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The effect of cytomegalovirus (CMV) infection on the production of growth factors and negative regulators in unstimulated or lipopolysaccharide-stimulated human bone marrow stromal cells was assessed. After 5 days, the constitutive and lipopolysaccharide-stimulated production of growth factors was significantly decreased in CMV-infected compared with uninfected stromal cells. This decrease was noted as early as 72 h after infection and appeared to be strictly related to viral replication. On the other hand, the production of inhibitory factors was increased after CMV infection, and this increased release was detectable as early as 24 h after infection. No modulation in the production of interleukin-10 was observed after CMV infection. These data suggest that CMV disturbs the balanced cytokine network, which controls proliferation and differentiation of hematopoietic progenitors. CMV-induced myelosuppression results from this lack of production of growth factors and excess production of inhibitory factors. [ABSTRACT FROM AUTHOR]

A cross-sectional study of quality of life (QOL) was performed in 98 patients in continued first complete remission (CR) for 1–7.4 years, after inclusion in the AML 8A trial which prospectively compared allogeneic bone marrow transplantation (AlloBMT), autologous BMT (ABMT) and intensive consolidation chemotherapy. Several significant differences between the three treatment groups were observed, on the basis of patient self-reports, with regard to somatic symptoms (mouth sores, cough, hair loss, headache), repeated acute medical problems, physical functioning, role functioning, leisure activities and, above all, sexual functioning. There were also significant differences for overall physical condition, and overall quality of life. For all these parameters, the ranking was uniformly AlloBMT lower than ABMT lower than chemotherapy. These differences remain significant after adjustment for time interval between CR and QOL evaluation, sex or age. These results, confirming a higher risk of permanent impairment of QOL after BMT, may have an impact on medical decisions and warrant further studies. [ABSTRACT FROM AUTHOR]

5-Aza-2′-deoxycytidine combined with either amsacrine or idarubicin has been applied in a treatment protocol for patients with a relapse of acute myeloid or lymphocytic leukemia. Sixty-three patients received 5-Aza-2′-deoxycytidine 125 mg/m² as a 6 h infusion every 12 h for 6 days in combination with either amsacrine 120 mg/m² as a 1 h infusion on days 6 and 7 (n = 30) or idarubicin 12 mg/m² as a 15 mm infusion on days 5, 6 and 7 (n = 33). Twenty-three patients (36.5%) obtained a complete remission (CR); eight of 30 patients treated with amsacrine and 15 of 33 treated with idarubicin. Patients with an interval of more than 1 year between initial diagnosis and start of the protocol achieved CR in 51.4%, compared to 15.4% for patients with an interval of less than 1 year. Patients with normal cytogenetics had a higher CR rate (61%) than those with abnormal cytogenetic findings (15.8%). Digestive tract and hematologic toxicity was prolonged, compared to standard induction schedules. Median disease-free survival was approximately 8 months, with only 20% of patients staying in remission for more than 1 year. 5-Aza-2′-deoxycytidine is a good antileukernic agent with considerable toxicity. Current results merit further investigations in previously untreated leukemia. [ABSTRACT FROM AUTHOR]

The effect of cytomegalovirus (CMV) infectionon the production of growth factors and negative regulators in unstimulated or lipopolysaccharide-stimulated human bone marrow stromal cells was assessed. After 5 days, the constitutive and lipopolysaccharide-stimulated production of growth factors was significantly decreased in CMV-infected compared with uninfected stromal cells. This decrease was noted as early as 72 h after infection and appeared to be strictly related to viral replication. On the other hand, the production of inhibitory factors was increased after CMV infection, and this increased release was detectable as early as 24 h after infection. No modulation in the production of interleukin-10 was observed after CMV infection. These data suggest that CMV disturbs the balanced cytokine network, which controls proliferation and differentiation of hematopoietic progenitors. CMV-induced myelosuppression results from this lack of production of growth factors and excess production of inhibitory factors. [ABSTRACT FROM PUBLISHER]

The therapeutic efficacy of interferon-alpha (IFN-alpha) in the treatment of chronic myeloid leukemia is currently being tested in a number of institutional, interinstitutional, and international trials. There is no doubt that responses are achieved in many patients, and in a small subset complete eradication of clonogenic cells may be possible. However, it has not yet been shown that overall survival of patients treated with IFN-alpha is better than that of those treated with conventional cytoreductive drugs. There are still controversial opinions on problems such as dosages and duration of treatment, combination with cytostatic agents, definition of responses, and relevance of cytogenic and molecular data. An international workshop discussed the data on interferon therapy and attempted to define the role of interferon today in the management of chronic myeloid leukemia. [ABSTRACT FROM AUTHOR]

The therapeutic efficacy of interferon-alpha (IFN-α) in the treatment of chronic myeloid leukemia is currently being tested in a number of institutional, interinstitutional, and international trials. There is no doubt that responses are achieved in many patients, and in a small subset complete eradication of clonogenic cells may be possible. However, it has not yet been shown that overall survival of patients treated with IFN-α is better than that of those treated with conventional cytoreductive drugs. There are still controversial opinions on problems such as dosages and duration of treatment, combination with cytostatic agents, definition of responses, and relevance of cytogenic and molecular data. An international workshop discussed the data on interferon therapy and attempted to define the role of interferon today in the management of chronic myeloid leukemia. [ABSTRACT FROM AUTHOR]

The effects of both 13- cis-and all- trans retinoic acid (RA) on colony formation of normal bone marrow (BM) progenitors were investigated in semi-solid (methylcellulose) assays, using either isolated CD 34+ cells or BM mononuclear cells. Single cell liquid cultures were performed to further discriminate between direct and indirect effects. RA action results in significant decrease of colony forming units (CFUs). This effect is more pronounced starting from CD 34+ progenitors than starting from total BM. This overall decrease in CFUs is due to selective inhibition of CFU-M (macrophage) and erythroid colonies (BFU-E). At the single cell level the CFU-M inhibition is confirmed with - in addition - a significant inhibition of CFU-GM (granulocyte-macrophage) and a marked stimulation of CFU-G(granulocyte)s. Both retinoids exert the above-mentioned effects. All- trans RA, however, is effective at a tenfold lower concentration (10 M) than 13- cis RA (10 M). Results on CD 34+ BM fractions (substantially reduced in accessory cells) demonstrate that the described effects can probably be attributed to the direct action of RA on these progenitors; single progenitor (CD 34+) cell liquid cultures further prove this point. [ABSTRACT FROM AUTHOR]

The effects of both 13-cis-and all-trans retinoic acid (RA) on colony formation of normal bone marrow (BM) progenitors were investigated in semi-solid (methylcellulose) assays, using either isolated CD34+ cells or BM mononuclear cells. Single cell liquid cultures were performed to further discriminate between direct and indirect effects. RA action results in significant decrease of colony forming units (CFUs). This effect is more pronounced starting from CD34+ progenitors than starting from total BM. This overall decrease in CFUs is due to selective inhibition of CFU-M (macrophage) and erythroid colonies (BFU-E). At the single cell level the CFU-M inhibition is confirmed with--in addition--a significant inhibition of CFU-GM (granulocyte-macrophage) and a marked stimulation of CFU-G (granulocyte)s. Both retinoids exert the above-mentioned effects. All-trans RA, however, is effective at a tenfold lower concentration (10(-7)M) than 13-cis RA (10(-6)M). Results on CD34+ BM fractions (substantially reduced in accessory cells) demonstrate that the described effects can probably be attributed to the direct action of RA on these progenitors; single progenitor (CD34+) cell liquid cultures further prove this point. [ABSTRACT FROM AUTHOR]

To assess the effects of GM-CSF in patients with myelodysplasia, a total of 101 patients with refractory anemia (RA), RA with ringed sideroblasts (RARS), and RA with an excess of blasts provided that the percentage of blasts in the bone marrow did not exceed 10% (RAEB) were enrolled in the EORTC Leukemia Cooperative Group study 06885. They were randomized to receive two daily subcutaneous injections of rhGM-CSF (mammalian, glycosylated, Sandoz/Schering-Plough) at a daily dose of either 108 micrograms glycoprotein (group I) or 216 micrograms glycoprotein (group II) for 8 weeks. Response was defined as an increase in Hb (greater than 2.5 g%), neutrophil count (more than 100%), or platelet count (more than 100%) without progression of the disease. After exclusion of 19 patients who did not meet the entry criteria, 82 were evaluated. Fifty-four patients (66%) responded (27 of 42 patients in group I and 27 of 40 in group II). Progressive disease was seen in two patients of group I and in four of group II. Two of the latter developed leukemia. All responses were reflected in the granulocytic series. In two patients platelet numbers also increased. Cytogenetic analysis, successfully performed in 43 cases, showed that 14 of 16 patients with normal karyotypes responded, compared with 14 of 27 patients with abnormal karyotypes (p = 0.008). In some cases GM-CSF was reduced in dose or discontinued prematurely due to side effects so that only 35% of all evaluable patients finished 8 weeks of treatment without a change of dose. [ABSTRACT FROM AUTHOR]

Background: B-cell prolymphocytic leukemias or T-cell prolymphocytic leukemias are aggressive variants of chronic lymphoid leukemias. The small studies conducted to date have shown median survival durations of approximately 3 years for patients who have B-cell prolymphocytic leukemia and 7.5 months for those who have T-cell prolymphocytic leukemia, compared with about 8 years for patients who have chronic lymphocytic leukemia. In chronic lymphocytic leukemia, chemotherapy consisting of alkylating agents such as cyclophosphamide and chlorambucil combined with prednisone has achieved overall response rates of 50% to 70%, but this regimen has resulted in response rates of less than 25% in prolymphocytic leukemia. Pentostatin (2'-deoxycoformycin; DCF) is a purine analogue that has shown activity in treatment of chronic lymphoid malignancies.Purpose: This prospective phase II trial by the Leukemia Cooperative Group of the European Organization for Research and Treatment of Cancer was performed to assess the activity and toxicity of DCF in prolymphocytic leukemia.Methods: Twenty patients with B-cell or T-cell prolymphocytic leukemia were given DCF at a dosage of 4 mg/m2 intravenously once a week for 3 weeks, then every other week for three doses. Patients who had at least partial response received maintenance therapy once a month for a maximum of 6 months. Fourteen patients had B-cell prolymphocytic leukemia, and six had T-cell prolymphocytic leukemia, as evidenced by morphologic and immunologic criteria; three were previously untreated, eight had been given one or two chemotherapeutic regimens, and nine had been given more than two.Results: One patient died of an unknown cause during the first 6 weeks of treatment, and one died of disseminated toxoplasmosis during the period of maintenance therapy, 5 months after achieving partial remission. Nine (45% response rate) of the 20 patients achieved partial remission, including seven (50%) of 14 with B-cell prolymphocytic leukemia and two (33%) of six with T-cell prolymphocytic leukemia. The median duration of response was 9 months (range, 2-30 months); for patients with B-cell prolymphocytic leukemia, the median remission duration was 12 months. No complete remission was observed. Toxic effects included nausea and vomiting (30%), infections (30%), and transient increase in liver enzymes (35%) and in creatinine (20%) levels. Eight patients experienced thrombocytopenia, the major hematologic toxic effect; four had grade 3 or 4 toxic effects.Conclusion: DCF is active in prolymphocytic leukemia, even as salvage therapy in patients who had received multiple prior chemotherapeutic regimens.Implications: Trials using DCF or other purine analogues alone or in combination with standard chemotherapeutic agents in front-line or salvage therapy are warranted to improve the prognosis of patients with prolymphocytic leukemia. [ABSTRACT FROM AUTHOR]

Phosphonoformate, ganciclovir, zidovudine and the novel acyclic nucleotide analogues ( S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine [( S)-HPMPA] and ( S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine [( S)-HPMPC] were evaluated for their inhibitory effect on colony forming unit formation by human granulocyte-macrophage progenitor cells (obtained from 11 healthy volunteers) in vitro. The 50 % inhibitory dose of zidovudine, ( S)-HPMPA, ( S)-HPMPC, ganciclovir and phosphonoformate were 10.61, 16.55, 80.88, 41.02 and 668.64 µM, respectively, when the median-effect principle was applied. The bone marrow toxicity of zidovudine used at a low concentration (3.74 µM) was significantly decreased if the drug was combined with ( S)-HPMPA, ( S)-HPMPC or ganciclovir. If used at higher concentrations (74.90 µM), zidovudine showed increased myelotoxicity in the presence of ( S)-HPMPA and ganciclovir, but not ( S)-HPMPC. [ABSTRACT FROM AUTHOR]

Presents a comparative study of myeloid and lymphoid recovery following related, unreleated and allogeneic peripheral stem cell transplantation. Rate and pattern of recovery of granulocytes and lymphocytes; Incidence of opportunistic infections.

A 55-year-old woman with chemotherapy-resistant acute myeloblastic leukemia (AML M2) relapsed 3 months after allogeneic PBSC transplant. The patient was treated with two cycles of low-dose cytarabine chemotherapy followed by G-CSF mobilized donor PBSC after cessation of all immunosuppressive treatment. Hematological and cytogenetic complete remission was observed after the first cycle. The patient had been previously treated for AGVHD after allogeneic PBSC transplantation and experienced a second AGVHD after the second cycles of cytoreductive treatment and donor PBSC infusion. Hematological recovery after donor PBSC infusion was faster than recovery after previous chemotherapy or high-dose chemotherapy. During treatment no febrile neutropenia was observed. This case shows that donor PBSC infusion cannot only provide prolonged complete hematological and cytogenetic remission but also seems to support accelerated hematopoietic recovery for some patients relapsing after allogeneic BMT. [ABSTRACT FROM AUTHOR]

During the last ten years a substantial reduction in mortality has been obtained for Hodgkin's and non-Hodgkin's lymphoma. Since lymphoma treatment is often accompanied by side effects and long-term sequelae, however, patients often have problems with rehabilitation. It is thus very important that these problems and needs be identified. Going back to work is one of the main objectives of rehabilitation and can be taken as a valuable indicator of the problems and needs of such patients. We therefore conducted a study at the Jules Bordet Institute between December 1989 and December 1990. Of the patients in remission and able to go back to work, only 54% of them have done so. Anxiety, depression, and treatment toxicity interfere with return to work, and the likelihood of job reentry increases with the time lapse since the end of treatment. Rehabilitation programs must focus on alleviating illness and treatment sequelae as soon as treatment ends. [ABSTRACT FROM AUTHOR]

The in vitro (H)thymidine-labeling index of bone marrow myeloblasts was determined in eight hematologically normal individuals before and after the administration of Bacillus Calmette-Guérin twice weekly for 2 weeks. The mean labeling indexes of myeloblasts were 30.5 and 45.2% respectively (P<0.004). Further characterization of this stimulation of proliferation of bone marrow myeloblasts could provide some rationale for combining cytotoxic drugs and immunotherapy in cancer patients. [ABSTRACT FROM AUTHOR]