High-dose cyclophosphamide, etoposide and carboplatin with autologous bone marrow support for metastatic breast cancer: long-term results.

We report long-term results of high-dose cyclophosphamide, etoposide and carboplatin with ABMT in 20 patients with metastatic breast cancer. Median age of the group was 41 years, ECOG performance status = 0 in 18 patients and 1 in two patients. Twelve patients had received adjuvant chemotherapy. Predominant sites of metastases were lung (eight), chest wall (four), liver (four), bone (three) and lymph nodes (three). Response to pretransplant chemotherapy was complete (CR) in four patients, partial (PR) in 10 patients and stable (SD) in five patients. After high-dose chemotherapy eight patients were in CR, six PR, four SD and one progressive disease. Two patients died of regimen-related toxicities (candidal sepsis and alveolar hemorrhage). With a median follow-up period of 55 months (minimum 48 months), 12 patients have died of recurrent breast cancer, one died of toxicity of salvage chemotherapy, two are alive with disease, two are alive and free of progressive disease. One patient with relapsed disease was lost to follow-up. Median event-free survival is 6 months and median overall survival is 17 months. All three of the long-term disease-free survivors had predominantly nodal disease. Two of these three patients presented with metastatic disease and received high-dose chemotherapy with ABMT as part of initial therapy for breast cancer; two of three attained CR to standard-dose cytoreductive therapy; none received doxorubicin-containing adjuvant chemotherapy.

Gilbert's syndrome co-existing with and masking hereditary spherocytosis.

An unusual case of co-existing Gilbert's syndrome and hereditary spherocytosis is reported. Diagnostic strategies are presented, and the literature is reviewed for simultaneous presence of these disorders.

Idarubicin-induced pigmentary changes of the nails.

A case of acute myelocytic leukemia of the FAB-M2 subtype in a patient who experienced pigmentary nail changes in conjunction with idarubicin therapy is presented. Although doxorubicin and daunorubicin have been reported to cause nail pigmentation changes, this is the first case report to describe these changes with idarubicin.

Paclitaxel-induced radiation recall dermatitis.

The authors present a case of radiation recall dermatitis occurring in a patient receiving paclitaxel shortly after completion of radiation therapy. A brief review of previously reported taxane-induced radiation recall reactions is provided.

Azathioprine as a steroid-sparing agent in radiation pneumonitis.

Radiation therapy is commonly used for treatment of neoplastic disease involving the thorax. Treatment complications include radiation pneumonitis that may require therapy with corticosteroids which possess significant side effects. We report the use of azathioprine as a steroid-sparing agent in a patient with severe radiation pneumonitis and steroid-induced myopathy.

Acute myeloid leukemia evolving from essential thrombocythemia in two patients treated with hydroxyurea.

Essential thrombocythemia (ET) is an uncommon myeloproliferative disorder, which is thought to develop from a multipotent stem cell. Like other myeloproliferative diseases, ET is associated with an increased risk of development of acute leukemia (AL). However, the large majority of cases of leukemic transformation in ET are thought to be related to prior therapy, usually radioactive phosphorous or alkylating chemotherapy, and the development of AL in ET is extremely rare in the untreated patient. In this report, two cases of ET which evolved into AL without prior exposure to radiation or alkylating agents, and which were treated with long-term hydroxyurea therapy, are described. The first case had cytogenetic changes in the bone marrow suggestive of therapy-associated leukemia, and the second developed myelodysplastic syndrome on therapy which was likely chemotherapy-induced and led to acute leukemia. Prolonged used of hydroxyurea in patients with ET may lead to therapy-associated acute leukemia.

Angiofollicular lymph node hyperplasia (Castleman's disease).

This review provides a comprehensive assessment of angiofollicular lymph node hyperplasia (ALNH) or Castleman's disease including pathogenesis, clinical presentation, histomorphologic and immunophenotypic findings, laboratory results, treatment, and prognosis. A division of ALNH into clinically relevant subtypes provides a framework for the consideration of the disorder. A comprehensive search of the medical literature involving ALNH using Medline was performed. Reports judged to be significant for the understanding of the disorder were analyzed and their findings incorporated into this review. ALNH is divided into localized/unicentric ALNH and generalized/multicentric ALNH due to the profound clinical differences seen between these variants. Localized/unicentric ALNH is separated by clinical and histomorphologic criteria into hyaline-vascular (HV) and plasma-cell (PC) subtypes. Generalized/multicentric ALNH may be divided by clinical criteria into generalized/multicentric ALNH without neuropathy (non-neuropathic) and generalized/multicentric ALNH with neuropathy (POEMS-associated or neuropathic). The dichotomy between these two subtypes is not absolute, with considerable clinical overlap occurring among patients presenting with generalized disease. Immunophenotypic and molecular probe studies demonstrate clonal B-cell lymphocyte populations in some cases, particularly those with generalized/multicentric ALNH. However, the finding of clonal populations is of no value in predicting malignant clinical progression. We conclude that using this division of ALNH, patients presenting with symptoms and histomorphology consistent with ALNH can be subdivided into the appropriate category of ALNH. Localized or unicentric disease, either HV or PC subtype, has an excellent prognosis with surgery being curative in the majority of cases. Generalized or multicentric disease indicates a poor prognosis with short survival, with the neuropathic variant possessing resistance to steroids and chemotherapy and a corresponding worse prognosis.

Bilateral synchronous testicular germ cell cancer.

Bilateral synchronous testicular cancer is a rare occurrence usually associated with similar histologic findings in each testicle. We describe eight patients with bilateral synchronous testicular germ cell cancer, of whom four had dissimilar histologic findings. Contralateral disease in three patients was identified only by testicular ultrasonography or intraoperative exploration of the contralateral testicle, and in two cases by palpation 6 months after identification of the primary cancer. Treatment was determined by conventional staging and five of eight patients have remained free of recurrent disease.

Lymphomatoid papulosis associated with Ki-1-positive anaplastic large cell lymphoma. A report of two cases and a review of the literature.

BACKGROUND: Lymphomatoid papulosis (LyP) is an uncommon disorder characterized by recurrent papulonodular cutaneous lesions that last from 4 to 5 weeks and often heal with hypopigmented or hyperpigmented scarring. Prognosis is varied, 10%-20% of patients have associated lymphomas: mycosis fungoides, T-cell immunoblastic lymphoma, or Hodgkin's disease, which can precede, occur simultaneously with, or follow the diagnosis of LyP. Anaplastic large cell lymphoma (ALCL) is histologically and phenotypically similar to LyP and also appears as part of this disease spectrum. Recent reports analyzing immunophenotype and T-cell receptor gene rearrangements in patients with both LyP and lymphoma suggest that they are derived from an identical T-cell clone, in the rare cases studied. METHODS: The case histories of two patients with LyP in whom ALCL involving the skin and lymph nodes subsequently developed are presented. RESULTS: Intensive treatment with combination chemotherapy resulted in complete remission of ALCL in both patients, followed by the recurrence of LyP. A spontaneous remission of LyP occurred in the initial patient described, whereas the second patient suffered recurrences of both LyP and ALCL despite therapy. CONCLUSIONS: The case histories presented illustrate the immunophenotypic and morphologic similarities of ALCL and LyP, and the difficulties in distinguishing between them. Both entities can occur in a single patient, as shown by this report, supporting a close relationship between these processes. However, different clinical behavior and response to therapy are apparent, which connote a fundamental difference in the biologies of these neoplastic disorders. A review of the literature concerning the association between these entities is provided.

Inhibitory effects of lysine analogues on t-PA induced whole blood clot lysis.

The lysine analogues epsilon-aminocaproic acid (EACA) and trans-4-amino-methyl cyclohexane carboxylic acid (AMCA) are used to prevent excessive bleeding in patients with coagulopathies, such as hemophilia and thrombocytopenia, or in those who have received tissue plasminogen activator (t-PA). However, their relative efficacy in inhibiting lysis of clots that have been formed in the presence of exogenous t-PA or that have been formed and then exposed to exogenous t-PA has not been well characterized. The present study utilized blood from normal volunteers and 125I-fibrinogen in a dilute whole blood clot assay to determine the relative concentrations of lysine analogues required for inhibition of clot lysis induced by exogenous t-PA. AMCA (0.06 mM) and EACA (0.6 mM) were effective in prolonging clot lysis if (1) whole blood clots were formed and then exposed to a lysine analogue and exogenous t-PA or if (2) whole blood clots were formed in the presence of exogenous t-PA and a lysine analogue. However, their inhibitory effect was markedly reduced if clots were formed in the presence of t-PA and then exposed to either of the lysine analogues. The analogues did not inhibit the initial binding of t-PA to fibrin. They did inhibit binding of plasminogen to fibrin as well as the activation of plasminogen by t-PA in the absence of fibrin. The data suggest that lysine analogues, even at low concentrations, reduce the rate of t-PA induced whole blood clot lysis by several mechanisms.

Erythropoietin in the treatment of iron overload in a patient with hemolytic anemia and pyruvate kinase deficiency.

Iron overload has been reported with pyruvate kinase deficiency. Erythropoietin (EPO) may lead to iron deficiency; thus, patients who are unable to be phlebotomized due to anemia may benefit from EPO as a treatment of iron overload.

Arsenic intoxication presenting with macrocytosis and peripheral neuropathy, without anemia.

A case of arsenic intoxication associated with macrocytosis and neuropathy, without anemia, is presented. Evaluation of a 68-year-old man with a long history of peripheral neuropathy and persistent macrocytosis revealed exposure to an insecticide. Analysis of urine and hair revealed elevated levels of arsenic. A short course of d-penicillamine failed to promote urinary excretion of arsenic. Removal of the insecticide resulted in resolution of macrocytosis and slight improvement of neuropathy. This case emphasizes that arsenic intoxication should be considered in patients with macrocytosis with peripheral neuropathy, even in the absence of anemia.

Multicentric angiofollicular lymph node hyperplasia and associated carcinoma.

There is a well described association between multicentric angiofollicular hyperplasia and non-Hodgkin's lymphoma and/or Kaposi's sarcoma. Two cases of multifocal angiofollicular hyperplasia and associated carcinomas and non-Hodgkin's lymphoma are reported. We suggest that underlying immunological defects in patients with multicentric angiofollicular hyperplasia make them susceptible to the development of carcinomas, as well as non-Hodgkin's lymphoma and Kaposi's sarcoma.

Mean platelet volume improves upon the megathrombocyte index but cannot replace the blood film examination in the evaluation of thrombocytopenia.

The measurement of the number of platelets larger than 3 microns (megathrombocyte index) is the first element in the evaluation of thrombocytopenia. This is currently performed by counting the number of large platelets on the peripheral blood film. The MPV (mean platelet volume) is an automated measurement of the platelet volume. This study examines the mean values, correlations, sensitivity, specificity and the receiver operating characteristic curve (comparison of two tests) to determine which of these tests better separates the production state. For increased vs. decreased production, the MPV was 10.0 + 1.9 fL and 8.0 + 1.5 fL (P < .0001) respectively and the megathrombocyte index (MEGA) was 19.0 + 17.6% and 11.5 + 14.9% (P < .007) respectively. The correlation with the state of production was better for MPV (R = .47) than for MEGA (R = .20). For the MPV a sensitivity of 80% occurred with the MPV > or = 8.4 fL with a specificity of 71%. For a MEGA > or = 6%, the sensitivity was 80% but the specificity was 43%. For any MPV the sensitivity and specificity were better than for any MEGA. The Receiver Operating Characteristic Curve demonstrated that the MPV is a better test than the MEGA for separating the production into increased and decreased states. The MPV is a better test than the MEGA and will add to, but not replace, examination of the peripheral blood film in the diagnosis of thrombocytopenia.

Diffuse alveolar hemorrhage following autologous bone marrow infusion.

Autologous BMT performed in a 57-year-old woman with relapsed large cell lymphoma was complicated by two consecutive episodes of diffuse alveolar hemorrhage (DAH). The second episode occurred immediately after infusion of autologous BM. DAH is an increasingly recognized complication of autologous BMT and carries a high mortality. It is characterized by dyspnea, cough, bilateral pulmonary infiltrates and progressively bloodier aliquots of bronchoalveolar lavage fluid. The pathogenesis is probably multifactorial involving an initial insult to lung endothelium with inflammatory cells serving as the mediators of subsequent injury. The rapid development of DAH following marrow infusion strongly implicates DMSO as a potential cause in our patient.

Pericarditis associated with acral erythema of chemotherapy: a syndrome of cutaneous and serosal toxicities?

A nineteen-year-old woman whose Hodgkin's disease had relapsed experienced acral erythema in association with a asymptomatic pericardial friction rub following autologous bone marrow transplantation. An echocardiogram revealed a large pericardial and right pleural effusion. Since blood cultures gave negative results, renal function was normal, and the patient had neither neutropenia nor elevated temperature, an infectious cause was deemed unlikely and invasive procedures were not performed. These effusions resolved spontaneously. We propose that this patient's acral erythema and associated pericardial and pleural inflammation represent cutaneous and serosal toxic reactions to high-dosage chemotherapy that occur with the onset of leukocyte recovery. If so, acral erythema may signal the beginning of a toxic drug reaction. The appearance of erythema associated with lymphocyte recovery is due to immune hypersensitivity secondary to immaturity of the reconstituting immune system. Thus, we recommend that patients with acral erythema be examined for pleuropericarditis, especially if they experience chest pain.

Nonbacterial thrombotic endocarditis clinically mimicking veno-occlusive disease of the liver complicating autologous bone marrow transplantation.

Nonbacterial thrombotic endocarditis is an uncommon, but well-described, complication of bone marrow transplantation. We describe a case of nonbacterial thrombotic endocarditis following autologous bone marrow transplantation that was marked by weight gain, hepatomegaly, ascites, and extreme hyperbilirubinemia leading to a clinical diagnosis of hepatic veno-occlusive disease. Autopsy revealed nonbacterial thrombotic endocarditis of the tricuspid and pulmonic valves, and passive congestion of the liver, but there was no evidence of veno-occlusive disease. We discuss the pathophysiology and clinical features of nonbacterial thrombotic endocarditis and review its occurrence in association with bone marrow transplantation. Nonbacterial thrombotic endocarditis is often difficult to detect clinically and should be a diagnostic consideration in patients who develop systemic emboli or congestive heart failure after bone marrow transplantation.