William H. Knospe

Bone marrow scanning with 52iron (52Fe)—Regeneration and extension of marrow after ablative doses of radiotherapy

Extensively irradiated patients were studied from 0 to 73 months after irradiation by 52Fe bone marrow scanning. Marrow regeneration was observed in most patients after intervals of 12 months or longer. The degree of recovery was not dose‐related and the marrow ablative dose was not defined with doses of 4000–5000 rads. Degree of recovery depended more upon the antomic region and/or sequence of fields treated; the last field treated invariably showed poorer regeneration when recovery was uneven. Active erythropoiesis expanded into distal inactive erythropoietic sites from 3–12 months after irradiation and then decreased thereafter. Blood count cytopenias were almost always restricted to the first year after irradiation.

Studies on the Defective Haematopoietic Microenvironment of Sl/Sld Mice

Summary. Femurs and spleens of both Sl/Sld and +/+ origin were implanted into both Sl/Sld and +/+ hosts. Eight weeks later the +/+ grafts incorporated more radioactive iron than did the Sl/Sld ones. The number of colony forming units (CFU) in the marrow of +/+ femur grafts and in +/+ spleen grafts was several fold greater than that in Sl/Sld grafts. X‐irradiation of femur and spleen donors with 950 R reduced the number of CFU in the grafts to 40–60%, whereas grafts from donors exposed to 2500 R supported no CFU growth at all. The haematopoietic cells in the grafts after 6 weeks were almost entirely of host origin.

Treatment of chronic lymphocytic leukemia using chlorambucil and prednisone with or without cycle-active consolidation chemotherapy .A southeastern cancer study group trial

Patients with untreated chronic lymphocytic leukemia (CLL) received protocol treatment with 6 months of chlorambucil (CB) (30 mg/M2) and prednisone (P) (80 mg/d × 5) every 2 weeks. Complete and partial responders (CR, PR) were then randomized to consolidation with six more courses of CB and P or to four courses of cytosine arabinoside (25 mg/M2 every 12 hours × 8, subcutaneously) and cyclophosphamide (25 mg/M2 every 12 hours × 8, orally) every three weeks. Of the 178 eligible patients entered, 138 (78%) were evaluable for induction therapy which produced a 22% hematologic CR and an overall response rate (CR + PR) of 74%. Eighty‐two patients received adequate consolidation, at the end of which 43 were in CR. No difference was seen in response or survival between the two consolidation treatments. Responders had longer survival than nonresponders (P = 0.0001) even when a 6‐month ‘guarantee time’ was excluded, but there was no survival difference between CR and PR. Thus, intermittent CB and P is a well‐tolerated, useful therapy for CLL but the addition of cyclophosphamide and cytosine arabinoside does not improve results.

Burkitt cell acute lymphoblastic leukemia with partial expression of T-cell markers and subclonal chromosome abnormalities in a man with acquired immunodeficiency syndrome

A 45-year-old white male, bisexual, with a 2-year history of acquired immunodeficiency syndrome (AIDS) prodrome, developed a Burkitt cell-like acute lymphoblastic leukemia (ALL). Marker studies of marrow blasts show an unusual and possibly unique pattern, in that an unequivocal monoclonal B cell leukemia, having K-IgM with HLA-DR and B cell subset antigen (BA-1) expression, was superimposed with a mature suppressor T cell marker profile (pan-T, mature T, and suppressor/cytotoxic T antigens). The leukemic blasts were totally negative for terminal deoxynucleotidyl transferase (TdT), human T cell leukemia-lymphoma virus (HTLV) p19 antigen, and other immunoglobulin isotypes. Chromosome analysis of marrow cells disclosed that 70% of the cells had 47,XY, + 12,t(8;14)(q24;q32) chromosome complement, and 30% of the cells had a 47,XY, + 12,dup1q + (q22-31),t(8;14)(q24;q32). The consistent finding of the specific chromosome rearrangement (8/14 translocation) in all abnormal cells suggests that the cells were derived from a common precursor. With regard to the partial T cell marker expression, the significance of these markers in B cell leukemia is unclear, as is their relation to the additional chromosome abnormalities that apparently developed in the process of clonal evolution.

A randomized clinical trial of remission induction, consolidation, and chemo-immunotherapy maintenance in adult acute myeloblastic leukemia

SummaryThe Southeastern Cancer Study Group conducted a randomized clinical trial in acute myeloblastic leukemia and the blastic phase of chronic myelocytic leukemia to compare: Two induction programs (Schedule A) cytosine arabinoside and 6-thioguanine or (Schedule B) cytosine arabinoside, 6-thioguanine and daunorubicin; two consolidation programs (Schedule C) continuation of induction programs at a reduced dose or (Schedule D) a combination of cyclophosphamide, methotrexate and vincristine; and two maintenance programs — (Schedule E) 1 month of BCG, followed by methotrexate or (Schedule F) methotrexate. Over a 3 year period 372 patients were entered and 295 were judged evaluable. None of 11 patients with blastic phase of chronic myelocytic leukemia responded. There were no significant differences between the schedules in the number of patients with acute myeloblastic leukemia achieving complete remissions (37%, Schedule A vs. 41% Schedule B). The relapse rates on consolidation were similar (43%, Schedule C and 39%, Schedule D). BCG significantly prolonged the duration of first remission following consolidation (P<0.05) from 13.0–23.9 weeks. Survival was not significantly prolonged (92.7 weeks vs. 71.7 weeks). There were no serious complications from BCG therapy.

Normal and aberrant expression of cytokines in neoplastic cells from chronic lymphocytic leukemias

Molecular expression of cytokines and cytokine receptors associated with B-cell growth and differentiation was examined in cells from B-cell chronic lymphocytic leukemia patients using the PCR. These studies were undertaken in order to determine whether a particular cytokine could be associated with leukemic transformation in this disease. The precursor-lymphoid and pro-B, pre-B-cell growth factor, interleukin-7, was found to be expressed in 30 of 30 patients, whereas, it was not expressed in normal donor peripheral blood lymphocytes (0 of 8) or in purified B-cell subsets from normal individuals. IL-1 beta and IL-2 receptors, on the other hand, were expressed by B cells from both normal and B-CLL patients. Other cytokine and cytokine receptors examined were not consistently expressed by all donors. Thus IL-7 was found to be the only cytokine tested that was expressed in CLL cells and not in normal cells.

THE EFFECT OF FETUIN AND OF SPLEEN EXTRACTS ON HEMATOPOIETIC PRECURSORS AND ON DIFFERENTIATED HEMATOPOIETIC CELLS IN IRRADIATED MICE

Injection of extracts from normal mouse spleen tissue into irradiated mice enhance the rate of regeneration of colony forming units (CFU‐S) in the femoral marrow. This effect was most pronounced when spleen extract was injected between 24 hr before and 24 hr after the time of irradiation, and was observed only during the first week after a single injection of extract. Another result of injecting spleen extract was an immediate and transient decrease in the marrow cellularity and particularly in the number of mature myeloid cells in the marrow. Fetuin produced comparable effects on the rate of regeneration of CFU‐S and on the numbers of mature myeloid cells in the marrow.

The Pelger-Huet Anomaly: A New Familial Association with Polydactyly and Trisomy 13 Syndrome

Mikhail Berman, Walter Fried, William Knospe, Section of Haematology, Department of Internal Medicine, Rush Presbyterian St. Luke’s Medical Center, Chicago, IL 60612 (USA The Pelger-Huet (PH) anomaly is an autosomal dominant hereditary trait characterized in the heterozygous state by increased condensation of nuclear chromatin, poor segmentation of granulocytes, and a benign course. Its unique nuclear phenotype suggests an inherited defect in the genetic control of the last postmitotic stage of granulocytic maturation which begins with elongation of nucleus of metamyelocyte. So far no studies have shown any correlation between PH and the specific autosome that carries mutant gene or genes. In one study, linkage was established between PH and an unusual autosomal form of muscular dystrophy [1]. Unfortunately, the latter trait has no chromosomal assignment. In 1981, Aznar and Vaya [2] described an 18-month-old girl with the homozygous form of PH and 6 fingers on one hand and 6 toes on both feet. Poly-

Bone marrow transplantation in leukemia: No longer a last resort

The search for cures for the various forms of cancer has long occupied the forefront of medical research. In leukemia, bone marrow transplantation is effecting cure in more and more types of leukemia and in different stages of the disease. This comprehensive review provides the reader with the background and rationale for transplantation, a description of the procedure itself and the potential complications, and a look at the state of the art.