Transplantation of unrelated cord blood cells.

A 43-year-old woman with Philadelphia chromosome (Ph) positive chronic myelogenous leukemia in acute phase received high-dose chemotherapy followed by transfusion of 12 randomly selected units of umbilical cord blood. HLA analysis showed cells of one donor from day +10 to day +43 post-transfusion. This unit was HLA class II identical with that of the patient.

Infusional cisplatin and etoposide in the treatment of stage III-B and IV non-small cell lung cancer: a well tolerated regimen.

Twenty-eight evaluable patients were treated with an infusion of cisplatin and etoposide for advanced non-small cell lung cancer. A response was demonstrated in 43%, although only two patients had documented partial responses. The regimen was surprisingly low in toxicity, both acute and chronic, and is suitable for palliation of patients who are elderly or suffer from chronic illnesses which preclude more agressive therapy.

Reasons for exceeding average length of stay in the terminal patient: one center's experience.

1. LOS was not significantly influenced by the type of insurance carrier. 2. Age was not a factor in LOS of the terminal patient. However, Medicare patients averaged the greatest number of days lost/patient. 3. Terminal Medicare cancer patients whose physician was an oncologist had a shorter LOS. 4. The growing commitment to home hospice will result in a decreasing number of patients coming into the hospital to die. 5. The decreasing number of terminal cancer patients who expire within 72 hours of admission will result in an increase in the average LOS of those remaining hospitalized cancer patients.

Relationship of surveillance cultures to bacteremia and fungemia in bone marrow transplant recipients with Hickman or Broviac catheters.

A total of 64 episodes of bacteremia and fungemia were documented in 25 allogeneic bone marrow transplant recipients. Coagulase-negative staphylococci were the most common pathogens recovered, with 34 of the 39 isolated being methicillin resistant. Streptococcus viridans (11 episodes), diphtheroids (5 episodes), and Pseudomonas aeruginosa (4 episodes) accounted for the majority of the other pathogens causing bacteremia. Six episodes of fungemia were also seen. Coagulase-negative staphylococci were demonstrated in 31 of 36 (86%) throat cultures, 25 of 35 (71%) stool cultures, and 6 of 7 (86%) Hickman or Broviac catheter exit site surveillance cultures prior to the development of bacteremia caused by these organisms. Throat surveillance cultures positive for S. viridans also showed a correlation (88%) with subsequent S. viridans bacteremia. However, surveillance cultures for aerobic gram-negative bacilli, diphtheroids, and fungi did not correlate with subsequent septicemia. Organisms isolated in throat surveillance cultures correlated with subsequent bacteremia caused by these organisms in only 15% of all the cultures taken, while only 14% of stool cultures predicted bacteremia. The utility of surveillance cultures is limited because of low cost-effectiveness and a high rate of false-positive results.

Infectious complications in neutropenic patients. Clinical-laboratory correlations.

Thirty-four patients undergoing bone marrow transplantation or remission induction for acute non-lymphocytic leukemia were the subjects of a study to determine whether outcome of infection (survival, death) could be related to total complement (TC), complement components, or C-reactive protein (CRP). Serum samples were obtained when the neutropenic patients became febrile, and at intervals thereafter. Significant differences were found between final total serum complement levels, the C3 component of complement, and the C-reactive protein. Multivariate logistic regression demonstrated a significant relationship between the final C3 complement and C-reactive protein levels and the outcome of infection. Changes between initial and final values were also predictive of outcome, suggesting that the magnitude and direction of changes in these measurements may assist the clinician in assessing the success of his prescribed antibiotic therapy. Our data suggest that a test battery comprising serial TC, C3, and CRP measurements may have more predictive potential than each test performed independently.

A multicenter trial to document the efficacy and safety of a rapidly excreted analog of hydroxyethyl starch for leukapheresis with a note on steroid stimulation of granulocyte donors.

Currently, the frequency of granulocyte donation is limited by the prolonged circulation of hydroxyethyl starch (HES). We conducted a Phase I, uncontrolled, multicenter trial to evaluate both the efficacy and safety of a rapidly excreted low-molecular-weight analog of HES (LMW-HES). Seventy-five donors underwent 179 centrifugation leukapheresis procedures using LMW-HES as the red-cell-sedimenting agent. The efficacy of LMW-HES was established by harvesting adequate numbers of leukocytes. Most granulocyte concentrates contained at least 20 X 10(9) neutrophils when 8 l of blood was processed from donors optimally stimulated with steroids. The safety of LMW-HES was documented by the detection of almost no clinically significant adverse effects. In only 1.7 percent of procedures did donors require special attention, and only 1 of 179 procedures (0.6%) was permanently discontinued. Results of laboratory studies were usually normal or their values decreased transiently (approximately 15-25%) as a consequence of plasma volume expansion (dilution). Based on previous experience with HES, LMW-HES and HES perform comparably during leukapheresis. When commercially available, use of this new, rapidly excreted analog should permit more frequent leukapheresis donation.

An outbreak of invasive aspergillosis among allogeneic bone marrow transplants: a case-control study.

Between April 1982 and March 1983, 10 of 26 (38.4%) allogeneic bone marrow transplant recipients housed on a newly opened bone marrow transplant unit developed invasive aspergillosis. By contrast, between September 1977 and March 1982, only 3 of 46 (6%) transplant recipients developed invasive aspergillosis. A case-control study to identify host factors related to Aspergillus infection found that aspergillosis was more common in patients with chronic myelogenous leukemia and aplastic anemia, older patients, patients having cytomegalovirus disease, patients who experienced prolonged granulocytopenia, patients conditioned with ara-C (100-200 mg/day), and patients who received longer duration of antimicrobial therapy. A series of logistic regression analyses revealed that underlying disease was the single best predictor of Aspergillus infection. This study demonstrates that underlying disease is an important risk factor for aspergillosis and that special measures may be warranted when transplanting certain patients.

T-cell depletion of bone marrow does not inhibit in vitro hematopoiesis.

One approach to overcome the problem of histoincompatibility in bone marrow transplantation is to use T cell depleted marrow from a haploidentical donor in an attempt to ameliorate graft-versus-host disease. Since the T cell requirements for normal hematopoiesis are uncertain, experiments were performed to study the effects of E rosette-T cell depletion on in vitro growth of hematopoietic progenitor cells. Marrow mononuclear cells were cultured in a modified CFU-GEMM assay before and after T cell depletion. The number of 7 day granulocytic and erythrocytic colonies, and 14 day granulocytic, erythrocytic and mixed colonies were enumerated and expressed in terms of colonies per 10(5) non T cells plated. T cell depletion did not result in decreased proliferation of any of these progenitors save possibly for 14 day granulocytic colonies in one of four experiments. In two cases, T cell depletion resulted in increased growth of progenitor cells. Three of four patients transplanted with T cell depleted haploidentical marrow cells engrafted. It is concluded that E rosette depletion of T cells from marrow does not decrease the potential of these cells to establish hematopoiesis in vitro or in vivo.

Oral manifestations of bone marrow transplantation.

Bone marrow protection by transplantation permits the administration of large doses of antitumor drugs and radiation. Severe oral complications occur in about 70% of patients who have had allogeneic bone marrow transplants and to a lesser degree in patients who have had autologous and syngeneic transplants. Oral complications consist of mucositis, salivary gland dysfunction, loss of resiliency of perioral tissues, periodontal disease, and caries. Pre- and post-transplant oral care aimed at plaque control, control of dental pathology, and hydration of oral tissues are important factors in support therapy of bone marrow transplant patients.

Treatment of myeloid blastic crisis of chronic myelogenous leukemia.

Patients with myeloid blastic crisis of chronic myelogenous leukemia were treated by chemotherapy or by autologous hematopoietic reconstitution after aggressive chemotherapy. Chemotherapy alone failed to produce a second chronic phase. Autologous transplantation resulted in the establishment of a second chronic phase in two of ten patients treated with a four-drug regimen, while treatment with high-dose cytarabine with or without busulfan resulted in the establishment of a second chronic phase in three of six patients and the return of normal hematopoiesis in a fourth. Consolidation chemotherapy appeared to be beneficial.

Oral contraceptives and cancer: a perspective.

PIP: This article argues against widespread use of oral contraceptives (OCs) from 2 perspectives: OC's inpact on the risk of developing certain types of cancers, and the moral issues involved in the pill's abortifacient action. It is predicted that recent studies linking OC use with increased risk of breast and cervical cancer will lead many women to discontinue pill use in favor of sterilization, IUD use, or abortion. It is also anticipated that the pharmaceutical companies will manufacture OCs with a lower hormone content, which will result in a higher failure rate (and a consequent rise in the abortion rate) and produce a greater dependence on the microabortifacient effects of OCs. Promoters of natural family planning are urged to educate couples about the carcinogenic potential of OC use and to point out that there may be further longterm effects not yet manifested. Although contraceptive practice can rarely be influenced by explanations of the ways artificial contraception perverts marital sexuality, explanation of the abortifacient action of OCs and the IUD may be effective among both Catholics and non-Catholics who oppose abortion but see nothing wrong with contraception.^ieng

High-dose cytoreductive therapy with autologous bone marrow transplantation in advanced malignancies.

Twenty-one patients with advanced malignancies received high-dose chemotherapy and/or radiotherapy followed by autologous bone marrow infusion. Eighteen patients (85.7%) had fever greater than or equal to 100 degrees F for a median of 6 days; 14 of these patients required broad-spectrum antibiotics for a median of 13 days. Nineteen patients (90.5%) had a granulocyte count less than 500/mm3 for a median of 11 days. Thrombocytopenia (platelet count less than 50,000/mm3) was observed in 18 patients (85.7%) for a median of 14 days. Mucositis and diarrhea were not common, occurring in six (28.6%) and seven (33.3%) patients, respectively. Of the 21 patients studied, 16 were evaluable for tumor response; there were four complete responses and four partial responses, and two patients who showed no change for variable times. Two patients have unmaintained remissions for greater than 2 years. Our response rate (complete plus partial) is 50%. Our study shows that high-dose cytoreductive therapy can be given with moderate toxicity when combined with autologous bone marrow infusion. Because responses in this group of patients are generally of short duration, we believe that patients with advanced malignancies who have had less exposure to therapy or who have a high likelihood of disease recurrence should be considered for high-dose cytoreductive therapy with autologous transplantation.

An improved method for T-cell depletion of allogeneic histoincompatible donor bone marrow.

Acute graft-versus-host disease (GVHD) following allogeneic bone marrow transplantation is the most significant limiting factor preventing the widespread application of transplant therapy in acute leukemia and aplastic anemia. GVHD is mediated by T cells that contaminate harvested marrow in proportions ranging from 5-50% of the mononuclear cell population. T cell depletion (TCD) of large volumes of human marrow by E-rosetting for 24 h at 4 degrees C with modified sheep erythrocytes achieves removal of greater than or equal to 97% of all T cells, as judged by cytofluorographic analysis of the T-depleted bone marrow population with a broad panel of anti-T cell monoclonal antibodies, and abrogates functional T cell activity. Although T-depleted bone marrow cell recoveries were 2 logs below total harvested buffy coat cell numbers, the TCD mononuclear population was more than 99% viable and was enriched twofold for Ia+ cells as judged by cytofluorographic analysis. This method is at least the equivalent of those employing lectin column or monoclonal antibody/complement lysis techniques and is simpler to perform. Successful engraftment of adult patients can safely be obtained with as few as 4 X 10(8) total mononuclear cells following the 24-h procedure suggesting that prolonged or repeated T-depletion procedures do not interfere with stem cell engraftment. Preliminary results suggest that this method of TCD may ameliorate GVHD in histoincompatible transplants.

Graft-versus-host reaction following blood product transfusion.

The observation of graft-versus-host (GVH) reaction after platelet transfusion in a patient with Hodgkin's disease led us to analyze 38 reported cases in the literature, to outline prognostic factors and to characterize patients at risk. Overall mortality was 68 percent. It was higher among children (76 percent) than among adults (62 percent), and among patients with Hodgkin's disease and immune deficiency syndromes (88 percent) than among those with leukemias (23 percent, p less than 0.005). Following blood transfusions from normal donors, mortality was higher (88 percent) than after transfusions from donors with chronic myelocytic leukemia (25 percent, p less than 0.05). Minimal lymphocyte doses necessary to cause GVH reaction are in excess of 10(7)/kg. Adults seem more resistant to homografts than do children, and the host's cellular immune status is of major prognostic importance. Lymphocytes from donors with chronic myelocytic leukemia may be deficient, and after a threshold dose, the number of lymphocytes transfused does not correlate with clinical outcome. Effective prophylactic measures do exist for this complication but satisfactory therapy does not.