ISSN:0001-5792    

DOI:10.1159/000204576

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Patients who undergo autologous bone marrow transplantation (ABMT) for advanced hematologic malignancies experience a high relapse rate. Therapy with interleukin-2 (IL-2) ± lymphokine-activated killer (LAK) cells has induced clinical responses in some patients with advanced malignant lymphoma (ML) or acute myelogenous leukemia (AML). It is postulated that IL-2 ± LAK cells represents a potentially non-cross-resistant therapeutic modality which might prevent or delay relapses if used as consolidative immunotherapy after ABMT, at a time of minimal residual disease. Therefore, we first studied the reconstitu-tion of IL-2-responsive LAK precursor cells after ABMT and found them in the circulation as early as 3 weeks after ABMT. A phase lb clinical trial was then performed which identified a tolerable IL-2 regimen which could be administered early after ABMT and which could induce immunomodulatory effects. We then initiated a clinical trial to determine the feasibility of generating and administering autologous LAK cells using this IL-2 regimen after ABMT for 16 patients with ML. The results show that IL-2 + LAK therapy early after ABMT is feasible but is more toxic than IL-2 alone. Patients with AML on the phase I IL-2 trial and with ML on the IL-2 + LAK protocol were evaluated for tumor status. Of 8 patients with AML in first relapse or at a later stage who underwent ABMT and received IL-2, 2 have relapsed, while 6 remain in complete remission 26+ to 40+ (median 28+) months after ABMT. Of 16 patients with ML considered at high risk for relapse who were treated with ABMT+IL-2+LAK, 5 have relapsed, while 11 remain in complete remission at 6+ to 21+ (median 10+) months after ABMT. The results in both trials are quite encouraging and appear to be better than those in nonrandomized historical controls at our institution. Prospectively randomized trials of IL-2 versus no IL-2 after ABMT in such patients are being initiated to assess definitively the effect, if any, on the relapse rat

ISSN:0001-5792    

DOI:10.1159/000204577

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In childhood idiopathic thrombocytopenic purpura (ITP), both intravenous high-dose steroids and immunoglobulin treatments have been demonstrated to raise platelet counts reliably and in most cases within 72 h, when used as separate therapeutic modalities. However, until now, the preferred emergency management of life-threatening complications in children with ITP has been immediate splenectomy. Since steroids and immunoglobulin create a partial splenic dysfunction, through different mechanisms, we investigated whether combined treatment with both drugs could produce a rapid platelet count increase comparable to that of splenectomy. Eleven patients, ages 4 months to 6 years, with a diagnosis of acute ITP were entered into this pilot study. Treatment consisted of intravenous high-dose methylprednisolone (20 mg/kg in 30 min) followed by intravenous gamma globulin (Gamimune-N, 1 g/kg over 5 h). The combined therapy resulted in rapid increments in the platelet counts of all patients within the 24-hour period. At 12-h, in particular, 9/11 patients had platelet counts of 30 × 109/1 or more. We conclude that this combined therapy provides a prompt rise in platelet counts to a safe and hemostatic level and may offer a viable alternative for emergency splenectomy and its associated morbidity/mortality in many cases of childhood ITP

ISSN:0001-5792    

DOI:10.1159/000204474

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

The use of recombinant human alpha interferon (IFN) to treat relapse of chronic myelogenous leukemia (CML) in chronic phase after bone marrow transplantation (BMT) was studied in a prospective trial. Relapse was defined as > 90% metaphases containing the Philadelphia chromosome (Ph) and hematologic abnormalities consistent with chronic phase CML. In the initial 18 patients, all received allogeneic marrow, 17 from a related donor, 1 from an unrelated donor. Only 1 patient received T-depleted marrow initially. Three patients had relapsed after second BMT. IFN was started at 3 × 106 IU/m2/day and escalated to the maximum tolerated dose or to a maximum of 6 × 106 IU/m7day. Elevated white blood counts and platelet counts were controlled in 14 of 16 and 6 of 6 patients, respectively. Six patients (33%) have had a complete disappearance of the Ph (cytogenetic complete response) and 2 have had a partial response (cyto-genetic partial response < 35% Ph+ 0%) on at least one sample. Six patients had no significant response after 9-12 months and 4 patients developed clinical accelerated phase or blast crisis after 3-6 months. IFN controlled the blood counts in 75% of patients. Of 4 patients with a sex marker, the Ph population was of donor origin in 3 and of host origin in 1. Clonal cytogenetic abnormalities other than the Ph were present in 13 patients and did not predict for lack of response to IFN. IFN effectively produces hematologic control in the majority of patients and suppresses the Ph clone in up to one third. A trial of IFN treatment in an earlier stage of relapse is indicate

ISSN:0001-5792    

DOI:10.1159/000204578

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Recent studies [1, 2] showed that patients with non-Hodgkin’s lymphoma (NHL) with human immunodeficiency virus type 1 (HIV-1) infection may benefit from an intensive chemotherapeutic regimen. We report on our experience in the treatment of NHL-associated HIV-1 infection, with excellent prognostic factors, with MACOP-B regimen [3

ISSN:0001-5792    

DOI:10.1159/000204475

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Phenotypic characterization of peripheral blood lymphocytes was performed in patients with advanced metastatic cancer receiving low-dose recombinant interleukin-2 (rIL-2) and recombinant interferon-α (rIFN-α) as subcutaneous home therapy. A total of 31 patients with progressive metastatic renal cell carcinoma, malignant melanoma, colorectal cancer, B-cell lymphoma, and Hodg-kin’s disease, were evaluated. Patients were treated with a combination of low-dose subcutaneous rIL-2 and rIFN-α, consisting of a 2-day rIL-2 pulse at 9.0 million IU/m2 twice daily, followed by 6 weeks of combined low-dose rIL-2 at 1.8 million IU/m2 twice daily, 5 days per week, and rIFN-α at 5.0 million U/m2 3 times per week. This treatment regimen resulted in an overall significant (p < 0.002) increase in peripheral blood lymphocyte subsets expressing CD3, CD8, CD16, CD25, and CD56. Expansion of peripheral blood natural killer (NK) cells was correlated to treatment response. Thus, treatment-related increase in CD56-positive lymphocytes was 1.8-fold higher in complete or partial responders when compared to progressive disease patients (p = 0.0). Increase in NK cells upon low-dose rIL-2 and rIFN-α was associated with a significant expansion (p = 0.0) of peripheral blood eosinophils (r = 0.71). Patient pretreat-ment using rIL-2, rIL-2 and rIFN-α, or chemotherapy abrogated the treatment-induced induction of NK cells and IL-2 receptor- (CD25) positive T lymphocytes, respectively. Peripheral blood NK cells were significantly decreased (p < 0.05) in patients developing neutralizing antibodies specific t

ISSN:0001-5792    

DOI:10.1159/000204476

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Thirty patients with chronic myeloid leukemia in chronic phase and less than 1 year from diagnosis were treated with a combination of interferon alfa-2a (IFN) 9 million units daily continuously and intermittent low-dose cytosine arabinoside (Ara-C) 20 mg/m2 daily for 21 days every 42 days. The leukemia was controlled initially with hydroxyurea prior to commencing IFN and Ara-C. The treatment was continued for at least 12 months after which time nonresponders were withdrawn from the trial and responders continued on IFN alone. The median duration of follow-up is 14 months (range 10-53 months). Hematolog-ical response was assessed by clinical and laboratory parameters and cytogenetic response was assessed by regular bone marrow chromosome analysis. A complete hematological response occurred in 28/30 patients (93%). A complete cytogenetic response (no detectable Philadelphia chromosome-positive meta-phases) was present on at least one occasion in 9/30 (30%), a partial cytogenetic response (between 1 and 34% Philadelphia chromosome-positive metaphases) in 7/30 (23%) and a minor response in 4/30 (13%), giving an overall cytogenetic response rate of 67%. Significant side effects included mucositis, nausea, cyto-penia and depression. Side effects could be managed by dose reduction or temporary cessation and were tolerable in most patients, but in 1 patient this led to withdrawal from the trial due to severe depression. Two patients have transformed, 1 to acute lymphoblastic leukemia and 1 to accelerated phase. Two patients have died after exiting the study, both from complications of allogeneic bone marrow transplantation. In conclusion, these results are superior to the results using IFN alone and indicate the need for a randomized study.

ISSN:0001-5792    

DOI:10.1159/000204580

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

All-trans-retinoic acid (ATRA) has demonstrated in vivo and in vitro that it could differentiate leukemic cells in acute promyelocytic leukemia (APL). ATRA yields complete remission (CR) rates of approximately 90% in newly diagnosed and first relapsing APL, in APL resistant to one or two courses of chemotherapy, whereas patients in second and subsequent remissions often have only partial remissions. The use of ATRA in APL is associated with two major drawbacks: (1) the risk of rapidly rising leukocyte counts, leading to the ‘retinoic acid syndrome’ which may be fatal if the increase in leukocytes is not reversed and (2) almost universal relapse, if no intensive chemotherapy is administered after CR achievement. Preliminary results, however, suggest that ATRA followed by intensive chemotherapy has improved the outcome of newly diagnosed APL, by slightly increasing the CR rate but also by reducing the risk of relapse, as compared to chemotherapy al

ISSN:0001-5792    

DOI:10.1159/000204581

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

Fibronectin (FN) expression in six myeloma, two mature B-cell lines, and four T-cell lines was analyzed. All myeloma cell lines expressed FN at various levels, while mature B- and T-cell lines apparently had less FN. Moreover, an extra-medullary plasmacytoma-derived myeloma cell line, KHM7, was found to secrete FN into the culture medium. Fibronectin receptors, VLA4 or VLA5, were expressed at various levels on all myeloma cell lines. An adhesion assay revealed three of six myeloma cell lines bound to FN. However, there was no correlation between binding to FN and FN receptor expression, indicating a complicated FN binding pathway. The mechanism and pathological significance of FN expression and FN binding in myeloma cells are discussed.

ISSN:0001-5792    

DOI:10.1159/000204478

出版商:S. Karger AG    

年代:1993

数据来源: Karger

摘要:

In cutaneous T-cell lymphomas (CTCL; mycosis fungoides and Sézary syndrome), the standard therapies tend to be effective but not curative. Single drug therapy with either interferon-α or retinoids shows a response rate of about 45%. In this article, we report the results obtained in the treatment of CTCL with a combined therapy. To date, four clinical studies have been carried out using a combination of low doses of interferon-α and retinoids for treatment in the early stages of CTCL. The mechanism of action of this combination therapy is unkno

ISSN:0001-5792    

DOI:10.1159/000204582

出版商:S. Karger AG    

年代:1993

数据来源: Karger