Beatrice C. Lampkin

Surface Markers and Prognostic Factors in Acute Lymphoblastic Leukemia

We investigated the surface markers on lymphoblasts from 37 patients with acute lymphoblastic leukemia. Spontaneous rosette formation with sheep erythrocytes (E rosettes) identified T cells and the presence of surface immunoglobulin identified B cells. Eight patients had T-marker lymphoblasts; 28 had no markers (null lymphoblasts), and one patient had B-marker lymphoblasts. The eight patients with T-marker acute lymphoblastic leukemia had massive leukemic infiltration, frequently a mediastinal mass, and a poor prognosis. The T-marker lymphoblasts had a weak or negative periodic acid-Schiff reaction and a very low antigenic stimulation to allogeneic lymphocytes. The association of T-marker lymphoblasts and some of the conventional poor-risk factors appears to be reliable in predicting a poor prognosis.

Biological significance of cell cycle kinetics in 128 standard risk newly diagnosed patients with acute myelocytic leukaemia

Bromodeoxyuridine (BrdU) was administered to 128 newly diagnosed patients with standard risk acute myelocytic leukaemia (AML) for cell cycle measurements. Labelling indices (LI) were obtained from both the bone marrow aspirate (BMasp) and biopsies (bx) and durations of S‐phase (Ts) and total cell cycle time (Tc) were measured by double‐labelling the S‐phase cells in vitro with tritiated thymidine. Median LI BMasp was 8% and from BMbx was 25%. The median Ts was 12 h (range 3·1–35 h) and Tc was 48 h (range 11·5–211 h). All patients received induction therapy with a combination of cytosine arabinoside and an anthracycline. Outcome of therapy or FAB type were not related to cell cycle characteristics. Patients with above median LI BMasp, however, had longer remission durations (P= 0·03) as did patients with above median Ts (P= 0·03) and Tc (P= 0·03). Upon longer follow‐ups, even some of the patients with slowly cycling myeloblasts have relapsed (log rank P= 0·453 and 0·203 for Ts and Tc respectively). We conclude that patients with rapidly cycling cells tend to relapse faster; however, slowly cycling nature of myeloblasts is not associated with curability.

Contribution of in vivo proliferation/differentiation studies toward the development of a combined functional and morphologic system of classification of neoplastic diseases.

Proliferation kinetics of both leukemia and a variety of solid tumors have been assessed after in vivo infusions of the thymidine analogues, iododeoxyuridine (IUdR) and bromodeoxyuridine (BrdU). In acute myeloid leukemia (AML), these data indicate that the pretherapy cell cycle time (Tc) of myeloblasts is a prognostic indicator for remission duration since patients with slowly cycling myeloblasts had more durable remissions. The presence of in vivo differentiation detected from the day 7 biopsy after chemotherapy was also of favorable prognosis as these individuals had statistically significant improvement in their remission duration. The data in solid tumors are not mature enough for determining their clinical significance. Since cell kinetic information is readily available in a prompt fashion using these novel techniques, data can be used to plan therapeutic strategies for patients. This review discusses the state‐of‐the‐art techniques available for cell cycle kinetic studies and the clinical and prognostic utility of data that have been generated thus far. Cancer 1992; 69:1557‐1566.

Maintenance therapy in acute childhood leukemia

Thirty-seven children with acute leukemia received as maintenance therapy methotrexate given intravenously every 2 weeks. Nineteen patients received the drug in a dose of 3 mg. per kilogram and 18 patients received larger doses ranging from 3.5 to 6 mg. per kilogram. The median duration of remission for all patients was 7.7 months. The median duration for the first remission was not significantly different from results in a second remission. Patients receiving the larger dose of therapy had longer remissions but this finding might be, due in part at least to patient selection. With this form of maintenance therapy, good results were achieved with minimal drug toxicity and side effects.

Importance of the Non-Dividing Leukemic Cell *

A study of the characteristics of cell proliferation in acute leukemia has potentially three things to offer. First, we may learn the mechanism by which leukemic cells have an advantageous growth differential with respect to the normal marrow cell population. Second, information may be derived concerning the origin of the leukemic cells with particular reference to the need for continued transformation of a normal cell population. Finally, therapy for acute leukemia has been primarily directed against the parts of the cell cycle related to division, that is the synthesis of DNA and mitosis. Further information concerning the nature of the leukemic cell population may give us better methods of using current therapeutic measures and point the way toward new approaches for therapy.

Indications for and benefits of intensive therapies in treatment of childhood cancers.

There has been a striking improvement in the overall numbers of children and adolescents who become disease‐free and remain disease‐free as a result of intensive therapy as defined today, for the following cancers: acute nonlymphocytic leukemia (ANLL), non‐Hodgkins lymphoma (NHL), poor risk acute lymphocytic leukemia (ALL), osteosarcoma, and Ewings sarcoma. The therapy for each of these tumors, with the exception of osteosarcoma, consisted of combination chemotherapy with or without radiotherapy and was started as soon after diagnosis as possible. Aggressive therapy of osteosarcoma has consisted of surgical removal of lung metastases and chemotherapy. Intensive chemotherapy recently has included the use of high doses of certain drugs such as cytosine arabinoside (Ara‐C), methotrexate, VP‐16–213 and melphalan in the treatment of patients with tumors that are currently difficult to treat. Cancer 58:481‐487, 1986.

54 Congenital Pernicious Anemia with Coexistent Transitory Intestinal Malabsorption of Vitamin B12

Pernicious anemia (PA) with coexistent transitory intestinal malabsorption of vitamin B12 has been documented in adults. This report is the first description of proven transitory selective intestinal malabsorption of vitamin B12 in congenital PA. A vitamin B12 responsive anemia was demonstrated in the patient, a 2 ½-year-old girl, by change in the bone marrow from megaloblastic hyperplasia to normoblastic hyperplasia 48 h after 5 μg of vitamin B12. No intrinsic factor (IF) was found in gastric fluid by in vitro assay before and again 4 and 6 weeks after therapy. Congenital PA was established by the age of the patient, absence of IF in gastric fluid, lack of antibodies to IF and parietal cells, presence of HCl in gastric fluid, and normal gastric biopsy. The xylose tolerance test, 72 h fecal fat determination, upper GI series, and biopsy of the jejunum were normal, but the Schilling test was abnormal with hog IF of known potency on two occasions, indicating selective malabsorption of vitamin B12. Six months after therapy the Schilling test was still abnormal without IF, but was normal with both human and hog IF. This normal absorption with IF after therapy is indicative that selective malabsorption was originally present, probably as a consequence of the vitamin B12 deficiency resulting from IF lack. In patients with abnormal radioactive vitamin B12 absorption tests with administration of IF, coexistent PA must be excluded by demonstration of IF in gastric fluid. (SPR)