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PubMed2001

Angiogenesis in hematologic malignancies.

Angiogenesis, defined as the blood vessel generation from preexisting blood vessels, was found to play an important role in the progression of solid tumors. In addition, bone marrow-derived endothelial precursor cells may contribute to tumor angiogenesis. Recently angiogenesis induction was described in several hematologic neoplasms as leukemia, lymphoma, myelodysplastic syndrome and multiple myeloma (MM). Clinical angiogenesis research also termed as angiodiagnosis has established the prognostic relevance of markers of angiogenesis e.g., microvessel density and circulating levels of angiogenic peptides. Development of antiangiogenic treatment for hematologic neoplasms has recently been sparked by the success of Thalidomide (Thal) which has antiangiogenic properties in MM. Antiangiogenic treatment strategies are now being tested in clinical trials on several types of hematologic neoplasms.

Angiogenesis Inhibitors↗
PubMed1995

[The value of the parathyrin-related protein (PTH-RP) in the diagnosis of cancer-associated hypercalcemia].

BACKGROUND: The parathyrine related protein (PTH-RP) is very similar, both in structure and in function, to the PTH and is considered as a mediator in humoral hypercalcemia in cancer. The aim of this study was to know the clinical value of PTH-RP measurement. METHODS: Serum PTH-RP concentrations were studied in 22 healthy subjects, 13 patients with primary hyperparathyroidism, 9 patients with solid neoplasms and normocalcemia, 26 patients with solid neoplasms and hypercalcemia and 4 patients with hematologic neoplasms and hypercalcemia. The PTH-RP was quantified by a competitive radioimmunoassay technique using a specific antibody of the PTH-RP 1-40 fragment. Intact parathyrine (i-PTH) was quantified by an IRMA method using 2 polyclonal antibodies (INCSTAR). RESULTS: Fifteen (68%) of the healthy controls presented undetectable serum PTH-RP concentrations. The serum PTH-RP concentration was normal in all those patients with hyperparathyroidism. Elevated serum PTH-RP values were not found in patients with solid neoplasms and normocalcemia or in those with hematologic neoplasms and hypercalcemia. High values of PTH-RP were observed in 8 out of 9 (88%) of the patients with solid neoplasms and hypercalcemia with bone metastasis and in 7 out of 11 (63%) of the patients with bone involvement. CONCLUSIONS: Serum parathyrine-related protein was found to be high in a large proportion of patients with solid neoplasms and hypercalcemia. Serum PTH-RP determination is useful in the clinical investigation of patients with hypercalcemia. Even in patients with bone metastasis, hypercalcemia may have a humoral background.

Adult↗
PubMed1999

Insect bite-like reaction in patients with hematologic malignant neoplasms.

BACKGROUND: Exaggerated reaction to insect bites, mainly to mosquitoes, is infrequently described in patients with chronic lymphocytic leukemia. Skin lesions usually appear months to years after the diagnosis of leukemia and are unrelated to laboratory findings, disease course, or therapy. OBSERVATIONS: We describe 8 patients with various hematologic disorders (chronic lymphocytic leukemia, acute lymphoblastic leukemia, acute monocytic leukemia, mantle-cell lymphoma, large-cell lymphoma, and myelofibrosis) who developed insect bite-like reaction. Although the clinical picture and the histological characteristics of the lesions were typical for insect bites, none of the patients actually had a history, course, or response to treatment suggestive of arthropod assaults. In 2 patients, the eruption preceded the diagnosis of the malignant neoplasm. The rash persisted for months to years and was resistant to therapies other than systemic corticosteroids. The 3 patients with chronic lymphocytic leukemia seemed to have a worse prognosis than expected for their disease. In 1, the polymerase chain reaction detected leukemic cells in the infiltrate. CONCLUSIONS: Insect bite-like reaction is an infrequent, disturbing, and difficult-to-treat nonspecific phenomenon in patients with hematologic malignant neoplasms. Since it may precede the hematologic disorder, oriented evaluation is warranted. We speculate that immunodeficiency plays a role in its pathogenesis; however, the exact pathogenesis and its prognostic implications await further studies.

Adolescent↗
PubMed2005

Dido gene expression alterations are implicated in the induction of hematological myeloid neoplasms.

The myelodysplastic/myeloproliferative diseases (MDS/MPDs) are a heterogeneous group of myeloid neoplasms that share characteristics with chronic myeloproliferative diseases and myelodysplastic syndromes. The broad spectrum of clinical manifestations makes MDS/MPDs extremely difficult to diagnose and treat, with a median survival time of 1-5 years. No single gene defect has been firmly associated with MDS/MPDs, and no animal models have been developed for these diseases. The association of deletions on chromosome 20q with myeloid malignancies suggests the presence of unidentified tumor suppressor genes in this region. Here we show that the recently identified death inducer-obliterator (Dido) gene gives rise to at least 3 polypeptides (Dido1, Dido2, and Dido3) through alternative splicing, and we map the human gene to the long arm of chromosome 20. We found that targeting of murine Dido caused a transplantable disease whose symptoms and signs suggested MDS/MPDs. Furthermore, 100% of human MDS/MPD patients analyzed showed Dido expression abnormalities, which we also found in other myeloid but not lymphoid neoplasms or in healthy donors. Our findings suggest that Dido might be one of the tumor suppressor genes at chromosome 20q and that the Dido-targeted mouse may be a suitable model for studying MDS/MPD diseases and testing new approaches to their diagnosis and treatment.

Alternative Splicing↗
PubMed2005

Immunohistochemistry in bone marrow pathology: a useful adjunct for morphologic diagnosis.

Pathomorphological examination of trephine biopsies of the bone marrow (BM) represents a standard method for the diagnosis and staging of hematologic neoplasms and other disorders involving the BM. The increasing knowledge about the genetic basis and biology of hematologic neoplasms, as well as the recently proposed WHO classification system, provide the framework for an accurate diagnosis. Although conventional morphology remains the gold standard for paraffin-embedded BM trephines, immunohistochemical stainings have become an integral part of the diagnostic workup. Antibodies suitable for paraffin sections are generally applicable to BM trephines, but modifications of staining protocols may be necessary due to the alternative fixatives and decalcification procedures used for BM biopsies. The indications for immunostainings range from confirmation and classification of lymphoma involvement, subclassification of acute leukemias, and estimating blast counts in myelodysplastic and myeloproliferative syndromes to characterization of BM involvement in nonhematologic neoplasms. Although subtyping of NHL in the BM is more difficult from the point of morphology, classification of the entities that frequently involve the BM, especially the small B-cell lymphomas, can easily be achieved with the help of immunohistochemistry. In this review, we try to summarize the current state of the art in BM immunohistochemistry for the diagnosis of hematologic disorders. Moreover, diagnostic algorithms and useful antibody panels are proposed for a rational and cost-effective approach.

Algorithms↗
PubMed2005

Elevated levels of soluble interleukin-2 receptor in serum of patients with hematological or non-hematological malignancies.

We measured the levels of soluble interleukin-2 receptor (sIL-2R) in the serum of 53 patients with hematological malignancies (14 with acute leukemia, 10 myeloproliferative disorders, 21 non-Hodgkin's lymphoma and 8 multiple myeloma), 40 with non-hematological solid malignancies (24 with lung cancer, 11 digestive system cancer and 5 other cancers) and 95 healthy subjects as a control using an enzyme-linked immunosorbent assay. Both hematological and non-hematological neoplasms showed significantly higher sIL-2R levels than normal subjects (p<0.01). However, compared to solid malignancies, hematological neoplasms displayed a wide range of sIL-2R levels and extremely elevated values of sIL-2R were seen in certain cases. These results seem to suggest that sIL-2R levels may serve as one of non-invasive markers of differential diagnosis for patients with bulky mass lesions between hematological and solid malignancy.

Adolescent↗
PubMed2004

Testicular function following chemo-radiotherapy.

Improvements in cancer survival raise infertility issues in young patients suffering from malignancies. The aim of the study is to review current knowledge on the effect of chemotherapy (CT) and radiotherapy (RT) for testis and hematological neoplasms on testicular function. Cisplatin-based regimens for testis neoplasm induce temporary azoospermia; permanent damage can occur with high doses (400-600 mg/m(2)). Alkylating agents are very effective for hematological neoplasm therapy but extremely dangerous to germinal epithelium. Damage can be irreversible. Spermatozoa cannot tolerate irradiation doses higher than 6 Gy. Leydig cells are damaged by doses higher than 15 Gy. A-Spermatogonia have been shown to survive after CT and RT and their recovery for post-treatment graft has been recently developed in animal models. Infertility counselling before treatment in young oncological patients is mandatory. Cryopreservation is the best option for fertility protection.

Animals↗
PubMed2004

[Agranular CD4+ CD56+ hematodermic neoplasm: a new case report].

BACKGROUND: "Agranular CD4+ CD56+ hematodermic neoplasm" are rare hematologic neoplasms which were recently shown to correspond to the plasmocytoid dendritic cells. CASE REPORT: A 83-year-old presented isolated skin lesions purple, infiltrating the dermis. The biopsy has shown a dense dermal infiltration with malignant cells CD4+ CD56+ CD43+. There were no bone marrow involvement and no circulating blood cells. A chemotherapy permitted a clinical remission after six courses. Unfortunately, skin and blood relapses appear four months later. After a short success of chemotherapy by DHAP, the patient died three month later. DISCUSSION: "Agranular CD4+ CD56+ hematodermic neoplasm" is a distinct entity from the cutaneous primary lymphomas. Recently plasmocytoid monocyte cells have been identified as the precursor of the malignant population with the high expression of CD123, IL3 receptor. It is a distinct clinicopathologic entity by its clinical presentation with skin tropism, bone marrow involvement with or without leukemic phase and poor prognosis independent of the kind of treatment and its particular phenotype CD4+ CD56+ CD43+. It would be interesting to use antibodies linked to CD123 in therapeutic because any treatment have efficacity in this disease.

Aged↗
PubMedDate not supplied

Skin manifestations in CD4+, CD56+ malignancies.

CD4+ CD56+ hematologic neoplasms were recently individualized. We report three cases of CD4+ CD56+ malignancies with cutaneous lesions in three cases and also bone marrow involvement in two cases. Two patients relapsed 2 and 3 months after polychemotherapy. Two patients died within 3-10 months. A constant immunophenotype was observed with the co-expression of CD4 and CD56, the absence of B and T-cell markers. The salient fact of this report is the presence of T-cell clonal rearrangement. The clinical and pathological features closely resemble the specific cutaneous manifestations in acute leukemia with monocytic differentiation, especially the granulocytic sarcoma. Because of the positivity of the CD56, natural killer cell proliferations were discussed. Since 1994, 50 cases of CD4+, CD56+ cutaneous neoplasms have been reported with specific clinical, cytologic and immunohistochemical features. The diagnosis is more difficult when the cutaneous location is exclusive; on the contrary, the cytological features of the blood and medullar cells with cytoplasmic vacuoles and pseudopodia are characteristic of this hematologic neoplasm. The presence of CD123 antigen in most of the cases is an argument for a plasmacytoid dendritic cell proliferation and it is also a good marker for primary cutaneous lesions.

Aged↗
PubMed1998

Evaluation by multivariate analysis of the differentiation inhibitory factor nm23 as a prognostic factor in acute myelogenous leukemia and application to other hematologic malignancies.

The differentiation inhibitory factor nm23 can inhibit the differentiation of murine and human myeloid leukemia cells. We recently reported that nm23 genes were overexpressed in acute myelogenous leukemia (AML), and a higher level of nm23-H1 expression was correlated with a poor prognosis in AML, especially in AML-M5 (acute monocytic leukemia). To evaluate the importance of nm23 expression as a prognostic factor in AML, we compared it with other putative prognostic factors in AML. An analysis of the correlation between nm23 expression and the clinical parameters of 110 patients with AML demonstrated that increased nm23-H1 mRNA levels were associated with resistance to initial chemotherapy and with reduced overall survival. Multivariate analysis using Cox's proportional hazard model also showed that elevated nm23-H1 mRNA levels significantly contributed to the prognosis of patients with AML. Especially in AML-M5, nm23-H1 status was the most important prognostic factor. Furthermore, to determine whether we can apply the results observed in AML to other hematologic malignancies, we investigated the relative levels of nm23-H1 and nm23-H2 transcripts in 149 patients with hematologic neoplasms, including 110 with de novo AML, 9 with de novo acute lymphoblastic leukemia, 14 with myelodysplastic syndrome, 16 with chronic myelogenous leukemia (CML), and 5 normal subjects by the reverse transcriptase-polymerase chain reaction. Expression of nm23-H1 was significantly higher in all the hematologic neoplasms, except CML in chronic phase, than in normal blood cells. nm23 may have a prognostic effect in these hematologic malignancies as well as in AML.

Acute Disease↗
PubMed2005

JAK2 mutation 1849G>T is rare in acute leukemias but can be found in CMML, Philadelphia chromosome-negative CML, and megakaryocytic leukemia.

An activating 1849G>T mutation of JAK2 (Janus kinase 2) tyrosine kinase was recently described in chronic myeloproliferative disorders (MPDs). Its role in other hematologic neoplasms is unclear. We developed a quantitative pyrosequencing assay and analyzed 374 samples of hematologic neoplasms. The mutation was frequent in polycythemia vera (PV) (86%) and myelofibrosis (95%) but less prevalent in acute myeloid leukemia (AML) with an antecedent PV or myelofibrosis (5 [36%] of 14 patients). JAK2 mutation was also detected in 3 (19%) of 16 patients with Philadelphia-chromosome (Ph)-negative chronic myelogenous leukemia (CML), 2 (18%) of 11 patients with megakaryocytic AML, 7 (13%) of 52 patients with chronic myelomonocytic leukemia, and 1 (1%) of 68 patients with myelodysplastic syndromes. No mutation was found in Ph(+)CML (99 patients), AML M0-M6 (28 patients), or acute lymphoblastic leukemia (20 patients). We conclude that the JAK2 1849G>T mutation is common in Ph(-) MPD but not critical for transformation to the acute phase of these diseases and that it is generally rare in aggressive leukemias.

Humans↗
PubMed2002

[Use of intravenous immunoglobulin in treatment of neoplasms and hematologic disorders in children].

Immunoglobulins are an important component of the immune system and of the host defense against infection. They are also important in immune regulation. The intravenous immunoglobulins has been proven beneficial in prophylaxis and treatment of infections in patients with primary and secondary immunodeficiency. Many studies confirmed the efficacy of IVIG in the treatment of idiopathic thrombocytopenic purpura and other autoimmune disorders. In the last years monoclonal antibodies were included to anticancer therapy in children and adults.

Autoimmune Diseases↗
PubMed1977

Second malignancies in patients with multiple myeloma.

Seven patients with multiple myeloma who developed a second neoplasm are presented. There were four patients with acute leukemia and three patients with non-hematologic neoplasms. The patients with acute leukemia were among the longest survivors (median duration approximately 72 months) and the response to anti-leukemic therapy in these patients was generally poor. Of the three patients with non=hematologic neoplasms, one patient was observed with simultaneous renal cell carcinoma and the other two patients developed adenocarcinoma of the colon and lung subsequently. In addition, two patients with mammary carcinoma who subsequently developed multiple myeloma were included. Literature was reviewed and the possibility that multiple myeloma itself might be a risk factor for the development of other malignancies was discussed.

Adenocarcinoma↗
PubMed2000

Plasma levels of the differentiation inhibitory factor nm23-H1 protein and their clinical implications in acute myelogenous leukemia.

A previous study reported that a nondifferentiating myeloid leukemia cell line produced differentiation-inhibiting factors. One of the factors was purified as a homologue of the nm23 genes. The nm23 genes were overexpressed in acute myelogenous leukemia (AML) cells, and a higher level of nm23 gene expression was correlated with a poor prognosis in AML. The present study determined the plasma levels of nm23-H1 protein by enzyme-linked immunosorbent assay and assessed the association between this level and the clinical outcome in 102 patients with AML. The plasma concentration of nm23-H1 was higher in patients with AML than in normal controls (P =.0001). Plasma nm23-H1 levels were correlated with the product of the intracellular nm23 messenger RNA (mRNA) level and the white blood cell count, but not with the mRNA level alone. Therefore, nm23-H1 plasma levels probably depend on the total mass of leukemic cells overexpressing the nm23-H1 gene. Overall survival was lower in patients with higher plasma nm23-H1 levels than in those with lower levels. Multivariate analysis using the Cox proportional hazard model showed that elevated plasma nm23-H1 levels significantly contributed to the prognosis of AML patients. Furthermore, the plasma nm23-H1 levels were investigated in 70 patients with other hematologic neoplasms, including 6 with acute lymphoblastic leukemia, 13 with chronic myelogenous leukemia, and 12 with myelodysplastic syndrome. Plasma nm23-H1 levels were significantly higher in all of these hematologic neoplasms than in normal controls. Increased plasma levels of nm23-H1 may have prognostic value in these hematologic malignancies as well as in AML.

Adult↗
PubMed1983

Evaluation of a radioimmunoassay for alpha 1-acid glycoprotein to monitor therapy of cancer patients.

A new radioimmunoassay for alpha 1-acid glycoprotein (AGP) for monitoring the therapy of cancer patients was evaluated. Plasma levels of this glycoprotein were measured in 49 normal healthy volunteers, 71 patients with illnesses other than cancer, 190 patients with solid tumors, and 58 patients with hematologic neoplasms. Plasma levels of AGP were elevated in 89% of the solid tumor patients and 87% of the patients with hematologic neoplasms who had newly diagnosed, locally recurrent, or metastatic cancer. Only 18% of patients with illnesses other than cancer and normal renal function had elevations of plasma AGP. Serial measurements of AGP may be useful for monitoring therapy in several tumor types, including small-cell lung cancer, colon cancer, lymphoma, and non-small-cell lung cancer.

Evaluation Studies as Topic↗
PubMed2004

Second allogeneic bone marrow transplantation after myeloablative conditioning analysis of 43 cases from single institution.

Between March 1984 and December 1999, a total of 43 second related allogeneic BMT procedures after myeloablative conditioning were carried out in our institution, 37 following allogeneic, and 6 following autologous BMT. Thirty one patients were males (72%). At 1st BMT (BMT1), median age was 11.5 years (range, 0.16-45 years). BMT1 was carried out for the diagnosis of AML in 13 patients (30%), SAA in nine (21%), ALL in six (14%), CML in six (14%), immunodeficiency in three (7%), NHL in two, beta-thal in two, HD in one, Red cell aplasia in one. HLA matching status for allogeneic BMT1 was full match in 33, one antigen mismatch in two and haplo identical in two patients. Median age at the 2nd BMT (BMT2) was 14 years (range, 0.41-46.7 years). Indications for BMT2 were recurrent hematologic neoplasm in 23 patients (53%), primary graft failure in 12 (28%) and late graft failure in 8 (19%). Median time from BMT1 to recurrence of hematologic neoplasm or late graft failure was 10 months (range, 2.5- 88 months). Median BMT1 to BMT2 interval was 13 months (range, 1-107 months). For BMT2, the same donor was used in 29 patients, while 14 patients had alternate related donor (12 full match, 1-one Ag mismatch, 1 haplo identical). A different conditioning regimen was used in the majority of the patients (39, 91%). Radiation containing conditioning regimen were used mostly for patients previously conditioned with chemotherapy only for BMT1 and chemotherapy conditioning +/- ATG for those who received radiation containing conditioning at BMT1. Bone marrow was the stem cell source for all patients at BMT2 and all except three autologous peripheral stem cell transplantation patient at BMT1. Significant organ toxicity leading to procedure related death in 13 patients (30%) was observed after BMT2. At a median follow up of 36 months after BMT2, 22 patients (51%) are alive (20 free of disease, 2 with recurrent disease) with overall median survival of 47.5 (SD +/- 9) months. Univariate analysis of relevant clinical factors identified the following variables as the only statistically significant favorable prognostic factors for overall survival: BMT1-BMT2 interval of > or = 6 months (P=0.0007) and age at BMT2 < or = 10 years (P=0.041). The nature of underlying disease (neoplastic or non-neoplastic) was not statistically significant (P=0.23). There was no statistically significant difference in survival outcome of BMT2 using same donor vs. alternate related donor (P=0.51). Due to the relatively limited sample size, multivariate analysis was not attempted. This single institution study suggests that second allogeneic BMT after myeloblative conditioning has an acceptable treatment related morbidity/mortality and favorable outcome if performed at age < or = 10 years and with an interval of > or = 6 months after the first BMT. Additionally same donor can successfully be used for the second transplant with similar survival outcome to alternate donor.

Adolescent↗
PubMed1987

Cancer mortality of capacitor manufacturing workers.

Experimental studies have demonstrated that certain types of commercially produced polychlorinated biphenyls (PCBs) are carcinogenic. Data in humans are still controversial. This study was undertaken in order to determine possible long-term effects, particularly cancer, in workers engaged in the manufacture of capacitors impregnated with PCBs in a plant operating since 1946. All workers employed for at least 1 week between 1946 and 1978 were admitted to the study (544 males and 1,556 females), and their mortality was examined for the period 1946-1982. Data on environmental contamination, workers' PCBs intake, and health effects (chloracne) were available, which documented the general exposure conditions in the plant. Vital status was ascertained for over 99% of the subjects, and death certificates were obtained for all deceased persons. Expected deaths were calculated using two sets of mortality rates, national and local. Among male workers, cancer deaths (14 obs.) were significantly increased as were deaths owing to cancer of the gastrointestinal (GI) tract (6 obs.). Also, mortality from hematologic neoplasms (3 obs.) and lung cancer (3 obs.) was higher than expected; however, the excess was statistically not significant. Female workers exhibited an overall mortality that was significantly increased above expectations. Cancer deaths (12 obs.) and hematologic neoplasms (4 obs.) were significantly higher than expected when compared with the local population. Interpretation of the results is limited by the small number of deaths; however, the point of interest is the consistency of these results with previous experimental and epidemiologic studies, which indicated the GI tract and lymphatic and hemopoietic tissue as the most probable target sites of the PCBs carcinogenic activity.

Digestive System Neoplasms↗