High-dose melphalan, etoposide, total-body irradiation, and autologous stem-cell reconstitution as consolidation therapy for high-risk Ewing's sarcoma does not improve prognosis.

PURPOSE: To determine whether consolidation therapy with high-dose melphalan, etoposide, and total-body irradiation (TBI) with autologous stem-cell support would improve the prognosis for patients with newly diagnosed metastatic Ewing's sarcoma (ES). PATIENTS AND METHODS: Thirty-two eligible patients with newly diagnosed ES metastatic to bone and/or bone marrow were enrolled onto this study. Treatment was initially comprised of five cycles of induction chemotherapy (cyclophosphamide, doxorubicin, and vincristine alternating with ifosfamide and etoposide) and local control. Peripheral-blood stem-cell collection was performed after the second cycle of chemotherapy, with delay if the bone marrow was persistently involved. If patients had a good response to initial therapy, they proceeded to consolidation therapy with melphalan, etoposide, TBI, and stem-cell support. RESULTS: Of the 32 eligible patients, 23 proceeded to high-dose therapy consolidation. Of the nine patients who did not proceed to consolidation, four were secondary to progressive disease and two were secondary to toxicity. Three patients died from toxicity during the high-dose phase of the therapy. The majority of the patients who underwent high-dose consolidation therapy experienced relapse and died with progressive disease. Two-year event-free survival (EFS) for all eligible patients is 20%. The 2-year post-stem-cell reconstitution EFS for the subset of 23 patients who received consolidation therapy is 24%. Analysis of peripheral-blood stem-cell collections by molecular techniques for minimal residual disease showed contamination of at least some samples by tumor cells in all three patients with available data. CONCLUSION: Consolidation with high-dose melphalan, etoposide, TBI, and autologous stem-cell support failed to improve the probability of EFS in this cohort of patients with newly diagnosed metastatic ES.

Kasabach-Merritt syndrome-associated kaposiform hemangioendothelioma successfully treated with cyclophosphamide, vincristine, and actinomycin D.

PURPOSE: The authors introduced a successful trial of a chemotherapy regimen to treat refractory thrombocytopenia and pain caused by a rare kaposiform hemangioendothelioma that had been refractory to corticosteroids. PATIENT AND METHOD: A 6-year-old Latina girl with diffuse petechiae, constant pain and edema in her right lower extremity, and severe thrombocytopenia was brought for treatment. Physical examination revealed a large mass in the right lower extremity. The surgical specimen resected earlier in Mexico showed kaposiform hemangioendothelioma, an extremely rare vascular tumor that is frequently associated with consumptive coagulopathy and lymphangiomatosis. Corticosteroid therapy in Mexico had been ineffective in controlling the tumor size, pain, or thrombocytopenia. The patient was brought to the United States because of a rapidly enlarging tumor and intractable leg pain, causing inability to ambulate. Laboratory examinations revealed profound thrombocytopenia and evidence of consumptive coagulopathy. Because of the rapidly enlarging lesion, it was decided to give six cycles of a chemotherapy regimen consisting of vincristine, cyclophosphamide, and actinomycin D (VAC). RESULT: The patient responded to the first cycle of chemotherapy with partial reversal of the thrombocytopenia. The additional five cycles of the same chemotherapy regimen resulted in complete resolution of thrombocytopenia and significant improvement of the pain and edema in the right lower extremity. A follow-up imaging study 9 months later revealed a marked decrease in size of the vascular tumor. CONCLUSION: Inoperable kaposiform hemangioendothelioma unresponsive to corticosteroids can be successfully treated with chemotherapy.

Bone marrow examination in patients with AIDS and AIDS-related complex (ARC). Morphologic and in situ hybridization studies.

Bone marrow examinations were performed on 20 patients with acquired immune deficiency syndrome (AIDS) and 39 with AIDS-related complex (ARC). Fever of unknown origin and thrombocytopenia were common in ARC, but anemia and leukopenia were most frequent in AIDS. Changes in stromal cells and perivascular cuffing of plasma cells were found significantly more often in patients with AIDS than in those with ARC. Malignancies were common in both groups. Human immunodeficiency virus (HIV) nucleic acids were detected with the use of a 3H-labeled cDNA probe with an in situ hybridization method in 11 bone marrow samples (three ARC and eight AIDS). Most commonly positive cells were mononucleated, resembling lymphocytes and histiocytes. Endothelial cells, interdigitating reticulum cells, nucleated red blood cells, and immature myeloid cells also had positive results in some instances. The number of HIV-positive cells was not related to the size of the bone biopsies or the clinical diagnoses. The authors postulate that changes in the peripheral blood and bone marrow of these patients may be related to latent persistent infection with HIV.

Identification of eleven human hemoglobin variants by high-performance liquid chromatography: additional data on functional properties and clinical expression.

Eleven abnormal hemoglobins were detected in the course of cord blood screening or in the evaluation of evident hematological problems in individual cases. Identification of the variant in each case was done by high-performance liquid chromatography (HPLC); HPLC provides a rapid, sensitive means for the examination of abnormal hemoglobins. Some of the 11 variants that were identified have been described repeatedly and are included to provide information on the HPLC behavior of tryptic peptides. Others are much rarer. Additional information is provided about the hematological and clinical expression as well as ethnic and geographical distribution of the abnormal hemoglobin.

The immunoinhibitory activities of the lung lavage materials and sera from patients with pulmonary alveolar proteinosis (PAP).

Pulmonary alveolar proteinosis (PAP) is a diffuse pulmonary disease of unknown etiology, characterized by the accumulation of large amounts of amorphous phospholipid containing material in the alveolar spaces. Lavaging the lungs with large amounts of saline to remove the accumulated material results in marked clinical improvement and often complete remission. We have examined theperiperal blood and lung lavage material from 6 PAP patients in an attempt to detect abnormalities of the normal immune response. The complete blood counts and the numbers of T and B lymphocytes and monocytes were normal: the lavage fluids contained large numbers of macrophages, most of which were engorged with the amorphous material, and varying numbers of lymphocytes and polymorphonuclear leukocytes. The lavage material inhibited the blastogenic response of mononuclear cells to mitogens: 3HTdR incorporation in response to stimulation with concanavalin-A and Pokeweed mitogen was inhibited in both allogeneic and autologous cells, while response to phytohemagglutinin stimulation was inhibited only in autologous cells. The sera of the PAP patients inhibited 3HTdR incorporation in response to all three mitogens. Neither the lavage material nor the sera inhibited E-rosette formation, nor were they cytotoxic to allogeneic mononuclear cells. Thus while the peripheral blood monoculear cells from patients with PAP appeared to respond normally in vitro, the sera and lavage material contained substances which inhibited the in vitro response of mononuclear cells toi mitogens by interfering with normal monocyte-lymphocyte interactions. The inhibiting material does not appear to be immunoglobulin.

Acute leukemia in pregnancy: transient neonatal myelosuppression after combination chemotherapy in the mother.

An 18-year-old primagravida received combination chemotherapy with vincristine, prednisone, L-asparaginase, cyclophosphamide, daunomycin, 6-mercaptopurine and central nervous system (CNS) prophylaxis with intrathecal methotrexate and whole-brain irradiation for acute lymphoblastic leukemia (ALL) beginning in the 12th week of pregnancy. Therapy resulted in sustained complete remission of the leukemia and delivery of a normally developed female infant whose immediate neonatal course was complicated by transient severe bone marrow hypoplasia. Our experience confirms the reports of others that intensive chemotherapy can be administered in the last two trimesters of pregnancy without serious teratogenic complications. However, we conclude that such therapy may cause significant myelosuppression in the newborn.

Phase II clinical trial with high-dose methotrexate therapy and citrovorum factor rescue.

One hundred and thirty-four patients with advanced malignant disease were treated with 496 infusions of high-dose methotrexate (HD-MTX) followed by citrovorum factor rescue. Most patients had failed to respond to previous combination chemotherapy. The overall response rate was 29% with 33 partial responses and six complete responses observed in patients with a variety of tumors. Plasma MTX levels were monitored in all patients during each course of therapy in order to identify those patients with delayed plasma MTX clearance. Patients with abnormally slow rates of plasma MTX decay received escalated doses of citrovorum factor rescue in order to prevent drug-induced toxicity. In general, during this study HD-MTX was well-tolerated. Because serious toxicity was neither frequent, severe, nor unpredictable, its use was not limited. HD-MTX should now be evaluated in well-designed controlled clinical trials to compare its antitumor activity to that of conventional- or standard-dose MTX regimens in diseases where HD therapy appears to have efficacy.

Bactericidal capacity of monocytes of newborn infants.

The peripheral leukocytes of newborn infants and of adult volunteers were studied after separation of polymorphonuclear and mononuclear cells. Monocytes were identified and quantitated with the aid of histochemical staining. The in vitro killing capacity of PMN and of monocytes was assayed against Staphylococcus aureus and Escherichia coli. The monocytes of both infants and adults were significantly less active than were their PMN, but the bactericidal capacity did not differ appreciably between newborn and adult cells of either type.

L-asparaginase reinduction and maintenance therapy in previously treated acute lymphocytic leukemia.

Four patients with acute lymphocytic leukemia previously treated with conventional chemotherapy received intramuscular L-asparaginase in combination with other chemotherapy for reinduction and maintenance therapy. These patients received the L-asparaginase for 8, 14, 27, and 34+ months without demonstrating any significant adverse effects. Only 1 of the 4 was clearly resistant to the other chemo-therapy, and 3 of 4 had recurrence of their disease while receiving L-asparaginase. L-asparaginase can be added to reinduction and maintenance regimens of patients resistant to other chemotherapy and is well tolerated for long periods when given intramuscularly weekly with other immunosuppressant agents.