal maturation. This accumu lation impairs the production of normal blood elements by the bone marrow, re sulting in anemia, neutropenia, throm bocytopenia and, if uncontrolled by treatment, death usually from infection or hemorrhage. Formerly, the diagnosis of acute leukemia in an adult was fol lowed shortly by death. Today, modem treatment can result in complete remis sion of the disease in most adults, with some patients surviving for prolonged periods of time. Incidence The incidence of acute leukemia steadily increased in this century, until the 1960s, when a leveling off in the rising curve was noted.1 Although much of the increase can be attributed to greater access to medical and diagnostic facili ties, a modest true increase probably oc curred. Ninety percent of patients with acute myelogenous leukemia (AML) are adults, one-third of whom are over 60 years old. However, adults account for only 20 percent of patients with acute lymphoblastic leukemia (ALL). As in other neoplastic diseases, incidence in creases with age.2