G. Bellesi

Combined surgery and chemotherapy for the treatment of primary gastrointestinal intermediate- or high-grade non-Hodgkin's lymphomas.

Fifty-five consecutive patients with primary gastrointestinal intermediate or high grade non-Hodgkins lymphoma were analysed to assess the efficacy of chemotherapy following surgical tumour resection. Histological subtypes were high grade (n = 18), intermediate grade (n = 36) and unclassified (n = 1). The majority of patients had gastric presentation (71%) and localised disease (84%). Surgery consisted of radical resection in 25 patients (45%) and partial or palliative excision in the remaining cases (22 and 8 respectively). Four subjects died within 3 months of surgery, two patients refused adjuvant chemotherapy and 49 completed the postoperative chemotherapeutic programme. Chemotherapy included either Fi2/74 (adriamycin + vincristine + bleomycin + cyclophosphamide + prednisone) or Fi3/74 (adriamycin + VM26 + bleomycin + cyclophosphamide + prednisone). Excluding the group who underwent radical tumour resection, postoperative chemotherapy induced complete remission in 81% of the remaining 30 patients. The 10-year cause-specific survival for the 53 treated patients was 76% (median follow-up 58 months) with a stable curve plateau after 80 months. Proportional-hazard multivariate statistics showed that survival was influenced by type of surgical resection (P less than 0.05) and stage (P less than 0.05), whereas age, sex and histological subtype were not influential. Our data indicate that chemotherapy following surgical resection of gastrointestinal lesion induces long-term remission in primary gastrointestinal lymphomas.

Abnormalities of in vitro immunoglobulin synthesis by peripheral blood lymphocytes from untreated patients with Hodgkin's disease.

The immunoglobulin-synthesizing activities of peripheral blood mononuclear cells from 57 untreated patients with Hodgkins disease and 47 normal subjects were compared. Cumulative amounts of IgM and IgG synthesized and secreted by unstimulated and pokeweed mitogen-stimulated cells over a 7-d period were determined in a solid-phase radioimmunoassay. Synthesis of IgM in unstimulated cultures and of both IgM and IgG in cultures stimulated with pokeweed mitogen was markedly reduced in patients with Hodgkins disease, whereas the mean level of the spontaneous IgG synthesis was enhanced. The degree and frequency of in vitro abnormalities were not influenced by disease stage or histology. Depression of pokeweed mitogen-induced immunoglobulin synthesis did not correlate with excessive number of monocytes and it was unaffected by removal of phagocytic cells or addition to the cultures of monocytes from normal individuals. On the other hand, monocytes isolated from blood of patients with Hodgkins disease were even more effective than normal monocytes in supporting pokeweed mitogen-induced immunoglobulin synthesis by normal phagocyte-depleted mononuclear cells. Synthesis of both IgM and IgG induced by pokeweed mitogen remained subnormal after addition to patient B cell cultures of autologous irradiated T cells or allogeneic normal T lymphocytes. T cells from patients with Hodgkins disease appeared at least as effective as normal T cells in helping pokeweed mitogen-induced immunoglobulin production by normal B cells. However, when normal T cells were co-cultured with B cells from patients with Hodgkins disease, spontaneous IgG synthesis declined, whereas the addition of patient T cells to normal B cells resulted in an increase of spontaneous IgG synthesis. In patients showing depression of pokeweed mitogen-induced immunoglobulin synthesis the lymphoproliferative response and immunoglobulin synthesis stimulated by Staphylococcus aureus bacteria of the Cowan first strain, a T cell independent B cell mitogen, were also markedly reduced. These studies demonstrate impairment of immunoglobulin synthesis by cultured lymphocytes from untreated patients with Hodgkins disease after stimulation with polyclonal B cell activators and suggest that the in vitro abnormalities may be, at least in part, the result of a preexisting in vivo activation of lymphocytes in Hodgkins disease patients.

A new protocol (MiCEP) for the treatment of intermediate or high-grade non-hodgkin's lymphoma in the elderly

Age has proved to be an important prognostic factor in patients with advanced non-Hodgkin lymphoma (NHL) and these patients require intensive and extensive therapy. Dose-reduction and therapy attenuation have reduced treatment-related toxicity, but have also decreased therapeutic efficacy. Between January 1990 and December 1992, 41 previously untreated patients, 65 years with stage 2-4 intermediate- or high-grade NHL were treated with a new therapeutic scheme which included Mitoxantrone, Etoposide, Cyclophosphamide and Prednisone (MiCEP). Twenty-eight patients achieved a complete remission, ten patients partial remission (overall response rate of 93%) and two cases were resistant. The overall survival was 66% with a median follow-up of 24 months from diagnosis: three patients relapsed after a median period of 7 months. The relapse-free survival was 92% after a median follow-up of 18 months. Blood and other organ toxicity was acceptable and 12% of patients experienced a grade 4 (WHO) neutropenia. In conclusion, MiCEP was effective in inducing a good remission rate with moderate toxic effects in elderly patients with intermediate- or high-grade NHL and appears to be a useful combination to use in this group of patients.

Combined Surgery and Chemotherapy in Primary Gastric Non-Hodgkin's Lymphoma: a Retrospective Study in Sixty-Six Patients

Sixty-six consecutive patients with primary gastric non-Hodgkins lymphoma are reported. All patients underwent surgery which consisted of radical resection in 23 patients (36%) and partial or palliative excision in the remaining 43 cases (36 and 7 respectively). Three patients died before starting chemotherapy, two refused the treatment and 61 completed the postoperative chemotherapeutic programme. We analysed this group of patients in order to assess the efficacy of chemotherapy following surgery. Chemotherapy included either CVP or the original protocols from our institution. Excluding patients who underwent radical resection, postoperative chemotherapy induced complete remission in 87% of the remaining 39 patients. After a median follow-up of 84 months (range 6-216), the 10-year cause-specific survival was 90% with a stable curve plateau after about 25 months. The survival was only influenced by response to therapy (p < 0.0001). The disease-free survival for patients who were not radically resected was 93%. We encountered only two relapses after 15 and 32 months. One of these was local and the other systemic. Our results indicate that chemotherapy following surgery induces long-term remission and survival in primary gastric lymphoma and in particular improves remission and survival, in stage II. In our opinion, surgery may also be fundamental for the treatment of gastric lymphoma in the majority of cases.

Hodgkin's disease in the elderly: a retrospective clinicopathologic study of 61 patients aged over 60 years.

61 cases of Hodgkins disease (HD) with age over sixty years were diagnosed in a series of 387 patients. Mixed cellularity (57.4%) and nodular sclerosis (14.7%) were the most common histologic subtypes. Clinical presentation was characterized by superficial lymphadenopathy (92%) and/or general symptoms (57.4%). Mediastinal involvement was observed in 24.6% of cases, and 24.6% of patients had a primitive infradiaphragmatic presentation. Stage II was the most frequent (47.5%). At the onset of the disease, normal values of hemoglobin and white cells were observed while the platelet count was more variable. Only 3 patients (5%) were given radiotherapy (RT), 3 received chemotherapy (CH) plus RT, and 55 (90%) CH. Severe hematologic toxicity was observed in only 11.1% of cases. Complete remission (CR) was obtained in 37 patients (61%), 10 of whom relapsed. Elderly patients had a 5-year survival rate of 54.9%, while in younger ones it was 76.4% (p less than 0.001). Survival was strongly influenced by the achievement of CR (p less than 0.001), whereas stage, histopathology, systemic symptoms and therapeutic modalities did not correlate significantly.

Treatment of large cell lymphoma in elderly patients with a mitoxantrone, cyclophosphamide, etoposide, and prednisone regimen: long-term follow-up results.

Patients with aggressive non‐Hodgkin lymphoma (NHL) require intensive and extensive therapy, which seems impracticable in elderly patients due to hematologic and extrahematologic toxicity. Consequent dose reduction and therapy attenuation can reduce treatment‐related toxicity but also decreases therapeutic efficacy. Thus, age represents a fundamental prognostic factor that has a profound influence on both therapeutic decisions and patient outcome.

Primary Conjunctival Lymphoma: Response to Chemotherapy in 4 Cases

Primary Conjunctival Lymphoma: Response to Chemotherapy in 4 Cases G. Bellesi S. di Lollo A. Bosi F. Bernardi G. Campana S. Romagnani P.R. Rossi Ferrini G. Bellesi, S. di Lollo, A. Bosi, F. Bernardi, G. Campana, S. Romagnani, P. Rossi Ferrini, Division of Hematology, Ospedale di Careggi, 50129 Florence (Italy) During the last 10 years few studies have been made concerning primary conjunctival malignant lymphoma. We present a report on 4 cases observed at the Division of Hematology of Florence from May 1970 to May 1980. In all the observed cases the conjunctival lymphoid lesion was painless, lengthening occurred in a large part of the fornix, presenting salmon pink colouring and sharply demarcated borders. The hard elastic tissue of the lesion was covered with uninjured conjunctiva; in 1 case the lesion was bilateral. The histophathologic records were evaluated according to the Rappaport and Kiel classifications. In 1 case, immunologic characterization of the biopsy specimen was also performed [4] and showed B cell proliferation. Staging was based particularly on skull and orbit X-rays, brain and orbit computerized axial tomography (2 patients), lymphography and pyelography or abdominal computerized axial tomography and bone marrow evaluation. All these procedures confirmed the conjunctival involvement alone. Irradiation is generally considered the treatment of choice [2, 5]. Some possible complications are cataract, persistent epiphora and ulceration of the cornea. Furthermore, the generalization of Table I. Characteristics of patients and their responses Observation Sex Age Histology Number of Response Maintenance DiseaseRelapse coursestherapyfree, months

Serum Angiotensin-I-Converting Enzyme and Lysozyme Levels in Untreated and Unsplenectomized Patients with Hodgkin’s Disease

Serum angiotensin-I-converting enzyme (S-ACE) is elevated in active sarcoidosis. In Hodgkins disease (HD) there are few reports with different and contrasting results. We studied S-ACE in 23 healthy controls and in 18 untreated and unsplenectomized patients with HD. In the same cases we studied also serum lysozyme. Lysozyme concentration was significantly higher in HD patients compared with normal controls (p less than 0.01) and was independent of stage, systemic symptoms and presence of mediastinal involvement. S-ACE activity in HD patients was lower than in healthy controls, but not significantly. The correlation coefficient between the two enzymes showed that there was no significant correlation both in controls and in patients.

CD4 + T Cells from Lymph Nodes Involved by Hodgkin's Disease Showing Response in Autologous Mixed Lymphocyte Reaction, are Polyclonal.

Thirteen CD4 + T cell clones (TCCs) showing autologous mixed lymphocyte reaction (AMLR) and 12 CD4 + AMLR-negative TCCs derived from involved lymph nodes (LN) of 4 untreated patients with newly-diagnosed Hodgkins disease (HD) were analyzed for some functional activities and for T cell receptor (TCR) gamma and beta gene rearrangement The majority of the AMLR-positive-, but only two AMLR-negative TCCs showed cytolytic potential when assayed by a lectin-dependent assay. In addition, the proportion of clones able to produce interleukin 2 (IL-2) was higher among AMLR-positive- than AMLR-negative TCCs and the amount of IL-2 synthesized by AMLR-positive TCCs was significantly greater than that of AMLR-negative TCCs. In contrast, no difference in the profile of interleukin 4 (IL-4) and interferon-gamma (IFN-γ) production between AMLR-positive- and AMLR-negative TCCs was detected When AMLR-positive TCCs were analysed for their TCR beta and gamma gene rearrangements, a highly heterogeneous pattern was found. More importantly, TCCs derived from the same donor and displaying the same kind of TCR beta and gamma gene rearrangement showed different patterns of rearrangements, suggesting that CD4 + cells from LN involved by HD, displaying such an unusual functional profile, are polyclonal.

Phase II cooperative study with a new alkylating drug, PTT-119, in the treatment of non-Hodgkin's lymphomas

SummaryIn a phase II cooperative study involving eleven Italian haematological units, the efficacy and toxicity of a new alkylating compound, PTT-119, was evaluated in 53 patients with non-Hodgkins lymphoma (NHL). Forty-five of the patients had been previously treated with various regimens of chemotherapy, the remaining eight were at the onset of the disease. PTT-119 was scheduled at 3.0 mg/kg every three weeks for a minimum of three administrations. Seven patients achieved a complete remission (CR), 19 a partial remission (PR); the overall response rate was 49%. The median duration of response was 6 months. Most frequent adverse effects were alopecia, nausea and vomiting and phlebitis due to the drug infusion. Myelosuppression was severe only in patients with bone marrow involvement or who were heavily pretreated. No liver, cardiac or renal toxicity was recorded. These data indicate that PTT-119 is an effective drug in the treatment of NHL; the matter of its non-crossresistance with other alkylating compounds warrants further studies.