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A patient suffering from chronic immune thrombocytopenia developing B-cell chronic lymphocytic leukemia seventeen years later, is reported. The possible mechanisms of association between the two disorders are discussed.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been reported to induce antitumor activity in peripheral blood monocytes. We examined the role of GM-CSF on bone marrow (BM) macrophages in inducing antibody-dependent cellular cytotoxicity (ADCC) against murine and human tumor cells in vitro and in vivo with the aim of applying this approach in an autologous bone marrow transplantation (BMT) setting. GM- CSF induced a potent ADCC in BM macrophages against a murine melanoma in vitro. Treatment with GM-CSF alone or with antibody alone had no effect, whereas therapy with combination of both these agents resulted in a significant reduction in dissemination of melanoma both in a nontransplant as well as in BMT settings, with results being more optimal in the latter setting. Adoptive transfer of BM macrophages harvested from mice undergoing therapy with GM-CSF plus antibody significantly reduced the dissemination of melanoma in secondary recipients but only after irradiation, not in intact mice. GM-CSF also induced significant ADCC in human BM macrophages against a melanoma and a lymphoma in vitro and against a lymphoma implanted in nude mice in vivo. Again, these effects were more optimal after chemotherapy. These data suggest that treatment with GM-CSF plus tumor-specific monoclonal antibodies after BMT may induce an antitumor effect and help eradicate the minimal residual disease.

Interleukin-2 (IL-2) therapy generates killer cells with major histocompatibility complex (MHC)-unrestricted cytotoxicity against most tumors but not normal tissues. Cyclosporine A (CsA) has been reported to break tolerance to self and to induce killer cells with specificity against class II MHC (Ia) antigens both on the host and the tumor cells, resulting in a mild graft-versus-host disease (GVHD) in an autologous bone marrow transplantation (BMT) setting in the rat. We used these two agents in a syngeneic BMT model in a strain of mice that does not develop GVHD with CsA. Therapy with either agent alone was ineffective, whereas a combination of CsA plus IL-2 after BMT induced a potent graft-versus-tumor (GVT) effect against a melanoma and an acute myeloid leukemia. The antitumor effect could be adoptively transferred by infusing spleen cells harvested from mice treated with CsA plus IL-2 into secondary recipients that received chemoradiotherapy. The cytotoxicity of these cells was not influenced by treatment of tumor cells with gamma-interferon or Ia antibody. The cytotoxic effect was mediated by Thy 1+ and asialo GM 1+ cells. There was no GVHD either in the primary recipients of CsA and IL-2 or in those receiving the adoptively transferred spleen cells. Our findings show that combination therapy with CsA and IL-2 after syngeneic BMT induces a potent GVT effect in a non-MHC-restricted manner, and point to the existence of differences between the mechanisms of GVT and GVHD.

Gonadal functions were evaluated in 92 male patients after treatment for advanced Hodgkin's disease. The patients received six to ten cycles of cyclophosphamide, vincristine, procarbazine, and prednisolone (COPP) chemotherapy. All patients were in remission and were followed for 1 to 17 years (median, 6). Testicular atrophy was noticed in 89 (96.7%) patients. All patients remained azoospermic during the period of follow-up. The testosterone levels did not differ before and after treatment. The follicle stimulating hormone levels rose from pretreatment values (mean +/- standard deviation) of 179.27 +/- 21.99 ng/ml to 578.79 +/- 102.36 ng/ml after the treatment; the rise was significant (P less than 0.001). The luteinizing hormone levels rose from pretreatment values of 106.96 +/- 20.37 ng/ml to 127.37 +/- 32.19 ng/ml after treatment; the rise was significant (P less than 0.05). Testicular biopsy specimens in 19 patients showed germinal aplasia in all cases. It is concluded that six or more cycles of COPP chemotherapy for advanced Hodgkin's disease in men leads to permanent sterility.

Several immunomodulatory approaches have been explored with the aim of inducing a graft versus tumor effect (GVT) in autologous bone marrow transplantation (ABMT). Granulocyte-macrophage colony stimulation factor (GM-CSF) has been reported to induce antibody dependent cellular cytotoxicity (ADCC) via stimulation of peripheral blood neutrophils, lymphocytes, and monocytes. We investigated the role of GM-CSF in inducing ADCC via bone marrow (BM) macrophages against murine and human tumor cells both in vitro and vivo. Our data shows that stimulation of murine BM macrophages with GM-CSF induced a potent ADCC against a murine melanoma in vitro. Treatment of tumor bearing mice with a combination of GM-CSF and antibody against melanoma resulted in a significant reduction in the dissemination of melanoma both in a nontransplant as well as in a transplantation setting. Adoptive transfer of BM macrophages obtained from animals undergoing treatment with GM-CSF plus antibody significantly reduced the spread of tumor in secondary recipients; this effect was seen only in mice undergoing bone marrow transplantation. GM-CSF treatment of human BM macrophages induced a significant ADCC against a human melanoma and a lymphoma in vitro, as well as against a human lymphoma implanted in nude mice. Treatment with GM-CSF alone or with antibody alone was ineffective in controlling the dissemination of tumors both in transplantation as well as in nontransplant situations. These observations indicate that treatment with GM-CSF plus tumor specific monoclonal antibodies after ABMT may induce a GVT effect and bring about the eradication of residual disease.

Pure red cell aplasia (PRCA) often occurs secondary to drug therapy for rheumatoid arthritis (RA). However, idiopathic PRCA in RA is very rare. Though different immunosuppressive therapies have been tried in the past with variable responses, there has been no case report in adults of favourable response to corticosteroids alone. We report a rare case of PRCA in RA, which responded to steroid therapy. Subsequently, the patient relapsed twice, during the first trimester of consecutive pregnancies. The association of PRCA with RA and pregnancy is discussed.

We observed 50 patients receiving high-dose cisplatin-based chemotherapy in a prospective, randomized double-blind trial. One group received metoclopramide (MCP) alone (total dose, 6 mg/kg), whereas the other group was given dexamethasone (DMS) (total dose, 60 mg) in addition to MCP. The patient characteristics of the two groups were comparable, confirming satisfactory randomization. Multivariate regression analysis failed to show any statistical significance in the antiemetic response between the two treatment groups. However, female patients receiving Adriamycin (Adria Laboratories, Columbus, OH) concurrently and obese persons exhibited more vomiting. The overall antiemetic response rate was 66%. Because the side effects were minimal, a higher dose of MCP is expected to improve emetic control without increasing toxicity. The use of a 36-hour assessment period in our study gave more meaningful data. An exponential increase in the dose of MCP is probably required, with respect to weight, to obtain the same antiemetic efficacy.

Fifteen cases of histologically proven Askin Rosai tumor were treated at Tata Memorial Hospital over a period of 3 years. Patients included 12 men and three women. Clinical features included chest wall mass (14), pain (11), bony involvement (6), fever (4), dyspnoea (4), weight loss (1), cough (1), and hemoptysis (1). Previously treated patients received different treatment protocols, which made evaluation difficult. Of our ten patients who have completed induction therapy, five received vincristine and cyclophosphamide, whereas the other five received more aggressive chemotherapy. Complete remission has been achieved in two and four of these patients, respectively. One patient in each group had recurrence of the disease, in both cases at the local site. Thus, from our preliminary data, we suggest that Askin Rosai tumor should be treated with complete surgical excision followed by an aggressive combination of chemotherapy and local radiotherapy.

The clinical manifestations of angio-immunoblastic lymphadenopathy (AILD) suggest that there is an abnormality in the immune system. Most patients with AILD die from opportunistic infections associated with lymphocyte depletion. As chemotherapy further increases the already high susceptibility of infections, the therapeutic management of AILD is difficult. The achievement of complete remission (CR) by the patient described here using a danazol-based regimen raises the hope that treatment of this disease with a noncytotoxic drug may be possible. The rationale behind and advantages of using danazol are discussed.

The records of 458 patients with acute lymphoblastic leukemia (ALL) have been reviewed. The diagnosis of ALL was based on clinical examination and morphological, cytochemical and immunophenotypic characteristics (20% or more blasts reacting with lymphoid monoclonal antibodies) of blood and/or bone marrow. Blast cells of 6 (1.3%) patients showed positive reaction with Sudan black B (SBB) in the absence of reactivity to any other myeloid markers. Positive reaction with SBB stain cannot be considered specific for myeloid series.