The lung as a target organ in patients with hematologic disorders.

The lung is one of the organs most severely affected by complications during the course of hematologic disorders. In the last years an impressive amount of progress has been made in clarifying the pathogenesis of lung diseases, particularly those occurring in conditions of severe immunosuppression such as bone marrow transplantion, acquired immunodeficiency syndrome or leukemia. Peculiar anatomical characteristics render the lung parenchyma highly susceptible to infections, but the clinical outcome is due not only to the injury induced by the pathogens but also to their interactions with inflammatory cells and particularly to the effects of a wide network of secreted cytokines. Polymorphonuclear cells, macrophages, lymphocytes and structural pulmonary cells (epithelial cells, interstitial cells) generate a variety of cytokines and growth factors which, in turn, may be responsible for the majority of the clinical effects in response to infections, such as those of Pneumocystis carinii and cytomegalovirus, but also to certain drugs or to radiation. The pathogenesis of graft-versus-host disease (GVHD) is still poorly understood, but animal models seem to demonstrate the involvement of a number of cytokines and growth factors, together with toxic effects induced by conditioning regimens.

Clinical implications of serum levels of soluble CD23 and tumor necrosis factor alpha in low-grade non-Hodgkin's lymphoma.

In the last few years the research for new biological features in low-grade non-Hodgkin's lymphoma has provided important results. Several biological parameters are under evaluation and, in particular, cytokines and soluble receptors levels are showing their importance as prognostic parameters. In the present study, serum levels of tumor necrosis factor alpha (TNF-alpha) and soluble CD23 (sCD23) were measured at the time of diagnosis and after induction polychemotherapy in 40 patients with newly diagnosed low-grade non-Hodgkin's lymphoma (LG-NHL). The treatments were CIOP (cyclophosphamide, idarubicin, vincristine, prednisone) regimen for 28 patients and FMP (fludarabine, mitoxantrone, prednisone) scheme for 12 patients. Pretreatment levels of TNF-alpha were highly elevated in patiets with LG-NHL compared with healthy controls (p = 0.005) and were significantly correlated with the Ann Arbor stage (p = 0.001). sCD23 was detected in 35 patients at diagnosis and were markedly increased in LG-NHL patients when compared to healthy controls (p = 0.005); patients with advanced stage presented higher values than those with early stage disease (p = 0.002). All the complete responders (20/40, 50%) showed a decrease of TNF-alpha and sCD23 levels. By contrast, the combination of high levels of TNF-alpha and sCD23 correspond to a group of non-responders. Our results suggest that TNF-alpha and sCD23 are specific prognostic parameters for LG-NHL, and that they could be used as tumor markers within a potential biological prognostic index.

All-trans retinoic acid and in vitro cytokine production by acute promyelocytic leukemia cells.

Leukemic cells spontaneously secrete cytokines involved in the proliferation of the clone; in this study we evaluated the effects of all-trans retinoic acid (ATRA) on the in vitro autocrine production of cytokines by acute myeloid leukemia cells. Thirty acute nonlymphoid leukemia cases (ANLL) (10 APL and 20 ANLL of other cytotypes than APL) were studied; the in vitro secretions of IL-1 alpha, IL-3, IL-4, IL-6, IL-10, G-CSF, GM-CSF, TNF-alpha were tested with and without ATRA addition. After 5 d exposure to ATRA 10(-6) M APL-treated samples showed a significant reduction of IL-6 (p = 0.008) and GM-CSF (p = 0.03) and a significant increase of IL-1 alpha (p = 0.01) production, if compared to untreated APL samples. No difference was seen in IL-3, IL-10 and IL-4 productions; G-CSF production resulted absent in all but 3 APL cases, in which addition of ATRA determined increase in the production. Interestingly, the 3 G-CSF-producing cases did not obtain clinical remission with ATRA; GM-CSF and IL-6 were spontaneously produced by all the cases, and 7 of 10 APL patients subsequently obtained complete remission after induction. TNF-alpha was produced only in 1 case. No statistical difference was seen in all the productions obtained from other than promyelocytic acute leukemic cells, both with and without ATRA addition. However, it is noteworthy that the production of IL-6 was more than twice as high in ANLL non-APL than in APL cases. In conclusion, these data could thus suggest possible complementary mechanisms of the exhaustion of the leukemic clone upon treatment with ATRA.

Limited small cell lung cancer of the lung treated with combination chemotherapy and radiotherapy: a retrospective analysis.

We assessed the outcome in 65 patients with limited small cell lung cancer (SCLC) treated from 1980 through 1989 with combination chemotherapy and chest and cranial irradiation. Of the 65 patients, 32.3% (21/65) achieved a complete remission (CR) prior to radiation therapy; six additional cases achieved a CR after radiotherapy with an improvement of 10% in the incidence of CR. In our group, 8 patients were alive and free of disease at 30 months (12.3%). We think that a combination of local thoracic irradiation in SCLC limited disease plus chemotherapy yields more CR and improves survival, especially in the group of patients who obtained the CR after initial induction chemotherapy.

Mycosis fungoides: a therapeutical review.

In this review of current therapy for mycosis fungoides, the analytical data have been extrapolated from the literature. We have considered the various therapeutic modalities such as topical therapy, photochemotherapy, electron beam radiation therapy, systemic chemotherapy, the combined modalities, as well as the use of interferon and other alternative biological approaches. We conclude with a final section on comments and recommendations that may prove useful in the design of appropriate therapeutic strategies.

Stage I high-grade non-Hodgkin's lymphomas: a retrospective analysis.

BACKGROUND: The treatment strategy for stage I non-Hodgkin's lymphomas (NHL) is far from being clearly established. METHODS: Thirty-seven patients (pts) with clinical stage I high-grade NHL treated between 1983 and 1989 have been retrospectively reviewed. Nineteen pts were treated by radiotherapy (RT) alone; 14 pts received chemotherapy (CT) followed by adjuvant RT, 3 pts CT alone and 1 pt underwent surgery alone. All pts with bulky disease were submitted to combined therapy. RESULTS: Estimated 7-yr overall survival (OS) was 82%, while freedom from relapse (FFR) was 73%. No differences in OS and FFR were recorded with regard to the type of treatment, site of the tumor, sex or histology. CONCLUSIONS: Our conclusion is that stage I NHL, even with unfavourable histology, may be successfully treated with RT only; however, CT before RT may be recommended in pts with a higher risk of relapse, i.e. the presence of bulky mass.

MN (N = Novantrone) COP-B therapy on high and intermediate grade non-Hodgkin's lymphoma: an alternative to MA (A = adriamycin) COP-B?

BACKGROUND AND METHODS: From February, 1987 to August, 1988, fifty-one patients with high and intermediate grade non-Hodgkin's lymphoma (NHL) entered a chemotherapy program MNCOP-B (M = Methotrexate, N = Novantrone, C = Cytoxan, O = Oncovin, P = 6 methyl-prednisolone, B = Bleomycin). Forty patients received MNCOP-B as first-line therapy and 11 patients as salvage therapy after relapse-resistance to other schemes or radiotherapy. RESULTS: The overall remission rate was 51% with a similar distribution of remissions between the two groups under study. At a mean follow-up of 28 months, 20 patients (40%) remain in CR with a disease-free probability of 83% for patients treated with MNCOP-B as up-front therapy and 67% for patients treated with MNCOP-B as salvage therapy. The overall survival at 3 years is 45%; bulky, disease stages III-IV and symptoms are not correlated with poorer survival or a lower remission rate. Patients who received less than 70% of the scheduled doses paradoxically figure better than the others, showing an 87% remission rate, as compared to those who received 100% of the scheduled doses and obtained a 35% remission rate. Major toxicity consisted of mucositis, recorded in 15% and 9% of previously untreated and treated patients, respectively; severe neutropenia was recorded in 27% and 63%, respectively. Despite the number of recorded side effects, only one toxic death due to sepsis occurred. CONCLUSIONS: MNCOP-B is an effective regimen in intermediate and high grade NHL and easily manageable in the out-patient clinic. The incidence of mucositis is sensibly reduced as compared to the parental regimen MACOP-B reported in the literature; this result allows the use of MNCOP-B in older patients.

CEOP regimen in the treatment of advanced low-grade non-Hodgkin's lymphomas: preliminary report.

Between March 1987 and December 1988, 30 previously untreated patients with low-grade non-Hodgkin's lymphomas (NHL), according to the Kiel classification, were treated by a combination of therapy including cyclophosphamide, epirubicin, vincristine, and prednisone (CEOP). Eighteen patients (60%) achieved a complete pathologic remission, and 8 patients (26.6%) had a partial response with a reduction of more than 50% of tumor-related manifestations. Four patients (13.4%) were primary resistant to CEOP. The overall survival was 96.6% with a median follow-up of 25 months from the diagnosis; none of the patients who achieved complete response relapsed at a median follow-up of 21 months from the completion of treatment. Clinical and hematologic toxicities were irrelevant. This regimen was effective in inducing a good remission rate of low-grade NHL, but a longer follow-up for definitive conclusions is warranted.