High-dose chemotherapy with peripheral blood stem cell support for stage IIIB inflammatory carcinoma of the breast.

The purpose of this study was to determine outcomes for 56 patients with inflammatory breast cancer (IBC) receiving high-dose chemotherapy (HDC) with cyclophosphamide, thiotepa and carboplatin (CTCb) with peripheral blood stem cell (PBSC) support. All patients received the same total amount of chemotherapy but there were differences in the sequence of therapy: 15 received induction chemotherapy, chemotherapy mobilization of PBSC and CTCb after surgery (adjuvant group) while 41 received induction chemotherapy with (n = 17) or without (n = 24) chemotherapy for mobilization of PBSC prior to surgery and CTCb after surgery (neoadjuvant group). Median time from diagnosis to HDC was 5.5 months (range 3.5-12.5). Fifty-one patients (91%) required admission to the hospital following HDC for a median of 11 days (range 5-25). There were two (4%) infectious deaths after HDC. Twenty-four patients (43%) have relapsed at a median of 18 months (range 8-50) from diagnosis resulting in death in 34%. The probabilities of overall (OS) and event-free survival (EFS) at 3 years for all 56 patients were 0.72 and 0.53, respectively, with a median follow-up of 44 months (range 15-76) from diagnosis. There were no differences in OS, EFS or patterns of relapse between patients in the adjuvant or neoadjuvant groups. These sequences of combined modality therapy incorporating HDC are comparable or superior to other intensive approaches for the treatment of IBC. Further improvements will be necessary to decrease systemic recurrences.

Phase I-II evaluation of rapid sequence tandem high-dose melphalan with peripheral blood stem cell support in patients with multiple myeloma.

This study was designed to determine the maximum tolerated dose (MTD) of high-dose melphalan (HDM), with peripheral blood stem cell support, that could be given twice within 90 days to patients with multiple myeloma. Twenty patients received tandem HDM at 160, 180 or 200 mg/m2 and a total of 55 were treated at the estimated MTD of 200 mg/m2. Seventeen of 55 (31%) did not receive cycle 2; six because of low CD34+ cell yields, three because of severe (n = 1) or fatal toxicities (n = 2) and eight for other reasons. The median interval between doses for 38 patients was 70 days (range 41-225). Three of 55 patients (5%) died of treatment-related causes. In patients completing two cycles of HDM, at any dose level, the complete remission rate improved from 15% following cycle 1 to 55% following cycle 2. The probabilities of survival, event-free survival and relapse or progression at 18 months for the 55 patients treated at the MTD were 0.84, 0.76 and 0.20, respectively, with a median follow-up of 19 months (range 9-36) from mobilization chemotherapy. It was concluded that two cycles of HDM, 200 mg/m2, could be administered to approximately 70% of patients under the age of 66 with multiple myeloma in a median interval of 70 days, with improvement in CR rates.

Second attempts at mobilization of peripheral blood stem cells in patients with initial low CD34+ cell yields.

The purpose of this study was to determine the effectiveness of second mobilization strategies in patients who yielded < 2.5 x 10(6) CD34+ PBSC/kg after initial mobilization. Repeat mobilization attempts were made with chemotherapy and G-CSF (n = 61) or G-CSF alone (n = 58) in patients who failed initial mobilization with chemotherapy and G-CSF (n = 92) or G-CSF alone (n = 27). A median of 0.27 x 10(6) CD34+ cells/kg per apheresis was collected after the second mobilization, compared with 0.16 with initial harvests (p = 0.0001). Forty-eight percent achieved a target CD34+ cell dose > or = 2.5 x 10(6)/kg when harvests from the first and second mobilizations were combined. Fifteen of 17 patients (88%) with > or = 1.5 x 10(6) CD34+ cells/kg harvested after first mobilization had > or = 2.5 x 10(6) CD34+ cells/kg collected when first and second harvests were combined, as compared with 42 of 102 (41%) achieving < 1.5 x 10(6) CD34+ cells/kg with first PBSC harvests (p = 0.0001). Second mobilizations with chemotherapy and G-CSF or G-CSF alone resulted in similar CD34+ cell yields. Toxicities of second mobilizations were comparable with those of first mobilizations. Seventy-nine patients (66%) received high-dose chemotherapy with PBSC support, with recovery of neutrophils and platelets in a median of 11 and 15 days, respectively. Transplant-related mortality was 4%, and event-free survival at 2 years was 0.34. It was concluded that second mobilization attempts in patients who fail to achieve > or = 2.5 x 10(6) CD34+ cells/kg on initial mobilization were successful in 48% of patients. G-CSF alone was as effective as chemotherapy plus G-CSF in mobilizing CD34+ cells and was associated with less morbidity.

Cardiac complications of intensive dose mitoxantrone and cyclophosphamide with autologous bone marrow transplantation in metastatic breast cancer.

Fifteen women with metastatic breast cancer undergoing autologous bone marrow transplantation were treated with an intensive induction regimen including cyclophosphamide and mitoxantrone in a phase I-II study. The cardiotoxicity of these two drugs in combination have not been previously reported. Three patients developed deeply inverted T-waves during or shortly following conclusion of high-dose chemotherapy with associated declines in ejection fraction of 0.04, 0.19 and 0.27. One patient developed a brief episode of congestive heart failure which resolved with supportive care. These three patients were the only ones to have received previous left chest wall radiotherapy during the course of their disease, prior to treatment with autologous bone marrow rescue. No patient developed dysrhythmia or QRS changes during a mean hospital stay of 33.7 days (range 27-40 days).

Sickle cell E hemoglobinopathy and pregnancy.

The incidence of E hemoglobinopathies has been increasing in the United States. This is the first known case report of hemoglobin S/E in pregnancy. Management was based on the similarities of the S/E and S/beta-thalassemia hemoglobinopathies, and included partial exchange transfusion. Complications included fetal distress, congenital hydrocephalus, and cleft lip and palate. It appears that S/E and E/beta-thalassemia hemoglobinopathies may entail increased perinatal risks, but that favorable pregnancy outcomes may be anticipated with homozygous hemoglobin E or hemoglobin E trait.

Recurrent "syncytial variant" of Hodgkin's disease: an immunohistologic diagnosis.

A case of recurrent Hodgkin's disease of the "sarcomatoid" or "syncytial variant" type was seen that occurred as an extension from the mediastinum to a previously uninvolved extranodal site (breast) and pericardium after treatment of classical nodular sclerosing Hodgkin's disease based in the lymph nodes. This histologic variant was composed of sheets of large, undifferentiated neoplastic cells with few, if any, diagnostic features of nodular sclerosing Hodgkin's disease. For this reason, the differential diagnosis of this variant was difficult and included non-Hodgkin's lymphoma (peripheral T-cell lymphoma), Ki-1-positive lymphoma, medullary carcinoma, metastatic carcinoma, melanoma, and granulocytic sarcoma. Immunologic analysis by immunoperoxidase technique showed a phenotype consistent with "syncytial variant" Hodgkin's disease: Leu-M1+, Ki-1+, IL-2+, HLA-DR+, T11-, pan B-, K-, lambda-, cytokeratin-, S-100-, muramidase-.

A collaborative, double-blind randomized study of cetiedil citrate in sickle cell crisis.

We have recently completed a double-blind, placebo-controlled, noncrossover study, the goal of which was to determine whether cetiedil citrate (cetiedil) could affect the course of vaso-occlusive crises in sickle cell disease. Patients, who presented to the emergency room at least 4 but no more than 24 hours after the onset of a painful vasoocclusive crisis severe enough to require hospitalization, were considered candidates for the study. Each patient received either placebo or cetiedil at one of the following three dosages: 0.2, 0.3, or 0.4 mg/kg body weight. The assigned drug dosage was given as a 30 minute intravenous infusion every 8 hours for 4 consecutive days. A total of 67 patients was enrolled in the study. Cetiedil, at its highest dosage (0.4 mg/kg body weight), was found to be significantly superior to placebo both in reducing the number of painful sites present on all 4 treatment days and in shortening the total time in crisis. No serious adverse reactions were observed during the course of the study. We conclude that cetiedil, given at a dosage of 0.4 mg/kg body weight, is therapeutically advantageous for sickle cell crisis.

Acute basophilic leukemia.

Acute basophilic leukemia was diagnosed in a 61-year-old black woman on the basis of 85 to 90 percent basophils in the peripheral blood as well as bone marrow and very high serum histamine level (more than 10,000 ng/ml). These complications occurred as a transformation from essential thrombocythemia. Accompanying this transformation, there was also cytogenetic change from 46XX karyotype to 46XX 2p+ in 66 to 90 percent of cells in the bone marrow. This may be the first reported occurrence of transformation of essential thrombocythemia into acute basophilic leukemia.

Sickle cell anemia and epidural extramedullary hematopoiesis.

Acute flaccid paralysis due to epidural extramedullary hematopoiesis developed in a 43-year-old man with sickle cell anemia. The patient showed no response to emergency decompressive laminectomy, radiotherapy, or exchange transfusion, and his neurologic deficit persisted unimproved. This is the first reported case of acute or irreversible spinal cord compression due to epidural extramedullary hematopoiesis in a patient with sickle cell anemia.

Correlation of hypercupremia with other acute phase reactants in malignant lymphoma.

Levels of copper, haptoglobin, fibrinogen and Factor VIII were measured in 30 patients with non-Hodgkin's lymphoma on 90 occasions in an attempt to demonstrate a possible correlation between hypercupremia and other acute phase reactants. The four parameters were measured simultaneously in active disease and in remission. The serum copper, along with other parameters, was significantly elevated in the active disease (P less than 0.001) and there was a high correlation between the levels of serum copper, fibrinogen and haptoglobin (P less than 0.001).