Immunotherapy of minimal residual disease in conjunction with autologous and allogeneic bone marrow transplantation (BMT).

Recent investigations in animal models of human lymphoid and myeloid leukemia suggest that induction of immune-mediated antitumor effects is feasible at the stage of minimal residual disease (MRD) using allogeneic immunocompetent lymphocytes following initial reconstitution with T cell depletion and/or activation of reconstituting syngeneic or allogeneic immune cells by recombinant interleukin-2 (rIL2). Pilot clinical trials in patients with leukemias and lymphomas at high risk to relapse following autologous bone marrow transplantation (BMT) suggest that beneficial antitumor effects may be achieved at the stage of MRD by home immunotherapy as soon as hematopoietic reconstitution occurs using rIL2 (Cetus) and alpha interferon (Roferon A) (Hoffmann LaRoche). Although results obtained from our open trial seem encouraging, prospective randomized trials and longer observation periods are needed in order to confirm immune-mediated antitumor effects in conjunction with autologous BMT in patients with malignant hematological disorders at high risk to relapse. Likewise, it seems that amplification of anti-leukemia effects following allogeneic BMT is feasible by post-transplant infusion of donor's peripheral blood lymphocytes for prevention and/or treatment of relapse.

Underlying coronary artery disease and successful bone marrow transplantation: a case report.

The cardiovascular risk of concurrent coronary artery disease in patients undergoing bone marrow transplantation (BMT) is not well known. We present a case of a 32-year-old male Hodgkin's disease patient with prior chemotherapy and radiotherapy, who underwent autologous BMT. His underlying single vessel coronary artery disease was well documented and he suffered no post-autologous BMT cardiotoxicity.

Generalized granuloma annulare post autologous bone marrow transplantation in a Hodgkin's disease patient.

A case of generalized granuloma annulare is described in a patient with Hodgkin's disease 3 weeks after autologous bone marrow transplantation (BMT). This is, to our knowledge, the first report of generalized granuloma annulare post-BMT. Immunological pathogenesis is suggested and the association with delayed-type hypersensitivity reaction is discussed.

Hydronephrosis in children after bone marrow transplantation: case reports.

Hydronephrosis post-bone marrow transplantation (BMT) diagnosed in five children, was caused by hemorrhagic cystitis and blood clots in the bladder, congenital uretro-pelvic junction stenosis and ureteral obstruction due to adenoviral infection. Patients received conservative therapy to treat the symptoms. However, hydronephrosis did not change the outcome of BMT. Therefore, we suggest less aggressive procedures to treat children with hydronephrosis.

Invasive fungal sinusitis in patients undergoing bone marrow transplantation.

Invasive fungal sinusitis is becoming increasingly common in patients undergoing BMT. This study was undertaken to evaluate the incidence, presenting symptoms, diagnosis procedures, treatment and outcome of invasive fungal sinusitis. The study population comprised 423 consecutive BMT patients at Hadassah University Hospital from January 1986 to August 1992. Eleven patients (2.6%) developed invasive fungal sinusitis, 8 had underlying hematologic malignancies and 3 severe aplastic anemia (SAA). Median interval between BMT and fungal sinusitis was 22.5 days (range 2-106 days). Eight of 11 patients had protracted neutropenia (median 8 days with median neutrophil count at the time of fungal sinusitis diagnosis of 0.25 x 10(9)/l). Four patients developed GVHD before fungal sinusitis was diagnosed. Presenting symptoms were fever (100%), orbital swelling (63%), facial pain (54%) and nasal congestion (36%). In 8 patients Aspergillus species were isolated (A. flavus in 7, A. quadrilineatus in 1); in 1 patient Candida albicans was isolated and in the other 2 fungal elements were detected histologically (Fusarium and Mucor, respectively). Six of the patients underwent surgical debridement at diagnosis. Three received granulocyte transfusions. All patients received systemic amphotericin B (7 conventional and 4 amphotericin B colloidal dispersion (ABCD)). Only 2 of the 11 patients responded completely to therapy with a follow-up of 15 months. It appears that invasive fungal sinusitis is a potentially fatal complication in immunocompromised patients post-BMT. Current treatment approaches are largely ineffective and new methods of management of this serious problem are needed.

Prevention and treatment of relapse by bone marrow transplantation.

High, myeloablative doses of chemoradiotherapy represent the treatment of choice for a large number of malignant hematological diseases that cannot be successfully treated with conventional chemotherapy. Residual tumor cells following high dose chemotherapy represent the most common treatment failure, resulting in frequent relapse following autologous bone marrow transplantation (ABMT) and even allogeneic bone marrow transplantation (BMT). Graft vs leukemia (GVL) effects mediated by immunocompetent donor lymphocytes represent a major therapeutic potential of allogeneic BMT which results in reduced rate of relapse, especially when immune interactions between immunocompetent donor's T lymphocytes and host allogantigens is apparent, a reaction which might result in graft vs host disease (GVHD). Recent experiments in animal models of murine leukemias suggest that post-transplant immunotherapy may be successfully accomplished by lymphokine-mediated immunotherapy (LMI) and cell-mediated immunotherapy (CMI). Following allogeneic BMT, provided GVHD can be prevented by T-cell depletion, CMI may be amplified by repeated administration of immunocompetent donor's lymphocytes in graded increments following successful induction of chimerism and sustained hematopoiesis. GVL effects induced by CMI may be further potentiated by in-vivo administration of a short course of recombinant human interleukin-2 (rhIL2). Taken together, our data suggest that post-transplant immunotherapy by cytokines and adoptive cell therapy may successfully prevent relapse in patients at high-risk and even result in complete elimination of tumor cells following overt relapse. Thus, immunotherapy may represent an optimal approach for prevention and treatment of minimal residual disease.

Inappropriate antidiuretic hormone secretion (SIADH) preceding skin manifestations of disseminated varicella zoster virus infection post-BMT.

We report the syndrome of inappropriate antidiuretic hormone secretion (SIADH) preceding the development of skin lesions of varicella zoster virus (VZV) infection in a patient with CML 5 months post-allogeneic BMT. This is the first report of SIADH complicating disseminated VZV infection in a BMT patient. SIADH is an unusual complication that may precede VZV infection post-BMT.

Tumor lysis syndrome in nonhematologic malignancies. Report of a case and review of the literature.

Tumor lysis syndrome (TLS), resulting from massive necrosis of neoplastic cells after chemotherapy, is a rare complication in nonhematologic malignancies. A 32-year-old woman suffering from a rapidly progressing breast adenocarcinoma metastatic to the liver and bones received a course of single-agent chemotherapy with mitoxanthrone and 4 days later developed the tumor lysis syndrome, and subsequently acute renal failure. The patient responded well to appropriate treatment. This case report points out that breast cancer can be extremely sensitive to chemotherapy and suggests that prophylaxis for tumor lysis syndrome should be considered in the subset of patients with breast carcinoma who have hepatic metastases and large tumor burdens.

Rhinocerebral aspergillosis in patients undergoing bone marrow transplantation.

Rhinocerebral aspergillosis (RA) is becoming increasingly common in patients undergoing bone marrow transplantation (BMT). The disease can involve nearly all major head and neck structures, including the nose, paranasal sinuses, and orbits. Intracranial extension of the infection is of major concern, since this is usually a fatal complication. Our study population comprised 423 consecutive BMT patients at Hadassah University Hospital from January 1986 to August 1992. Eight patients (1.9%) developed RA, 5 of whom had underlying hematologic malignancies, and 3 of whom had severe aplastic anemia. Only 2 of the 8 patients responded completely to therapy, with a follow-up of 15 months. It appears that RA is a fatal complication in immunocompromised patients post-BMT. Early diagnosis followed by extensive surgical debridement of necrotic tissue and systemic, as well as topical, antifungal therapy with amphotericin B or its new formulations and the patient's recovery of bone marrow function may improve the outcome of this life-threatening complication.

Successful administration of low molecular weight heparin in a patient with heparin-induced thrombocytopenia and coumarin-induced skin necrosis.

A case of heparin-induced thrombocytopenia and skin necrosis induced by coumarin is reported in a 58-year-old female patient suffering from metastatic breast adenocarcinoma and deep vein thrombosis. The thrombosis resolved after treatment with low molecular weight heparin and the thrombocytopenia recovered within a few days. The occurrence of both these rare complications in the same patient has not been previously reported in the literature. We present a review of these complications and their current treatment.

Aspergillus quadrilineatus, a new causative agent of fungal sinusitis.

Aspergillus quadrilineatus was found to be the etiologic agent of pansinusitis in a patient suffering from acute nonlymphoblastic leukemia and who had undergone allogeneic bone marrow transplantation. A. quadrilineatus was cultured from biopsy specimens of the maxillary sinus, and tissue sections with fungal stains showed a necrotic area containing dichotomously branching septate hyphae, which is morphologically consistent with Aspergillus species. The patient was successfully treated with a combination of surgical debridement, granulocyte transfusions, and intravenous administration of amphotericin B-cholesterol sulfate colloidal dispersion. This is the first report of an infection caused by A. quadrilineatus.

Low molecular weight heparin for Hickman catheter--induced thrombosis in thrombocytopenic patients undergoing bone marrow transplantation.

BACKGROUND: Patients with an indwelling central venous catheter are prone to development of thrombotic complications. Thrombocytopenia in patients undergoing bone marrow transplantation (BMT) generally is protracted. The management of thrombosis in thrombocytopenic patients is difficult because heparin and warfarin are relatively contraindicated because of the high risk of major bleeding. Low molecular weight heparin (LMWH) is a new class of antithrombotic drug. Enoxaparin (Rhone Poulenc Rorer, Antony, France) is an LMWH that has been shown to be effective in the treatment and prophylaxis of venous thrombosis. Enoxaparin, with its high antithrombotic to anticoagulant ratio, may be safer than standard heparin in patients at high risk of hemorrhagic complications. METHODS: The authors report the cases of five thrombocytopenic patients, undergoing autologous BMT, in whom venous thrombosis developed related to a Hickman catheter. RESULTS: All the patients were treated with Enoxaparin and recovered promptly without hemorrhagic complications. CONCLUSIONS: The authors suggest that Enoxaparin is an effective drug in treating thrombocytopenic patients in whom acute venous thrombosis develops.

The anti-emetic efficacy and tolerability of tropisetron in patients conditioned with high-dose chemotherapy (with and without total body irradiation) prior to bone marrow transplantation.

Nausea and vomiting are among the most distressing side-effects of chemoradiotherapy. Conditioning protocols for patients undergoing bone marrow transplantation consist of highly emetogenic high-dose chemotherapy with or without total body irradiation. Marked improvement in controlling emesis and nausea was achieved by the introduction of a new class of antiemetic drugs, the 5HT3 serotonin-receptor antagonists. Tropisetron is a highly potent, selective antagonist of 5HT3 receptors. Previous studies have used a single 5-mg dose i.v. of tropisetron to control nausea and vomiting in cancer patients. The present study was undertaken to evaluate the efficacy and safety of a single daily dose of tropisetron in controlling emesis in patients receiving high-dose chemotherapy (with or without total body irradiation) prior to bone marrow transplantation. The anti-emetic efficacy was investigated in a non-homogeneous cohort in a prospective and open study. Of 11 patients evaluated, 9 (81%) showed complete or major control, 1 (9%) minor control and 1 (9%) failed to respond. The most common adverse events reported during the study included diarrhea (46%) and headache (18%), no patients being withdrawn because of side-effects. Our data suggest that a single 5-mg i.v. dose of tropisetron is safe and effective in preventing chemotherapy-induced emesis in patients receiving bone marrow transplantation conditioning. A larger randomized study is warranted to confirm our preliminary results.