Gerard Ventura

Stimulation of Myelopoiesis in Patients with Aplastic Anemia by Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor

Aplastic anemia is a syndrome in which pancytopenia occurs in the presence of hypocellularity of the bone marrow. To assess the biologic activities of recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF) in aplastic anemia, we gave GM-CSF (60 to 500 micrograms per square meter of body-surface area) to 10 patients with moderate or severe disease, by continuous intravenous infusion daily for two weeks, and repeated the treatment after a two-week rest period. The treatment increased the white-cell count (1.6- to 10-fold) in all patients, primarily because of an increase in the numbers of neutrophils (1.5 to 20-fold), eosinophils (12- to greater than 70-fold), and monocytes (2- to 32-fold). Rates of hydrogen peroxide production in purified granulocyte fractions increased during GM-CSF treatment. Increases in bone marrow cellularity, myeloid precursor cells, and myeloid:erythroid cell ratios accompanied the white-cell response. Despite the in vivo response of the white-cells, the concentration of colony-forming cells remained the same. Measurable concentrations of interleukin-2 (2 to 15 units per milliliter) were found in the serum of 8 patients, and high levels of erythropoietin (81 to 1200 IU per liter) were found in 10 patients. The predominant side effects were constitutional symptoms. These results indicate that recombinant human GM-CSF is effective in stimulating myelopoiesis in patients with severe aplastic anemia and may benefit some patients in whom the disorder is refractory to standard forms of therapy.

Pneumonia with cunninghamella species in patients with hematologic malignancies: A case report and review of the literature

A patient with chronic myelogenous leukemia in blastic crisis who developed pulmonary and systemic infection with Cunninghamella species is described. The emerging role of this newly recognized pathogen in immunocompromised patients is discussed.

Chemotherapy for resistant and relapsing multiple myeloma

This report summarizes a broad experience in the treatment of patients with multiple myeloma resistant to standard chemotherapy. The VAD regimen has induced remissions in about 50% of relapsing patients but in only about 25% of previously unresponsive patients. In patients resistant to VAD, high‐dose therapies with intravenous melphalan, a CBV combination (cyclophosphamide‐BCNU‐VP‐16) or an EDAP regimen (VP‐16 ‐platinum) produced responses in about 40% of patients. However, these treatments usually required autologous bone marrow or blood stem cell support and the median duration of control was only 6 months. With an even more intensive program using high‐dose melphalan and total body irradiation supported by autologous bone marrow, all patients who survived the early treatment period responded for a median duration of about 1 year. Results indicated a dose‐response effect of chemoradiotherapy on VAD‐resistant myeloma with the potential that such intensive regimens will prolong disease‐free survival time.

Circulating Myeloid Progenitor Cell Kinetics during Hematologic Recovery from Chemotherapy and Subsequent Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor Administration

Hematopoietic recovery from chemotherapy may be associated with an increase in circulating myeloid progenitor cell concentration (CFU-GM); these cells may be harvested by apheresis and used for autologous transplantation after high-dose cytoreductive therapy. Not all patients will demonstrate this increase, possibly due to damage to the stem cell compartment from prior chemoradiotherapy. Elevated circulating CFU-GM has also been reported in patients after short-term administration of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF); whether elevation would persist during longer duration is unknown. We measured circulating CFU-GM (by both limiting dilution in liquid culture and colony formation in semisolid media) in patients with sarcoma who began infusion of rhGM-CSF during recovery from chemotherapy. Patients with elevated circulating CFU-GM did not sustain these levels during subsequent rhGM-CSF infusion. By contrast, patients without rebound elevation of circulating CFU-GM following chemotherapy recovery did increase CFU-GM levels with rhGM-CSF administration. The proportion of marrow CFU-GM in cell cycle during chemotherapy recovery was elevated in both patient groups and remained elevated with rhGM-CSF administration. Both marrow and peripheral blood limiting dilution assays demonstrated linear growth kinetics, indicating a direct effect of the in vitro growth factor (also rhGM-CSF) on progenitor cells without excessive influence or dependence on accessory cells in culture. The use of rhGM-CSF to restore circulating CFU-GM for apheresis during recovery in patients lacking such elevation merits further study.

Collection and Transfusion of Single Donor Platelets and their Clinical Response

The success of transfusing platelet concentrates depends on a variety of factors; those factors are to a certain extent the subject of this paper. The quantity and quality of platelets transfused is discussed in relation to peripheral blood platelet concentration. The data obtained do not yet allow a final conclusion at present, so that further investigations are required.

Peripheral Blood Mononuclear-Stem Cell (PBMSC) Collection in Two Continuous Flow Cell Separators: Yields and Crosscellular Contamination

Interest in PBMSC for autologous transplantation is emerging for patients who are candidates for high-dose chemotherapy and marrow rescue but whose marrow is either fíbrotic or infiltrated with malignant cells. Earlier work described mononu-clear cell concentrate collection from normal donors. Whether the same principles apply to patient who may be pancytopenic is not established. Objectives for collection of PBMSC included: (1) < 10 % granulocytes (PMN); (2) minimal red cells (RBC), and (3) minimal platelet (pit) loss in the patient. Collection was initiated early in the recovery phase from a single dose of Cytoxan, and continued on consecutive weekdays until 7 × 108 PBMnc/kg were collected for 16 multiple myeloma patients using the Spectra (S) or the CS-3000 (CS) for 150 procedures. Mean patient hematocrit was 28%. Mean absolute pre and postprocedure PBMnc was comparable for S and CS; 1.07 ± 9.4/0.9 ± 0.5 × 1071 S, and 1.0 ± 0.6/1.0 ± 0.5 × 109/1 CS: Mean pre/post pit counts differend in S and CS. For S pit were 135 ± 68/114 ± 55 × 109/1, a fall averaging 17%. For CS pit were 127 ± 53/81 ± 50 × 10Vl, a fall averaging 36%. Yields (Y) PBMSC were similar: 6.2 ± 1.8 for S and 6.6 ± 2.5 CS. Yields (Y) RBC and yields (Y) pit differed. For S, yields (Y) RBC and pit were significantly lower: 0.6 × 1011 RBC and 0.99 × 1011 pit. For CS yields (Y) RBC was 1.3 × 10u and yields (Y) pit 3.1 × 10π. Yields (Y) pit was reduced in CS to 2.2 × 10n when centrifugal speeds were reduced and linked to the whole blood processing rates. Collecting too deeply into the RBC and excess myeloma protein resulted in excess PMN contamination for both S and CS. Conclusion: Yields (Y) PBMSC cannot be predicted for either S or CS at this time, and procedural variables must be altered frequently to maintain low crosscellular PMN and RBC contamination for both S and CS. Yields (Y) pit and pit loss in the patient were always less in the S, even after modifying centrifugal speed in CS. Gewinnung peripherer mononuklearer Blutstammzellen (PBMSC) mit zwei Zellseparatoren mit kontinuierlichem Fluß: Ausbeute und Reinheit2 Das Interesse an PBMSC für autologe Transfusionen steigt für Patienten, die Anwärter auf hochdosierte Chemotherapie und Knochenmarkerhaltung sind, deren Knochenmark aber entweder fíbrotisch oder mit malignen Zellen durchsetzt ist. In frü-heren Arbeiten wurde die Gewinnung von mononukleären Zellkonzentraten von normalen Spendern beschrieben. Ob die gleichen Prinzipien auch auf panzytopenische Patienten zutref-fen, ist nicht gesichert. Fakten, auf die man bei Separation von PBMSC achten muß, sind: