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PubMed1983

[Phase II study of vindesine in hematological malignancies].

A Phase II study of vindesine was carried out by the Vindesine Study Group in 130 patients with hematological malignancies: mainly 3 mg/body (about 2 mg/m2) of vindesine was administered once weekly by bolus injection. In 122 evaluable patients who had been heavily pretreated with vincristine and/or others, remissions were observed in patients with acute lymphocytic leukemia, blastic crisis of chronic myeloid leukemia, malignant lymphoma and other leukemias. The overall response rate was 39.3% including 20 complete and 28 partial remissions. No remissions were obtained in acute nonlymphocytic leukemia and multiple myeloma. All patients were evaluable for toxicity: Leukopenia occurred in 64.9%; peripheral neuropathy in 24.6%; GPT and GOT elevation in 20.7% and in 10.8%; alopecia in 11.5%; gastrointestinal disturbance in 10.8%; and fever in 5.4%. The treatment with vindesine was generally well tolerated, although in five out of 130 patients (3.8%) the treatment was discontinued due to convulsion, feeling of abdominal distention plus constipation, paralytic ileus, dysuria plus constipation, or interstitial pneumonia. Leukopenia and peripheral neuropathy appeared to be dose-limiting factors.

Adult↗

PubMed1995

Apoptin, a protein encoded by chicken anemia virus, induces cell death in various human hematologic malignant cells in vitro.

Apoptin, a small protein encoded by chicken anemia virus (CAV) was expressed in various human hematologic malignant cell lines derived from leukemias and lymphoma. Three of these cell lines contain bcl-2 or BCR-ABL proteins, known to block apoptosis induced by chemotherapeutic compounds. By immunofluorescence and propidium-iodide staining apoptin was shown to induce apoptosis in all analysed cell lines. Early after expression, apoptin exhibited a fine-granular distribution in the still intact nucleus. Later, apoptin became aggregated and the nucleus segmented. The data with truncated apoptin indicate that for optimal induction of apoptosis apoptin has to be located in the nucleus.

Apoptosis↗

PubMed1997

Supportive care in hematologic malignancies, including hematopoietic growth factors, transfusions, and infectious complications.

This review focuses on some of the recent developments in the field of supportive care in hematologic malignancies. The increasingly important role of hematopoietic growth factors in modern treatment modalities for hematologic disorders is clear. Newer developments in transfusional therapy and in the management of infectious complications are also discussed.

Blood Transfusion↗

PubMed2003

Molecular cytogenetic characterization of breakpoints in 19 patients with hematologic malignancies and 12p unbalanced translocations.

Structural rearrangements of the short arm of chromosome 12 are frequent cytogenetic findings in various hematologic malignancies. The ETV6 gene is the most common target for rearrangements in 12p13. Fluorescence in situ hybridization (FISH) investigations have shown that translocations of 12p other than t(12;21) are frequently accompanied by small interstitial deletions that include ETV6. Unbalanced translocations involving ETV6 have rarely been described, and breakpoints outside ETV6 appear to be strongly associated with complex karyotypes. We studied bone marrow samples from 19 patients known to have 12p unbalanced translocations and complex karyotypes, using FISH and spectral karyotyping. FISH analysis confirmed the hemizygous deletion of the ETV6 and CDKN1B genes in 74% of cases. We found four cases with interstitial deletions. In these four cases and in two others (6/19, 31.5%), the fusion with the partner chromosome was in the subtelomeric region of 12p13.3, confirming that there is a recurrent breakpoint in this region.

Adolescent↗

PubMedDate not supplied

Assessment of insertion techniques and complication rates of dual lumen central venous catheters in patients with hematological malignancies.

One hundred and twenty-three dual lumen silicone rubber central venous catheters were inserted into 101 patients with hematological malignancies undergoing intensive treatment. There was a perioperative complication rate of 13%. Open and closed techniques for inserting the catheter were compared. The operating time needed for introducing the catheter by the closed technique (average, 51 minutes) was significantly shorter (p less than 0.001) than the time needed for the open technique (70 minutes), whereas complication rates were equal in both techniques. On average, the catheters functioned for 149 days. Complications leading to removal were observed in 29.3% of patients, most of which were catheter-related infections (20.4%). Thromboembolic complications leading to removal were less frequent (4.1%) and appeared significantly earlier (p less than 0.001). These data indicate that introduction of the catheter by direct puncture of the subclavian vein is a quick and safe technique, and that this type of catheter is suitable for long-term use, both for infusion and for blood sampling.

Adolescent↗

PubMed2005

Outcome of patients with hematological malignancies admitted to the intensive care unit with life-threatening complications.

OBJECTIVE: To assess the outcome of patients with hematological malignancies (HM) admitted to medical intensive care unit (MICU) and to identify prognostic factors that may affect patients' outcome. METHODS: Data were collected in 44 patients with HM admitted to the MICU at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia within a 9-year period from 1993 to 2004. Demographic, physiological, clinical, laboratory and therapeutic data were collected on admission to MICU. RESULTS: Thirty-four percent of the patients had acute lymphocytic leukemia; 25% had acute myelocytic leukemia (AML) followed by non-Hodgkin's lymphoma in 20%, only 13.6% of these patients were in remission. The reasons for admission of these patients into MICU were shock (34.15%), respiratory failure (31.8%), cardiac arrest (20.4%), neurological causes (9.1%) and for other causes like small bowel perforation, hepatic failure, acute renal failure and metabolic disorders (4.5%). The overall in-hospital mortality was 72.7%, intensive care unit (ICU) mortality 61%, and the mean length of stay in the MICU was 5.4 +/- 4.8 days. A statistically significant association was demonstrated between both remission status and aspartate aminotransferase values on one side and patient's outcome on the other side. Patients with AML had poorer prognosis with mortality rate of 90.9%. CONCLUSION: Although mortality in patients with HM requiring ICU care is high, our results indicate that critical care support may be lifesaving. Apart from remission status and AML disease, no other prognostic factor could be identified.

Adult↗

PubMed2004

Acquired alpha-thalassemia in association with myelodysplastic syndrome and other hematologic malignancies.

Abnormalities of hemoglobin synthesis are usually inherited but may also arise as a secondary manifestation of another disease, most commonly hematologic neoplasia. Acquired hemoglobin disorders can be seen in any population and are not restricted to areas of the world with high incidences of inherited hemoglobinopathies. In fact, the acquired hemoglobinopathies may be more readily recognized where inherited hemoglobin abnormalities are rare and less likely to cause diagnostic confusion. Acquired alpha-thalassemia is the best characterized of the acquired red blood cell disorders in patients with hematologic malignancy, and it is almost always associated with a myelodysplastic syndrome (MDS). At least 2 molecular mechanisms for acquired alpha-thalassemia are now recognized: acquired deletion of the alpha-globin gene cluster limited to the neoplastic clone and, more commonly, inactivating somatic mutations of the trans-acting chromatin-associated factor ATRX, which cause dramatic down-regulation of alpha-globin gene expression. Here we review the clinical, hematologic, and molecular genetic features of alpha-thalassemia arising in a clonal myeloid disorder, and we discuss howATRX might affect gene expression in normal and abnormal hematopoiesis through epigenetic mechanisms.

Hematologic Neoplasms↗

PubMed1984

Chemical carcinogenesis. A soil fumigant, 1,3-dichloropropene, as possible cause of hematologic malignancies.

Findings from three case reports suggest a causal relationship between exposure to a soil fumigant , 1,3- dichloropropene , and hematologic malignancy. Its chemical relationship to other carcinogens is noted. The purpose of this report is to record this evidence and alert physicians that prior exposure to this chemical of patients initially observed with neoplasms should be noted in the medical history.

Adult↗

PubMed1995

Single-cell trisomy in hematologic malignancy. Random change or tip of the iceberg?

Finding a clone in the bone marrow of a patient with a hematologic disorder is important to confirm the neoplastic nature of the disease and may be indicative of prognosis. Since cytogenetic analysis detects only actively dividing clones, the presence of a single abnormal cell among 20 cells analyzed raises doubts about its clonal nature. Fluorescence in situ hybridization (FISH) enables rapid detection of certain chromosomal abnormalities in metaphase and interphase cells, thus enabling detection of minor or inactive clones. Seven patients with hematologic malignancy each having random cell(s) were investigated thus: at diagnosis, with MDS and a cell with +8 (two cases) or +9 (one case) and with AML and a cell with +4 (one case), +7 (one case), or two cells with +9, +22/ +10, +17, +17 (one case). One patient with ALL in remission had one cell with trisomy 4. One patient, a male aged 66 years with refractory anemia with ringed sideroblasts, was found to have a minor trisomy 8 clone in his diagnostic marrow. A follow-up marrow 42 months later showed no trisomy 8 cell among 62 metaphases analyzed, and the percentage of trisomic cells using FISH on interphase cells was within the control range. This patient has survived for more than 42 months requiring no treatment. Single-cell abnormalities in the other six cases proved to be random events. Thus it appears that single-cell abnormalities may not be clonal or at most indicate the presence of a minor clone well below the level of cytogenetic detection. The prognostic significance of such minor clones is at present unclear.

Adult↗

PubMed2006

Modulation of the systemic inflammatory response by recombinant human interleukin-11: a prospective randomized placebo controlled clinical study in patients with hematological malignancy.

The immunomodulatory activities of recombinant human interleukin-11 (rhIL-11) were investigated in a clinical trial among patients with hematological malignancy, randomized to either rhIL-11 or placebo throughout chemotherapy. Daily serum concentrations of sTNFRI, IL-6, IL-8, TNFalpha, and CRP were measured. Higher sTNFRI levels [mean pg/ml (95% CI)] were detected in patients receiving rhIL-11 compared to placebo [1749.7 (1626-1882.9) versus 1038.5 (953.3-1131.3)] respectively (P = 0.01) for all 898 observations and during febrile days [2327.6 (2142.6-2528.2) versus 1308.9 (1163-1473.2), P = 0.12] and during days without infection [1406.6 (1266.1-1563) versus 871.3 (774.9-979.6), P < 0.001]. A similar pattern in CRP concentrations was observed. Multivariate analysis indicated rhIL-11 was associated with elevated sTNFRI or CRP independent of infectious episodes and other factors. 7 patients (all receiving placebo) of 40 had elevated TNFalpha levels. IL-6 and IL-8 levels were not substantially affected by rhIL-11. Bacteremia, fungal infections, and fever of unknown origin (FUO) were reduced in rhIL-11-treated patients. Given the role of sTNFRI in dampening the deleterious effects of a hyperactive TNFalpha environment, rhIL-11-induced upregulation of sTNFRI shedding is a potentially important mechanism for modulating immune and inflammatory responses in humans.

Adolescent↗

PubMed1994

The role of autologous hematopoietic stem cell transplantation in hematologic malignancy.

Supraintensive cytoreductive therapy with hematopoietic stem cell rescue (HSCR) is able to provide curative therapy in a number of hematologic malignancies. Allogeneic HSCR is limited to less than 50% of patients because of the absence of related or unrelated compatible donors. Autologous HSCR is a viable alternative to allogeneic HSCR and is applicable to a greater number of patients. In addition, because of the absence of graft-versus-host disease, it is applicable to older patients. Although the relapse of malignancy is higher following autologous compared with allogeneic marrow, the disease-free survival for autologous HSCR is often equal to or greater than that seen following allogeneic HSCR. A number of posttransplantation immunological based therapies have shown promise for further decreasing the relapse rate following autologous HSCR.

Hematopoietic Stem Cell Transplantation↗

PubMed1988

Bacteremia and candidemia in hematological malignancies: microbiological findings and antibiotic susceptibilities.

The microorganisms isolated in 1981-1985 from 171 cases of septicemia in patients with hematological malignancies were on the whole the same as those found in 1970-1972. The distribution between species was also quite similar for the two periods except within staphylococci, where the isolation rate of coagulase-negative staphylococci was higher in the latter period while that of Staphylococcus aureus was lower. Of 67 strains of Enterobacteriaceae tested for an aminoglycoside, 6% were found to be resistant, whereas 8% of 48 Enterobacteriaceae strains were found to be cefotaxime resistant. Methicillin- or aminoglycoside resistant S. aureus did not occur.

Candidiasis↗

PubMed2005

[Reduced intensity of BuCy conditioning regimen for transplantation in the treatment of malignant hematologic diseases].

OBJECTIVE: To evaluate the use of a new reduced intensity of BuCy conditioning regimen for the treatment of malignant hematologic diseases in aged or intolerable patients receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) from the siblings. METHODS: Twelve patients with acute lymphoblastic leukemia (ALL, n = 4), acute myelogenous leukemia (AML-M(2), n = 2), chronic myelogenous leukemia (CML, n = 4), and myelodysplastic syndromes-refractory anemia with excess blasts (MDS-RAEB, n = 2) were intolerant of conventional myeloablative therapy because of age (older than 50 years) or having severe concurrent diseases. The median age was 49 years (range 42-64 years). Seven were males and five females. Two of the 12 patients were HLA one antigen-mismatched and the rest HLA identical with their donors. The low dosage conditioning regimen consisted of busulfan (2 mg.kg(-1).d(-1) for 3 days), Ara-C (2 g.m(-2).d(-1) for 1 or 2 times), cyclophosphamide (1.0 g.m(-2).d(-1) for 2 days) and anti-T-lymphocyte globulin (ATG 2.5 mg.kg(-1).d(-1) for 4 days, -5 - -2 day). Granulocyte colony-stimulating factor mobilized bone marrow and peripheral blood stem cells (PBSC) were harvested (1 patient using PBSC alone). All patients received cyclosporin A, short-term MTX and mycophenolate mofetil (MMF) for prophylaxis of acute graft-versus-host disease (aGVHD). DNA short tandem repeat (STR) sequence analysis, cytogenetics and molecular-biologic technique were used to analyze chimerism. RESULTS: All the patients were well tolerated the regimen, with no severe regimen related toxicity. In all the 12 patients, absolute neutrophil count > or = 0.5 x10(9)/L was achieved in 11 to 17 (median 15) days and platelet count > 20 x 10(9)/L in 10 to 23 (median 15) days after transplantation. Complete chimerism was achieved in 11 patients and 1 patient was in mixed chimerism at one month after HSCT. With a median follow-up of 14.5 (4.0-24.0) months, 7 of the 12 patients (58.0%) were alive and 5 (42.0%) of the 7 were disease-free. The probabilities of OS and DFS at 12 months were 75.0% and 48.1%. Five patients (41.6%) had aGVHD and four had local chronic GVHD with a cumulative probability of chronic GVHD of 41.5%. CONCLUSION: This reduced intensity conditioning regimen is well tolerated and safe for HSCT in the older patients or patients with severe concurrent medical conditions and can achieve full chimerism and long-term disease-free survival.

Adult↗

PubMed1991

[Timing of administration of granulocyte colony stimulating factor after cytotoxic chemotherapy in hematological malignancies].

We evaluated the effects of recombinant human granulocyte colony stimulating factor (rhG-CSF) given to 30 patients with hematological malignancies after cytotoxic chemotherapy. The first course of chemotherapy was not treated with rhG-CSF (control), and in the second to fourth courses, rhG-CSF was given by one of the following three ways to the patients (not necessarily in this order): 1) 10 days of administration starting 48 hr after chemotherapy, 2) 5 days of administration starting 48 hr after chemotherapy, and 3) 5 days of administration after the leukocyte counts reached to less than 2,000/microliters. The leukocyte nadirs were significantly higher in the course with 10 days of administration compared with the control course. The time needed for recovery from the leukocyte nadir was significantly shorter in 10-day course and 5-day course after the leukocyte counts reached to less than 2,000/microliters. The therapy spans became significantly shorter with all of the three patterns of administration of rhG-CSF compared with the control course. The number of days on which the leukocyte counts became less than 2,000/microliters were significantly fewer in 10-day course and 5-day course after the leukocyte counts became less than 2,000/microliters. These findings showed that rhG-CSF prevented severe neutropenia after cytotoxic chemotherapy, and (or) assisted the rapid recovery from neutropenia. These effects depend on the timing of its administration.

Acute Disease↗

PubMed1991

[Plasma concentrations of plasminogen activator inhibitor 2 in patients with hematological malignancies and their clinical significance].

We investigated plasma levels of plasminogen activator inhibitor 2 (PAI-2) in 40 patients with hematological malignancies including acute leukemia, chronic leukemia, hemophagocytic histiocytosis (HH) and histiocytic sarcoma (HS). The plasma PAI-2 levels in the patients with mononuclear phagocyte system (MPS) proliferative disorders (M4, M5, and CMMoL on FAB classification, HH and HS) were all above the cut-off value in healthy subjects. In a patient of reactive HH, there was a close correlation between Plasma PAI-2 and serum ferritin levels during the clinical course. These results indicate that the increase of plasma PAI-2 would be a diagnostic indicator of MPS proliferative disorders.

Adult↗

PubMed1984

Ribonucleotide reductase and thymidine kinase activities in various cultured cell lines derived from hematologic malignancies.

The activities of ribonucleotide reductase and thymidine kinase, and the thymidine incorporation rate were measured in 16 cultured human hematologic malignant cell lines with different cell proliferation rates. Thymidine kinase activity was significantly higher in myeloid and monocytoid cell lines than in other cell lines, but ribonucleotide reductase activity presented as CDP reductase activity was similar in the different cell lines. The ratio of thymidine kinase to CDP reductase activity was high in monocytoid cell lines. A close correlation was found between the cell proliferation rate and CDP reductase activity, but not thymidine kinase activity or the thymidine incorporation rate. The ratio of thymidine kinase to CDP reductase activity was high in slowly growing cell lines and low in rapidly growing cell lines. These results indicate that in cultured human malignant cells a high potential for proliferation may depend mainly on the de novo pyrimidine pathway of DNA biosynthesis.

Adolescent↗

PubMed1993

The importance of impedance cardiography in monitoring cardiac function in patients with hematological malignancies.

Cardiac function was monitored by means of impedance cardiography in the early phase of chemotherapy in 30 patients with hematological malignancies. The patients were divided into two groups according to whether or not they revealed cardiac risk factors (age > 65, coronary heart disease, cardiac failure, hypertension, diabetes mellitus or prior mediastinal irradiation). It was found that the mean values of cardiac and stroke indices before chemotherapy were significantly lower in patients with cardiac risk factors. It was also noted that the mean values of these indices in both groups did not change significantly after anticancer treatment. However, in two patients a significant decrease of cardiac indices was observed. On the other hand, in several patients an increase of cardiac and stroke indices was recorded. It seems that careful measurements of cardiac function in cancer patients by impedance cardiography enable to analyze the influence of anticancer drugs upon the cardiovascular system. The results of these measurements may be used for the individualization of cancer therapy.

Adult↗

PubMed2006

Compound heterozygosity for two MSH6 mutations in a patient with early onset of HNPCC-associated cancers, but without hematological malignancy and brain tumor.

Heterozygous germline mutations in the human mismatch repair (MMR) genes MLH1, PMS2, MSH2 and MSH6 predispose to the hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Biallelic mutations in these genes have been reported for a limited number of cases resulting in hematological malignancies, brain tumors and gastrointestinal tumors early in childhood. These tumor phenotypes are frequently associated with café-au-lait spots (CALS), one of the clinical hallmarks of neurofibromatosis type 1 (NF1). We report the first case of compound heterozygosity for two MSH6 mutations resulting in a nonconservative amino-acid change of a conserved residue and in a premature stop codon in a patient who developed rectal and endometrial cancer at ages 19 and 24 years, respectively, and presented few CALS in a single body segment. Immunohistochemistry and Western blotting revealed only residual expression of the MSH6 protein in the normal cells. The disease history resembles the HNPCC phenotype rather than a phenotype associated with biallelic MMR gene mutations. Therefore, we assume that one or both mutations abolish protein function only partially, further supported by the parents, which are both carriers of one of the mutations each, and not affected by the disease at ages 57 and 58 years. Our data suggest considering biallelic mutations in MMR genes for patients who develop HNPCC-associated tumors at an unusually young age of onset, even without hematological or brain malignancies.

Adult↗