Multiple myeloma and hairy cell leukemia: a rare association or coincidence?

Hairy cell leukemia (HCL) and multiple myeloma (MM) are well-defined entities with distinctive clinical and pathological features. Although most cases of HCL and MM fit their classic descriptions, more recent studies have revealed that their clinical and morphological boundaries may not only overlap but a transformation of HCL into MM could also occur. We report another case of HCL followed by the development of MM after 9 years. He also developed hemarthrosis of his right ankle at the time of diagnosis of MM. PCR analysis of DNA extracted from the bone marrow aspirate was negative for the presence of a monoclonally rearranged immunoglobulin heavy chain gene. Immunophenoytping revealed no evidence of HCL. There are several possible explanations for the development of MM in HCL patients, such as the coexistence of separate disease entities or different clinical and morphologic phases of a single disease entity. An accurate diagnosis of HCL or MM is critical because of differences in their treatment. Hemarthrosis in this patient may also have been the first manifestation of MM, a feature of MM which has rarely been reported.

Sequential chemotherapy and radiotherapy for organ preservation in advanced resectable nonlaryngeal head and neck cancer.

Although there is no definite survival advantage to the use of sequential induction chemotherapy (CT) followed by radiotherapy (RT) in advanced resectable laryngeal cancer, this approach does succeed in preserving the larynx in many of these patients. The authors performed this study to analyze their results using a similar approach for patients with advanced resectable cancer located outside the larynx who would have required a total laryngectomy for oncologic or functional reasons. A retrospective study was performed at a single institution that included all patients with advanced resectable nonlaryngeal head and neck cancer treated with induction CT between January 1990 and August 1995. A total of 19 patients were included, with primary cancers located in the oropharynx in 14 patients, the hypopharynx in four, and the oral cavity and oropharynx in one. Eight patients had clinical stage III disease, and 11 patients had stage IV disease. Our treatment protocol consisted of two cycles of induction CT with cisplatin and 5-fluorouracil, followed by a third cycle of CT and subsequent RT in patients who achieved at least a clinical partial response (PR) after two courses of induction CT. Eighteen of 19 patients were evaluable for response. Overall, 13 patients (72%) had a major response (PR or CR) to induction CT at the primary site, and eight patients (57%) had a major response to chemotherapy in the neck. With a mean follow-up of 53 months (range, 24-71 months), the disease-specific survival was 57% for those patients with cancer of the oropharynx and oral cavity. In the subset of patients with hypopharynx cancer, 3 of 4 patients died of cancer despite achieving major response to induction CT. Organ preservation using sequential CT and RT for advanced resectable nonlaryngeal head and neck cancer is feasible, and the results in our experience with cancer of the oropharynx were similar to those reported for primary laryngeal cancer. Our limited experience using this protocol for cancer of the hypopharynx has been disappointing.

Phase II trial of trimetrexate for patients with advanced gastric carcinoma: an Eastern Cooperative Oncology Group study (E1287).

BACKGROUND: A Phase II study was conducted to evaluate the response, duration of response, and duration of survival of patients with measurable gastric carcinoma treated with trimetrexate (TMTX) who had not had prior chemotherapy. METHODS: Thirty-three patients with unresectable or metastatic gastric adenocarcinoma who had not received previous chemotherapy were treated with intravenous TMTX 12 mg/m(2) daily for 5 days. The dosage of TMTX was reduced to 8 mg/m(2) daily for 5 days for those who had received prior radiotherapy. The cycle was repeated every 3 weeks until disease progression or unacceptable toxicity occurred. RESULTS: Thirty-three patients could be analyzed with follow-up data. There was one Grade 5 (lethal) toxicity and four Grade 4 toxicities. Hematologic toxicity was the most common. The overall response rate was 21%, the overall median progression free survival was 2.7 months, and the overall median survival was 5.9 months for the entire cohort. No patients were alive at last follow-up. CONCLUSIONS: Though TMTX as a single agent has activity in gastric carcinoma with manageable toxicity, it cannot be recommended for routine use as a single agent due to the brief duration of response and median survival.

HIV-associated autoimmune hemolytic anemia complicated by pulmonary embolism following a red blood cell transfusion: case report and review of the literature.

BACKGROUND: Though positive direct antiglobulin tests are common in AIDS patients, overt hemolysis is rare. A hypercoagulable state has recently been recognized in these patients and may contribute to the thromboembotic complications previously reported in three patients with HIV-associated autoimmune hemolytic anemia. CASE REPORT: An AIDS patient with severe warm autoimmune hemolytic anemia developed a pulmonary embolus after a single red blood cell transfusion. CONCLUSION: There may be an increased risk of thromboembolism in AIDS patients with autoimmune hemolytic anemia who receive red blood cell transfusions, a concern we have previously raised. Prophylactic anticoagulation should be considered in this setting.

Hyposplenism from Mycobacterium avium complex infection in a patient with AIDS and immune thrombocytopenia.

We describe a patient with HIV-related immune thrombocytopenic purpura with known Mycobacterium avium complex (MAC) infection presenting with intracerebral hemorrhage associated with severe thrombocytopenia who failed splenectomy following unsuccessful trials of corticosteroids and intravenous immunoglobulin. His presplenectomy peripheral blood smear showed Howell-Jolly bodies and microscopic examination of his spleen demonstrated multiple granulomas with numerous acid-fast organisms replacing the normal splenic tissue. We postulate that splenic hypofunction secondary to overwhelming MAC infection contributed to the failure of the thrombocytopenia to promptly respond to splenectomy.

Abdominal presentation of Burkitt's lymphoma in an HIV-positive patient.

The incidence of non-Hodgkin's lymphoma (NHL) has greatly increased in the AIDS population. It has been estimated that 8% to 27% of newly diagnosed cases of NHL are related to AIDS. The vast majority are clinically aggressive B cell-derived lymphomas. AIDS-associated NHLs are classified according to their anatomic site of location into three classes: (1) systemic (both nodal as well as extranodal), (2) primary central nervous system, and (3) body cavity-based lymphomas. We present a case report of a patient with HIV infection who presented with abdominal pain and distension and was found to have an intraabdominal type of Burkitt's lymphoma. This case underlines the following points: 1. In the evaluation of acute abdominal disease in a patient with AIDS, both AIDS-related infections as well as malignancies should be sought in the differential diagnosis. 2. Computed tomographic scanning of the abdomen is the modality of choice for characterization of disease as well as direction of appropriate therapy. 3. AIDS-related NHL remains an important biologic model for investigating the development and progression of lymphomas in the immune-deficient host. 4. With the improved survival of patients with AIDS secondary to better prevention and treatment of infections, there may be an increase in AIDS-associated malignancies; therefore, further research pertaining to the development and characterization of therapy modalities of such malignant tumors is mandatory.

Aortic wall sarcoma with tumor emboli and peripheral ischemia: case report with review of literature.

Primary malignant tumors of the aorta are rare, only a handful of isolated cases having been described in the literature. Preoperative diagnosis of these tumors is more the exception than the rule. Diagnosis of aortic tumors is difficult as they can mimic many diverse conditions including atherosclerosis. We report a patient who presented with lower extremity claudication, renal infarction, and diffuse atherosclerosis and who was found to have tumor fragments in blood clots but no evidence of a primary tumor. Immunohistochemistry narrowed the differential diagnosis to a type of sarcoma. Six months later, he developed right flank pain due to a malignant fibrous histiocytoma that involved the abdominal aorta and that had initially manifested as tumor emboli.

Treatment of advanced pancreatic adenocarcinoma with 5-FU, leucovorin, interferon-alpha-2b, and cisplatin.

Previous laboratory and clinical studies support the ability of interferon (IFN) to enhance the antitumor properties of chemotherapy agents, including cisplatin and 5-fluorouracil (5-FU). A phase I-II clinical trial was initiated to treat several tumor types with IFN-alpha-2b, cisplatin, 5-FU, and leucovorin (LV), given daily for 5 days of a 28-day cycle. Because of preliminary results, this was continued as a phase II trial in 18 patients with metastatic adenocarcinoma of the pancreas. Each treatment day consisted of IFN 5 million u/m2 s.c. (maximum, 10 million U), CDDP 20 mg/m2 i.v. over 1 h, LV 20 mg/m2 i.v.p., and 5-FU 250-275 mg/m2 i.v.p. All patients had measurable disease with no prior chemotherapy for metastatic disease, and all had an Eastern Cooperative Oncology Group (ECOG) performance status of 1. Six of the 16 patients evaluable for response had partial responses (PRs) (37.5%) with a median response duration of 4 months, and all responding patients survived > or = 8 months. Median survival of all 18 treated patients was 5 months. Severe gastrointestinal toxicity (nausea, diarrhea, or requirement for i.v. hydration) was common. Grade 4 hematologic toxicity was seen in six patients. The response rate observed is promising and supports the concept that IFN may potentiate the effects of standard chemotherapy agents. However, the toxicities observed with this dosage schedule were considerable and further studies are needed to develop a less toxic regimen.

Polycythemia rubra vera.

PV represents a clonal disorder characterized by excessive erythropoiesis accompanied by low serum EPO levels. Two populations of erythroid progenitors have been identified in the BM of patients with PV. One population responds normally to EPO and the other, the malignant clone, is exquisitely sensitive to EPO. The latter phenomenon is regarded as the most readily accepted explanation for the pathophysiology of this disease, although other mechanisms have been proposed. Thrombohemorrhagiccomplications, which usually correlate with the hematocrit level, are the most important because of their frequency and severity. Preventing such complications represents one of the most important therapeutic goals. Diagnostic criteria have been established enabling an accurate diagnosis of PV, in which the majority of patients live an excess of 10 years. Some will develop a falling hematocrit secondary to PPMM, also termed the spent phase. Patients may also develop acute leukemia, which is increased in incidence if myelosuppressive therapy is used, compared with phlebotomies alone. The initial treatment is phlebotomy to an hematocrit of 45% or less. The studies of the PVSG have shown that chlorambucil produces excessive mortality from malignancy, and 32P and phlebotomy are associated with superior survivals which are equivalent. Because of the substantial risk of thrombotic complications, elderly patients, ie, those older than 70 years, should be treated initially with phlebotomy and myelosuppressive therapy, usually 32P. Hydroxyurea appears less leukemogenic than 32P or alkylating agents; however, recent reports have questioned this. IFN is a promising new agent which may become a standard form of therapy in the future.

Recurrent venous thrombosis as the presenting manifestation of acute lymphocytic leukemia: leukemic cell procoagulant activity is not responsible for the hypercoagulable state.

The association of cancer with clinical abnormalities of blood coagulation, including superficial thrombophlebitis, deep vein thrombosis (DVT), and disseminated intravascular coagulation (DIC) is well-known, particularly in patients with solid tumors and acute promyelocytic leukemia (APL). Less commonly appreciated is the potential for the development of venous thromboembolic disease (TED) in patients with acute lymphocytic leukemia (ALL). Multiple mechanisms have been implicated for the activation of coagulation in these patients, with an emphasis on the contribution made by the procoagulant properties of the tumor cells themselves. We present two cases of patients with pre-B cell ALL, both of whom developed recurrent TED as the presenting manifestation of their leukemia and/or heralding relapse. The blast cells from one of the patients were studied for the presence of procoagulant activity (PCA) and by Northern blot analysis for tissue factor (TF) messenger RNA (mRNA). Neither PCA nor TF mRNA could be identified in highly purified populations of the lymphoblast cells. We conclude that recurrent TED can be a manifestation of ALL and that mechanisms other than the release of tumor cell procoagulants should be sought to explain the pathogenesis of thrombosis in some patients.

The role of flow cytometry in the diagnosis of lymphoma: a critical analysis.

Flow cytometry, now used routinely to aid in the classification of leukemias, is increasingly being evaluated as a rapid technique for determination of surface antigens on the cells teased from lymph nodes and other masses with suspected lymphoma. The present study reviews biopsy specimens from patients examined during a two year period which were sent for flow cytometry with a diagnosis of suspected lymphoma. Sixteen of 25 samples (64 percent) produced cell suspensions of sufficient quantity and quality to be diagnostically helpful. Results showed that in 9/16 (56 percent) the diagnosis of lymphoma or cancer could be suspected by flow cytometry alone, while 4/16 were consistent with the final tissue diagnosis of normal or reactive hyperplasia. Three samples that came from patients who had morphologic evidence of malignant disease on biopsy (two Hodgkin's disease and one large cell lymphoma) had flow cytometry results that were interpreted as normal. Flow cytometry is rapid and appears to be virtually diagnostic of non-Hodgkin's lymphoma when a majority of cells are B cells with an abnormal kappa/lambda ratio (> 4.0 or < 0.25). Nonhematologic malignancy can be suspected if less than 75 percent of the cells show CD45 (common leukocyte antigen). Hodgkin's disease cannot be detected by flow cytometry as it is currently used, and as many as 15 percent (1/6 in this study) of lymphomas may show normal results. It is extremely helpful when the biopsy sample actually contains the cells of interest in large proportion. Loss of architectural relationships in the course of processing specimens for flow cytometry is a major disadvantage when small foci of lymphoma or tumor cells exist together with large amounts of stroma or normal lymphocytes.

Empirical chemotherapy for adenocarcinoma of unknown primary tumor site.

It is evident that no chemotherapy regimen can be considered standard for patients with ACUP. If after careful evaluation, a patient does not belong to a subset of patients with a higher chance of response, then the low likelihood of response to systemic therapy and the potential for treatment-associated toxicities must be reviewed with the patient. Should a trial of chemotherapy be chosen, this must be attempted with close monitoring for toxicity and should be discontinued unless a clear response is observed after a set time period, eg, two cycles of therapy. An effort should be made to ascertain whether there is a clinical protocol available at a regional center for which the patient would be eligible. For patients treated in a noninvestigational setting, we suggest a regimen such as FAM because of its relative tolerability and ease of administration. The most promising avenue for further study, and hopefully for future clinical practice, is the more precise identification of factors associated with a clearly defined response rate (either higher or lower) than patients with ACUP in general. The utilization of newer pathological or in vitro techniques for the study of these tumors should be encouraged as part of clinical trials because they may increase the number of patients who belong to specific subsets of ACUP associated with well-characterized responses to appropriate chemotherapy.

Treatment of myelodysplastic syndromes with daily oral idarubicin. A phase I-II study.

BACKGROUND: Idarubicin, a new anthracycline analogue, is available in an oral preparation, and responses have been observed using relatively aggressive therapy in patients with myelodysplastic syndromes (MDS). The authors studied whether a chronic low-dose schedule would be effective but less myelotoxic. METHODS: Forty-two patients with MDS received daily low-dose oral idarubicin in 5-week courses that included 3 weeks of treatment, followed by a 2-week rest period. Doses were escalated when possible after the second course, and each patient was to receive six courses. RESULTS: Only one partial response was observed. Although no patient had fatal bone marrow toxicity, only eight patients received the full six courses, primarily because of myelosuppression. CONCLUSIONS: This schedule of oral idarubicin is relatively safe but produces fewer responses than are reported with the high-dose pulse regimens.

The Clinical Oncology Career Development Award of the American Cancer Society. A 5-year evaluation.

BACKGROUND: In 1985, the American Cancer Society (ACS) replaced their Junior Faculty Clinical Oncology Program with the 3-year Clinical Oncology Career Development Award (COCDA). It was proposed that the longer duration and larger stipend of the COCDA would have a greater impact in encouraging promising young clinical oncologists to enter and remain in academic oncology. The COCDA was evaluated at this time to determine whether these goals had been achieved. METHODS: A questionnaire was sent to 104 of the total of 121 people who received awards in 1985, 1986, and 1987. RESULTS: A review of the 85 completed questionnaires showed that the COCDA had a significant impact on the recipients. Most have remained in academic settings and have flourished, as evidenced by their publication record and success in obtaining extramural funds, despite their clinical orientation. CONCLUSIONS: The COCDA has achieved its initial goals and will remain an important part of the professional education efforts of the ACS.

Immunological techniques to differentiate lymphoma from other malignancies.

Seven patients, who had lymph nodes or masses examined by both immunoperoxidase staining and flow cytometry, are presented to illustrate the value of each technique including a critical analysis of the current application of these techniques in the pathology laboratory. All seven patients had diagnoses established by immunoperoxidase staining using antibodies directed against: Leukocyte Common Antigen (LCA), Epithelial Membrane Antigen (EMA), Neuron Specific Enolase (NSE), Leu M1, B4 or chromagrafin and synaptosin. Flow cytometry, which could be more rapidly performed, when sufficient cells could be separated from the node or mass, was diagnostic in two of the seven cases. Flow cytometry failed to show abnormalities in Hodgkin's disease or solid tumors, but it was useful in rapid diagnosis of lymphoma, provided that the sample contained mostly involved tissue. Nodes in which there was a minor infiltration with lymphoma cells could only be detected by immunoperoxidase technique.