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Pneumocystis carinii pneumonia among patients without AIDS at a cancer hospital.

OBJECTIVES: To determine the predisposing factors, attack rate by underlying disease, and outcome of Pneumocystis carinii pneumonia among patients without the acquired immunodeficiency syndrome (AIDS) at a cancer center. DATA SOURCE: Twelve-year retrospective review from a tertiary-care cancer center. STUDY SELECTION: One hundred forty patients, constituting 142 cases, with morphologically proved P carinii pneumonia. DATA SYNTHESIS: Hematologic malignancy (47%) (including lymphoma [27%] and leukemia [18%]), solid tumor (31%), or bone marrow transplantation (18%) was the underlying condition in the majority of cases. Twenty-five cases (18%) were diagnosed at autopsy. All but seven patients had previously established predisposing factors for P carinii pneumonia, including corticosteroid use in 87%. The attack rate for hospitalized patients with primary or metastatic brain tumor increased during the 12-year interval. The attack rates for hospitalized patients with hematologic neoplasm or bone marrow transplantation were stable. The overall mortality rate did not change during the period reviewed. CONCLUSIONS: Despite the availability of effective prophylaxis, P carinii pneumonia continues to occur among patients with neoplastic disease. In addition to patients with certain hematologic neoplasms, those with primary or metastatic brain neoplasm who receive corticosteroids are at risk for the development of P carinii pneumonia and should receive P carinii pneumonia prophylaxis.

Acquired Immunodeficiency Syndrome↗

Acute myeloblastic leukemia associated with mediastinal nonseminomatous germ cell tumors. Report on two cases.

The demonstrated association with hematologic neoplasms may partially account for the poor survival of patients with mediastinal nonseminomatous germ cell tumors (MNSGCT) compared to patients with testicular and retroperitoneal counterparts. It has been shown that the median interval from the diagnosis of MNSGCT to the diagnosis of the hematologic disorders is 6 months, which contrasts sharply with the average time of 2 to 3 years for the development of therapy-related leukemias. The 2 cases herein described, 1 male and 1 female, developed acute M2 leukemia 4 and 2 years after the diagnosis of MNSGCT. In the second patient (the first female ever described), we cannot exclude a pathogenetic role of the PEB regimen (platinum, etoposide, bleomicin), even though the total dose of etoposide administered has been demonstrated to have a mild leukemogenic potential. This is not the case of the first patient, who did not receive adjuvant chemotherapy after the radical resection of primary MNGSCT and developed the hematologic disorder a few months after local recurrence. In conclusion, the time elapsed from chemotherapy administration does not discriminate the hematologic neoplasms associated to MNGSCT from those related to therapy.

Adolescent↗

Secondary myelodysplastic syndromes and acute leukemias.

Secondary myelodysplastic syndrome (sMDS) and secondary acute leukemia (sAL) are hematologic neoplasms occurring a few years following another primary malignancy, and are believed to be related to the chemotherapy used for the primary disease. Alkylating agents are considered to be more leukemogenic than other chemotherapeutic agents. Hodgkin's disease and multiple myeloma, among the hematologic neoplasms, and breast cancer among the solid tumors, are associated with this late complication more than other malignancies. The clinical picture is similar to primary MDS. However, the course is rapid, with early leukemic transformation and poor prognosis. since many sMDS patients are relatively young, it is reasonable to suggest an aggressive approach, i.e. bone-marrow transplantation (BMT) or antileukemic chemotherapy. The older patients may be offered low dose ara-c (LDAC), differentiating agents or clinical trials with growth factors. Even the responders survive no more than a few months.

Acute Disease↗

Hematopoietic malignancies and related disorders among benzene-exposed workers in China.

Although the relationship between benzene and acute nonlymphocytic leukemia (ANLL) is well established, most of the analytic cohort investigations examining the relationship between benzene and hematologic neoplasms have evaluated only death certificates to validate diagnoses. In a follow-up study of 74,828 benzene-exposed and 35,805 non-exposed workers in China, pathology reports, medical records, and/or histopathologic material were reviewed for all patients with hematopoietic malignancies to ensure correct classification and to provide clinicopathologic descriptions. Eighty-two patients with hematopoietic neoplasms and related disorders were identified among benzene-exposed workers, including 32 cases of acute leukemia, 7--myelodysplastic syndrome (MDS), 9--chronic granulocytic leukemia (CGL), 20--malignant lymphoma or related disorder (ML), 9--aplastic anemia, and 5 others. Among the comparison group, 13 hematologic malignancies were observed, including 6 patients with acute leukemia, 2--CGL, 3--ML, and 2 others. The hematopathologic characteristics of the benzene-exposed ANLL cases resembled those following chemotherapy or radiotherapy. ANLL in workers exposed to benzene may represent a distinct clinicopathologic entity, with characteristics similar to treatment-related ANLL, including a preceding preleukemic phase in some patients. Results in our series, one of the largest to data, also indicate that a greater diversity of hematologic neoplasms is evident among benzene-exposed workers than previously described.

Adult↗

Serum nm23-H1 protein as a prognostic factor in hematological malignancies.

A nondifferentiating mouse myeloid leukemia cell line produces differentiation-inhibiting factors. One of these factors was purified as a homologue of nm23. The nm23 gene was isolated as a metastasis-suppressor gene that exhibits low expression in high-level metastatic cancer cells. The nm23 gene was overexpressed in acute myelogenous leukemia (AML) cells and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML. Multivariate analysis of putative prognostic factors revealed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. The overexpression of nm23-H1 was also observed in various hematological neoplasms. To use nm23 overexpression to determine the prognosis for lymphoma, we established an enzyme-linked immunosorbent assay (ELISA) technique to determine the serum level of nm23-H1 protein. This assay is far simpler than that used to determine nm23 mRNA by reverse transcriptase-polymerase chain reaction (RT-PCR). Using this system, we measured nm23-H1 protein levels in many hematological malignancies. Serum nm23-HI levels were significantly higher in patients with all of the hematological neoplasms tested (AML, chronic myelogenous leukemia, acute lymphoblastic leukemia, (ALL) myelodysplastic syndrome (MDS) and malignant lymphomas) than in normal controls. An elevated serum nm23-H1 protein concentration predicted a poor outcome for AML and non-Hodgkin's lymphoma. Especially in diffuse large B-cell lymphoma (DLBCL), seram nm23-H1 protein levels were an important prognostic factor in planning an appropriate treatment strategy for DLBCL. The serum nm23-H I protein levels probably depend on the total mass of malignant cells overexpressing nm23-H1.

Antigens, Viral↗

Family cancer history and risk of childhood acute leukemia (France).

OBJECTIVE: A case-control study was carried out to investigate the role of a family history of solid tumor or hematologic neoplasm in the etiology of childhood acute leukemia. METHODS: Family cancer history in first- and second-degree relatives was compared in 279 incident cases (242 cases of acute lymphocytic leukemia and 37 of acute myeloid leukemia) and 285 controls. Recruitment was stratified by age, gender, hospital, area of residence, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. RESULTS: A significant association between childhood acute leukemia and a family history of hematologic neoplasm (OR = 2.7, confidence interval (CI) = 1.1-6.9) was found. This association was particularly clear-cut when the cases were restricted to acute myeloid leukemia (OR = 13.3, CI = 2.5-70.9). Childhood acute leukemia was associated with a family history of solid tumor (OR = 1.5, CI = 1.0-2.2), and elevated odds ratios were observed for family history of gastrointestinal cancer and melanoma. Those results are most unlikely to be explained by socioeconomic status and familial structure, which were very similar for the cases and controls. Differential misclassification is also unlikely for the first-degree relatives, even though it is difficult to rule it out for the second-degree relatives' history. CONCLUSION: The present study supports the hypothesis that a family history of cancer may be a risk factor for childhood acute leukemia.

Acute Disease↗

[2 cases of neutropenic enteropathy and bone marrow hypoplasia. An association not reported in Mexico].

Neutropenic enterocolitis (NE) is a serious complication in neutropenic patients; it often affects the cecum and the ascending colon. Most cases have been reported in neutropenic patients after chemotherapy for hematologic neoplasms, and some in association with conditions such as rheumatoid arthritis, benign cyclic neutropenia, and solid neoplasms. As far as we know, four cases of NE associated to AA (aplastic anemia, hypoplastic bone marrow) have been previously reported, two of them with autopsy studies. The macroscopic findings in the enterocolonic lesions were not illustrated. We report the first two cases in Mexico. The NE was neither clinically nor radiographically suspected initially, i.e. the morphologic diagnosis of their colonic lesions were amebic colitis in one and edematous ulcerated colitis in the other. Medical treatment without surgery was instituted. Both died. The macroscopic aspect of the enterocolonic lesions in NE associated to aplastic anemia in our two patients was similar to that in NE associated to hematologic neoplasms. In Mexico there is little experience in the clinical, radiographic or morphologic diagnosis of this rare association.

Adult↗

[Evaluation of carcinoembryonic antigen (CEA) in patients with neoplasms and hematologic diseases].

Carcinoembryonic antigen (CEA), a oncofetal glicoprotein, has been regarded as specific marker for colorectal cancer initially and restricted to the significance of tumor-associated antigen afterwards. Circulating CEA levels were determined in 47 patients with hematologic malignancies, resulting elevated in 10 (21%). The highest values had been discovered in a chronic lymphocitic leukemia complicated by primary hepatoma, causing the problem of the role played by the second tumor, likewise to another CEA-positive patient with the association "Hodgkin's disease-pancreatic carcinoma". The CEA employment had not been particularly satisfactory in the therapeutic monitoring and in the early detection of the relapses, in opposition to the results referred in the colorectal, mammary and bronchogenic carcinoma.

Carcinoembryonic Antigen↗

Multicentric reticulohistiocytosis and cancer: a case report and review of the literature.

Multicentric reticulohistiocytosis (MR) is a syndrome characterized by papulonodular skin lesions, a debilitating polyarthritis, and characteristic histologic findings. It is a rare disorder with only 82 cases reported. Twenty-eight percent had an associated neoplasm. Hematologic malignancies (four) and neoplasms arising from the breast (four), cervix (three), stomach (three), ovary (two), colon (two), lung (one), pleura (one), and from an unknown source (two) were all seen associated with MR. Eleven cases (including our own) were available for review. The papulonodular skin involvement was the initial manifestation (alone or concurrent with the polyarthritis) in 90% of our cases. The diagnosis of MR preceded that of the associated neoplasm in 73% of the cases. A case report is presented illustrating the relapse of MR before the clinical relapse of the associated tumor, and the response of both the tumor and MR to combination chemotherapy with cyclophosphamide, methotrexate, 5-fluorouracil, and prednisone when prednisone and aspirin alone failed to relieve the symptoms of MR. Steroids were not beneficial in the patients reviewed. The best management of MR associated with a neoplasm is the best management of the primary neoplasm. Cytotoxic chemotherapy including cyclophosphamide should be considered if there is progression of the MR in order to control the symptoms of MR and prevent a progressive debilitating arthritis.

Antineoplastic Combined Chemotherapy Protocols↗

Paraneoplastic vasculitis associated with esophageal carcinoma.

We report a case of esophageal carcinoma associated with paraneoplastic vasculitis. A 69-year-old man suffered from low-grade fever and numbness of the lower limbs for 3 months before esophageal and gastric carcinomas were detected. Concurrent infection or collagen disease was ruled out following clinical and laboratory examinations. In April 1996, the gastric carcinoma was completely removed by endoscopic mucosal resection, but the symptoms remained. Three weeks later esophagectomy was performed for esophageal carcinoma after which time the fever and numbness disappeared. The esophageal carcinoma was a well-differentiated squamous cell carcinoma invading into the submucosal layer. Twenty-two lymph node metastases were found in 68 resected lymph nodes. Latent thyroid cancer was found. Histologically, vasculitis was detected in the esophagus, stomach and serratus anterior muscle. The distribution and degree of vasculitis were most pronounced in the esophagus. The concurrent onset and spontaneous resolution of fever and numbness after the removal of the esophageal carcinoma suggested a paraneoplastic origin. The majority of patients with malignant neoplasm-associated vasculitis had hematologic neoplasms. Cases of esophageal carcinoma associated with paraneoplastic vasculitis are extremely rare.

Aged↗

Prospects for interleukin-2 therapy in hematologic malignant neoplasms.

Interleukin-2 (IL-2) is a regulator of diverse functions of the immune system that can induce regressions in some experimental and human tumors. These early findings suggest a potential role for IL-2 in the treatment of certain malignant neoplasms including lymphomas and leukemias. Advanced, rapidly growing tumors are generally not amenable to immunotherapy. Therefore, it is more likely that protocols with IL-2 will be used to prolong remission and prevent relapse in leukemia patients with minimal tumor load. Several approaches are currently being tested in animal experiments and clinical trials. Activation of tumor-reactive lymphocytes (specific or nonspecific) by IL-2 in vivo may eradicate residual leukemia in patients with occult disease. In vitro-propagated autologous or allogeneic leukemia-reactive T cells may be infused with IL-2 to facilitate the tumor destruction. The IL-2 enhances monoclonal antibody-dependent effector systems, such as antibody-dependent cell-mediated cytotoxicity in vivo. Monoclonal antibodies recognizing epitopes on leukemia/lymphoma cells could therefore be used with IL-2 to target nonspecific effectors to destroy tumor cells. Other cytokines appear to potentiate various antitumor activities of IL-2, including cytotoxicity of antigen-specific T lymphocytes or lymphokine-activated killer cells in vitro, and these combined effects may be exploited in clinical trials in which more than one cytokine is used simultaneously or in sequence. Finally, a stepwise completion of clinical protocols testing this immunologic approach in combination with other treatment modalities is necessary.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗

[Advance of research on survivin in hematological malignancies--review].

Survivin a novel member of the inhibitor of apoptosis protein family, is overexpressed in most types of cancer but not in normal differentiated adult tissues. Its mRNA expression levels among hematogical malignancies are characteristic in each type, subtype and distinctive in different phases of disease, making it a reliable diagnostic marker for clinical stages. Recently, researches indicate that high levels of survivin expression are associated with a poor prognosis and may be involved in tumor resistance to multiple chemotherapeutic drugs. In addition, experiments demonstrate that leukemic vaccination with DC pulsed with survivin antigen in vitro inhibit the proliferation of leukemic cells. Furthermore, when transferred survivin antisense oligodeoxynucleotide or dominant-negative mutant survivin into, malignant cells can be induced apoptosis mediated by downregulation in survivin expression. These findings suggest that survivin may serve as a potential target for biological strategies against hematological neoplasms. This review focuses on expression of survivin in hematological malignancies, effects of survivin on drug-resistance and prognosis of hematological malignancies, and application of survivin in the treatment of hematological malignancies.

Apoptosis↗

CD4+/CD56+ haematodermic neoplasm: a preculsor haematological neoplasm that frequently first presents in the skin.

CD4+/CD56+ hematodermic neoplasm, formerly known as blastic NK cell lymphoma, is an aggressive and rare preculsor hematologic neoplasm recently recognized by the WHO-EORTC classification consensus for cutaneous lymphomas. The neoplasm tends to affect elderly patients, who usually present with skin lesions but often have a disseminated disease, including bone marrow involvement. Although the lesions are composed of cells with a lymphoblast-like morphology and an NK-cell phenotype, exhibiting a CD4+, CD56+ positive immunophenotype, recent studies support a relationship to plasmacytoid dendritic cells. Because of the rarity of this disease, we describe two patients suffering a CD4+/CD56+ hematodermic neoplasm.

Aged↗

De novo internal neoplasms after liver transplantation: increased risk and aggressive behavior in recent years?

The goal of the study was to determine the incidence and variables associated with post-liver transplantation (LT) de novo internal neoplasms development, excluding skin tumors and hepatocellular carcinoma. Medical records were reviewed for recipient/donor demographics, viral serology, cause of liver disease, interval from LT to tumor diagnosis, predisposing factors, immunosuppression and survival. Forty-one neoplasms (31 solid and 10 hematologic) developed in 772 recipients (5.3%) transplanted between 1991 and 2001. Time to tumor diagnosis was longer in patients transplanted before 1995 than in those transplanted afterwards (58 vs. 22 months; p<0.05). Hematologic neoplasms (HN) appeared earlier than solid (2 vs. 21 months; p<0.001), were more prevalent in those transplanted after 1995 than before (32% vs. 12.5%), and had lower survival than solid (2 vs. 21 months, p<0.001). While HCV was the most frequent indication in HN (70%), alcohol was that of solid tumors (71%). Overall, risk factors for de novo neoplasms included alcohol and immunosuppression (p<0.01). In patients undergoing LT in recent years, there is a higher incidence of HN with de novo internal neoplasms developing at earlier time-points than in those transplanted years ago. Risk factors for tumor development include alcohol, HCV and possibly strong immunosuppression.

Adult↗

Treatment of acute promyelocytic leukemia and other hematologic malignancies with arsenic trioxide: review of clinical and basic studies.

Acute promyelocytic leukemia (APL) is now the most potentially curable subtype of acute myeloid leukemia in adults because of the introduction of novel approaches in the management of this disease. All-trans-retinoic acid (ATRA)-based therapy is now the first-choice treatment of patients presenting with de novo APL, and clinical studies have shown that nearly all patients who receive ATRA therapy achieve complete remission. However, approximately 20% to 30% of APL patients eventually have relapses with resistance to further ATRA treatment. Arsenic trioxide (As2O3 [ATO]) has been established as highly effective therapy for patients with APL, even for those with disease refractory to ATRA. Furthermore, results of recent studies have suggested a broad therapeutic potential for ATO in the treatment of hematologic malignancies beyond APL. In this review, we discuss the clinical activity and multiple mechanisms of ATO therapy in the management of APL and other hematologic neoplasms.

Antineoplastic Agents↗

Angiogenic growth factors: autocrine and paracrine regulation of survival in hematologic malignancies.

Recent research has focused on the role of angiogenic growth factors and their ability to mediate tumor growth and metastases, both in solid tumors and in hematologic malignancies. The bone marrow microenvironment is the setting for a wealth of complex interactions that include cell-to-cell contacts as well as secretion of and response to soluble factors. Abundant evidence supports the role of basic fibroblast growth factor (bFGF) in contributing to the dysregulation of apoptosis that is the hallmark of chronic lymphocytic leukemia (CLL). In fact, CLL cells themselves express bFGF; intracellular levels of this cytokine correlate with clinical CLL stage. Other stromal factors mediate the inhibition of apoptosis in CLL as well, suggesting that strategies to block the responses of CLL cells to these factors may represent effective therapies. More broadly, the class of agents known as angiogenesis inhibitors may offer important advantages with respect to the treatment of numerous types of malignancies. Currently, a number of clinical trials are under way to evaluate the clinical potential of several different angiogenesis inhibitors in several hematologic neoplasms.

Angiogenesis Inhibitors↗

Changing pattern of AIDS: a bone marrow study.

We compared bone marrow findings in 2 groups of patients with AIDS during 2 different periods: group 1, n = 20; male/female ratio, 19/1; and group 2, n = 120; male/female ratio, 6/1. Bone marrow iron stores were decreased significantly in group 2 (P < .01), and the incidence of AIDS-related lymphomas was higher, with frequent bone marrow involvement. Two group 1 patients had Kaposi sarcoma, and a 21-month-old girl with transfusion-transmitted AIDS had Burkitt-like lymphoma. In group 2, 44 patients had a history of malignant neoplasms, including Kaposi sarcoma (10 cases), hematologic neoplasms (33 cases), and metastatic leiomyosarcoma (1 case). Of the 120 patients, 15 (12.5%) had bone marrow involvement by malignant neoplasms. The majority of the non-Hodgkin lymphomas were high-grade lymphomas. Patients with AIDS-related malignant neoplasms had higher CD4+ cell counts and viral loads than patients without malignant neoplasms (P < .01, P < .05, respectively). The finding of decreased iron stores in patients with AIDS might aid clinical management of their anemia. The increased incidence of malignant neoplasms, especially lymphomas, in recent years might be related to prolonged survival but with incomplete reconstitution of immune function after antiretroviral therapy.

Acquired Immunodeficiency Syndrome↗

Angiogenesis in hematologic malignancies.

Angiogenesis is defined as the formation of new capillaries from preexisting blood vessels and plays an important role in the progression of solid tumors. Recently a similar relationship has been described in several hematologic malignancies. Expression of the angiogenic peptides vascular endothelial growth factor (VEGF) and basic fibroblast growth factor correlates with clinical characteristics in leukemia and non-Hodgkin's-lymphoma and the serum/plasma concentrations serve as predictors of poor prognosis. Increased bone marrow microvessels in multiple myeloma (MM) are correlated with decreased overall survival. Thalidomide which has antiangiogenic effects and direct cytotoxic effects was found to be effective in MM, myelodysplastic syndrome and acute myeloid leukemia (AML). Preliminary data indicate activity of VEGF-tyrosine kinase inhibitors in AML. Clinical research is now aimed at testing antiangiogenic treatment strategies in several hematologic neoplasms as well as identifying the best candidate patients for specific approaches.

Cell Communication↗