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PubMed1989

Effect of HLA compatibility on engraftment of bone marrow transplants in patients with leukemia or lymphoma.

We analyzed the relevance of HLA compatibility to sustained marrow engraftment in 269 patients with hematologic neoplasms who underwent bone marrow transplantations. Each patient received marrow from a family member who shared one HLA haplotype with the patient but differed to a variable degree for the HLA-A, B, and D antigens of the haplotype not shared. These 269 patients were compared with 930 patients who received marrow from siblings with identical HLA genotypes. All patients were treated with cyclophosphamide and total-body irradiation followed by the infusion of unmodified donor marrow cells. The rate of graft failure was 12.3 percent among the recipients of marrow from a donor with only one identical haplotype, as compared with 2.0 percent among recipients of marrow from a sibling with the same HLA genotype (both haplotypes inherited from the same parents) (P less than 0.0001). The incidence of graft failure correlated with the degree of donor HLA incompatibility. Graft failure occurred in 3 of 43 transplants (7 percent) from donors who were phenotypically HLA-matched with their recipient (haplotypes similar, but not inherited from the same parents), in 11 of 121 donors (9 percent) incompatible for one HLA locus, in 18 of 86 (21 percent) incompatible for two loci, and in 1 of 19 (5 percent) incompatible for three loci (P = 0.028). In a multivariate binary logistic regression analysis, independent risk factors associated with graft failure were donor incompatibility for HLA-B and D (relative risk = 2.1; 95 percent confidence interval, 1.7 to 2.5; P = 0.0004) and a positive crossmatch for anti-donor lymphocytotoxic antibody (relative risk = 2.3; 95 percent confidence interval, 1.8 to 2.8; P = 0.0038). Residual host lymphocytes were detected in 11 of 14 patients with graft failure, suggesting that the mechanism for graft failure could be host-mediated immune rejection. We conclude that donor HLA incompatibility and prior alloimmunization are significant risk factors for graft failure, and that a more effective immunosuppressive regimen than those currently used is needed for consistent achievement of sustained engraftment of marrow transplanted from donors who are not HLA-identical siblings.

Adolescent↗

PubMed1990

Relation of cytogenetic abnormalities and clinical outcome in metastatic melanoma.

The value of chromosomal analysis is well established in human hematologic neoplasms. In contrast, the relation between chromosomal abnormalities and clinical outcome in solid tumors in humans has received little study. We undertook this study to determine whether chromosomal abnormalities could provide information on the survival of patients with malignant melanoma. Chromosome-banding analysis was performed on tumor-biopsy samples from 62 patients with metastatic melanoma, and recurring cytogenetic abnormalities were correlated with survival. Patients with structural abnormalities of chromosome 7 or 11 had significantly shorter survival than patients without these abnormalities. We conclude that cytogenetic analysis may provide useful prognostic information about patients with metastatic melanoma.

Chromosome Aberrations↗

PubMed2005

Organisation of neoplastic haematopathology services: a UK perspective.

The diagnosis of haematological malignancies has begun to emerge as a distinct pathological discipline in the United Kingdom. This has been driven by the recommendation of the National Institute for Clinical Excellence that diagnosis of leukaemia and lymphoma should take place in a specialist laboratory and in most cases this should be organised on a regional basis. The reason for this guidance was the perception that there was a considerable level of diagnostic inaccuracy and that this could be improved by better integration of the currently available technologies. This is one of a number of major changes in the way that services to patients are being delivered, all of which are centred on the development of multidisciplinary teams responsible for the provision of local services. The introduction of the WHO classification of haematological malignancy provides a structure for the development of integrated haemtopathology laboratories, with its emphasis on definition of disease entities based on clinical, morphological, phenotypical and molecular features. This means that these diagnostic modalities can be used systematically and in parallel to provide effective cross validation of a diagnosis. One of the challenges raised by this approach is the selection of the most informative panels of investigations both at presentation and subsequent follow up from the wide range of options that are now available. The introduction of specialist haematopathology services in the United Kingdom has highlighted a number of scientific and organisational issues that in time may have a wider impact on diagnostic laboratories in general. These include the relationship between size and cost effectiveness and the future role of clinical scientists and medically trained pathologists. Integrated laboratories of the type being developed challenge the prevailing model for delivery of pathological services in the United Kingdom, which is based around the traditional pathology disciplines. These speciality boundaries will become less relevant as long established diagnostic techniques are replaced by the new generation of diagnostic technologies and it is important to establish frameworks of service delivery that can deploy these developments for the benefit of patients.

Flow Cytometry↗

PubMedDate not supplied

Stages of development of the ribosome-lamella complex: an ultrastructural study.

Ribosome-lamella complexes (RLC) are intracytoplasmic organelles observed in a wide variety of disorders, but mostly in hematologic malignancies. Although their close topographic relationship with rough endoplasmic reticulum (RER) suggests their derivation from it, their development and functional role are unclear. Their maturation phases were studied in 20 cases (19 hematologic neoplasms and 1 parathyroid adenoma) where electron microscopy had evidenced their presence. In 19 of thesecases, RLC were in an advanced stage of maturation, whereas in one (acute monoblastic leukemia) they were observed in the early stages of development and appeared to arise from peculiar RER configurations within blast cells, which were rich in both organelles. In this case, the authors observed numerous RER cisternae with distinctive cylindric, concentric and/or whorl configurations, RLC associated and not associated with these configurations, and intermediate structures. The latter were characterized by lamellae devoid of ribosomes oriented parallel to the RER configurations. Reticulum configurations were observed in no other case. The ultrastructural aspects observed in these 20 cases suggest that RLC synthesis proceeds as follows: (1) arrangement of RER in cylindric configurations; (2) synthesis of lamellae oriented parallel to the cylindric configurations (pre-RLC); (3) formation of RLC when ribosomes appear between the lamellae associated with configurations (immature RLC); (4) formation of mature RLC with disappearance of the reticulum.

Blood Platelets↗

PubMedDate not supplied

Pediatric hematology and oncology in Iran.

UNLABELLED: Pediatric hematology and oncology (PHO) is a rapidly expandingfield. It has been our goal to meet the needs and increasing demands for comprehensive medical care of children suffering from chronic blood diseases and malignancies. In the past decade we have been able expand and optimize the PHO services throughout Iran, in general and in respect to their prevalence and clinical importance, by trained pediatric hematologist-oncologists, pediatric surgeons and improved para clinical facilities. Major beta-thalassemics receive blood transfusion and chelation therapy according to the current standards mostly at regional blood banks centers. To curb major beta-thalassemia a premarital screening program has been enacted and abortion has been legitimized if major thalassemia is diagnosed by CVS. Hemophiliacs are supervised and treated as indicated by Iranian Hemophilia Comprehensive Care Centers (IHCCC). Screening for transfusion related complications and transmitted viral diseases (HBV, HCV and HIV) in both cohorts are carried out in regular intervals and necessary management will be then carried out as indicated at respective specialized units. Childhood malignancies are treated according to protocols adopted from accredited institutions in the USA and Europe, with almost comparable results. BMT is available for selected patients with beta-thalassemia or malignancies. By going to public we have been able to rise general awareness about chronic blood diseases and childhood malignancies and have initiated establishment of parents groups and formation of NGOs to support these children and their families. Foundation of Iranian Society of Pediatric Hamatology and Oncology (ISPHO) in the year 2000 has been another step forward to consolidate and coordinate the available manpower and facilities. CONCLUSION: By evaluation of the country's main problems and shortcomings and conduction of collaborative studies and operation planning one will succeed to get the expected feedback and scientifically based approach to provide medical services to far reaching underdeveloped regions.

Cancer Care Facilities↗

PubMed2003

Advances in the treatment of multiple myeloma: the role of thalidomide.

Multiple myeloma (MM) accounts for 1% of all malignancies and 10% of malignant hematological neoplasms. In spite of high-dose therapy with stem cell rescue, relapse and disease resistance are common events in the course of the disease. Thalidomide (Thal) has been successfully used in such situations and it's use has also been expanded to the up-front therapy and as adjuvant to stem cell transplantation. Here, we review the underlying concepts and current clinical data regarding Thal in the treatment of MM.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2002

Sickle cell anemia and hematological neoplasias.

Sickle cell disease (SCD) is a congenital hemolytic anemia with various clinical findings. In some cases hematological neoplasias and some solid tumors may accompany this disease but these have rarely been reported. Here we report five cases with SCD and accompanying hematological neoplasias including lymphoblastic lymphoma, multiple myeloma and hairy cell leukemia in four cases with sickle cell trait and one case of Hodgkin' disease in sickle cell anemia. All of the cases except one had no previously diagnosed congenital hemolytic anemia and/or family history. Peripheral blood findings suggestive for an underlying hemolytic anemia were the first step and the most important initial lead in the detection of SCD. Severe musculoskeletal signs during the first presentation was seen in the lymphoma case, residual renal dysfunction after remission of multiple myeloma, and areas of infarction in the spleen in CT scans in the patient with sickle cell anemia were the most interesting findings in these cases. A standard therapeutic approach without any additional toxicity was relevant in all cases. Detailed clinical presentation and outcome of these five cases are documented here and the literature has been reviewed.

Adolescent↗

PubMed2002

Humoral immunodeficiency in chronic lymphocytic leukemia: role of CD95/CD95L in tumoral damage and escape.

B cell chronic lymphocytic leukemia (B-CLL) is the most frequent hematological neoplasm in the human adult life. This tumor is often associated with hypogammaglobulinemia and infections. This review focuses on recently reported mechanisms underlying the humoral immunodeficiency occurring in B-CLL. Tumoral cells provoke several alterations to normal regulatory T cells, which, in turn, can impair the correct maturation of B cells. In addition, the direct inhibitory effect of B-CLL cells on immunoglobulin (Ig)-secreting plasma cells (PC) may account for the humoral immunodeficiency. This phenomenon is mediated by the interaction of CD95L molecules expressed by B-CLL cells with the death receptor CD95 that is up-regulated on patients' PC, leading to PC apoptosis and subsequently to hypogammaglobulinemia. Furthermore, the presence of CD95L on B-CLL cells could play an additional role in tumoral immune-escape, as reported in other neoplasms.

Agammaglobulinemia↗

PubMed2003

Pharmacological basis for cladribine resistance.

The inherent or acquired resistance of leukemic cells to cytostatic agents is a major clinical challenge. The purpose of this review was to elucidate and analyse the available data concerning mechanisms of resistance of cladribine with emphasis on recent advances in the characterization of activating and inactivating enzymes in the induction of resistance to cladribine. All available in vitro and clinical data on cladribine was undertaken. Cladribine, unlike many other drugs, is toxic to both dividing and indolent lymphoid malignancies. Cladribine is a prodrug and must be phosphorylated intracellularly to cladribine-monophosphate (MP) by the nuclear/cystosol enzyme deoxycytidine kinase (dCK) and the mitochondrial enzyme deoxyguanosine kinase. The cytotoxicity mainly depends on the accumulation of cladribine-triphosphates (TP) after phosphorylation of cladribine-MP by nucleoside monophosphate kinase and nucleoside diphosphate kinase. 5'-Nucleotidase (5'-NT) dephosphorylates cladribine-MP and the accumulation of cladribine-TP depends on the ratio of dCK and 5'-NT in the cells. The mechanisms underlying cladribine resistance are multifactorial, e.g. decreased nucleoside transport, decreased activity or deficiency of dCK, altered intracellular pools of competing nucleotides, altered regulation of ribonucleotide reductase and increased drug inactivation by 5'-NT. Finally, cladribine resistance may be a consequence of a defective induction of apoptosis. In spite of the fact that more than one mechanism can contribute to a cladribine resistance phenotype, a reduction in dCK activity is probably the major determinant of cladribine resistance. Insight into the mechanism of action and resistance to cladribine is crucial for its optimal use as well as for the development of newer analogues.

5'-Nucleotidase↗

PubMed2003

The expression pattern of CD56 (N-CAM) in human bone marrow biopsies infiltrated by acute leukemia.

In hematological neoplasms CD56 (N-CAM) is expressed by T/natural killer (NK) cell lymphoma, by most neoplastic plasma cells in multiple myeloma and also in a subset of acute myelogenous leukemias (AML). In the latter, it is an indicator of poor clinical outcome. Most of the data on CD56 expression in acute leukemia have been obtained by flow cytometric analysis. Up to now, no systematic analysis of the expression pattern of CD56 in formalin fixed paraffin embedded bone marrow biopsies of acute leukemias has been performed. We immunohistochemically studied the expression of CD56 in a series of 141 bone marrow biopsies fixed in Sublimat Mercury II Chloride (SUSA) including 100 cases of AML FAB M0-M7, 11 cases of AML not further specified, 3 cases of biphenotypical leukemia, 20 cases of acute lymphoblastic leukemia (ALL) and 7 cases of reactive bone marrow biopsies. Overall, 14 of 134 (10%) leukemia cases were positive for CD56. Detail analysis revealed positivity in 5/13 cases of AML M5 (38%), 3/9 AML M1 (33%), 1/8 AML M0 (13%), 1/11 AML not specified (9%), 2/31 AML M2 (7%) and 2/26 AML M4 (8%). All cases of ALL and biphenotypic leukemias were CD56 negative. The CD56 expression in AML M5 was statistically significant (p = 0.003). On paraffin embedded bone marrow biopsies CD56 expression occurs in de novo AML with an overall frequency of 13%. It is significantly correlated with AML M5, which is positive in 38% of the cases. Cases of ALL are consistently CD56 negative.

Adult↗

PubMed2006

The risk of tuberculosis in patients with cancer.

Current US guidelines for the management of latent tuberculosis infection in cancer patients are based on studies from 1970s, yet much about cancer care has changed in the interim. In a review of our experience during the past 25 years, we found that incidence of tuberculosis varied significantly according to country of birth and cancer type. Foreign-born patients with underlying hematologic neoplasm had a tuberculosis rate 50-100 times higher than US-born patients, whereas US-born patients with an underlying solid tumor had the same tuberculosis rate as US-born persons without cancer. These findings may help guide the management of latent tuberculosis infection in persons with cancer.

Adolescent↗

PubMed1997

Gating strategy for immunophenotyping of leukemia and lymphoma.

Clinical specimens of blood, bone marrow, lymph node, extranodal tissue, and body fluid were collected from 67 cases of hematologic neoplasms (including chronic lymphoid leukemias, T- and B-cell lymphomas, and acute lymphoblastic and myelogenous leukemias) for comparison between the right-angle light scatter (RALS)/CD45 and the forward-angle light scatter (FALS)/RALS gating combinations. One to three diagnostic markers were selected from each case, yielding 124 paired results for comparison. We found that the percentage of tumor cell isolation and the total cell count in the tumor cell gate were higher in RALS/CD45 than in FALS/RALS. When 20% was used as a cutoff point, 30 markers in FALS/RALS failed to identify the tumor population, while only 3 markers in RALS/CD45 failed to do so. The discriminative factor in the RALS/CD45 gating was mainly the CD45 intensity, whereas all cases except 3 showed low RALS. Although T-cell neoplasms showed a higher proportion of high CD45 intensity, other groups shared similar ranges of CD45 intensity, which is therefore of limited value for differential diagnosis. The RALS/CD45 combination produces higher recovery and purity for tumor cell isolation than the FALS/RALS combination and should replace the latter for routine immunophenotyping of lymphoma and leukemia.

Biomarkers, Tumor↗

PubMed1980

Malignant histiocytosis simulating granulomatous disease.

In its clinical presentation, malignant histiocytosis may mimic infections or hematologic neoplasms, and pathologically it may be mistaken for Hodgkin's disease, histiocytic lymphoma, or viral lymphadenitis. The case histories of three patients in whom malignant histiocytosis clinically and pathologically simulated granulomatous diseases are reported. Erythrophagocytosis was not present in the initial bone marrow aspirates from two of the patients. One patient was considered to hve sarcoidosis or Wegener's granulomatosis; the second patient, Weber-Christian disease, and the third patient, a granulomatous disease of infectious origin. Granulomas have been found in tissues of patients who have Hodgkin's disease, but have been found only rarely in association with malignant histocytosis. An explanation for the presence of granulomas in association with malignant histiocytosis is offered: they may represent a phase in the evolution of the disease.

Adolescent↗

PubMed1984

Practical immunocytochemical identification of human blood cells.

A practical immunocytochemical method of demonstrating surface antigens of human blood cells on air-dried smears or other cytologic preparations has been developed. This method uses monoclonal antibodies as the primary antibodies and calf intestinal alkaline phosphatase as the enzymatic indicator. Combined staining with cytochemical stains for myeloperoxidase or nonspecific esterase on the same slide is also possible when needed. These methods are very useful for accurate identification of human blood cells on the commonly available clinical specimens and are very helpful in the diagnosis and classification of various hematologic neoplasms, including chronic lymphocytic leukemias, acute leukemias, and related diseases.

Antibodies, Monoclonal↗

PubMed2003

EUROCARE-3: survival of cancer patients diagnosed 1990-94--results and commentary.

EUROCARE-3 analysed the survival of 1815584 adult cancer patients diagnosed from 1990 to 1994 in 22 European countries. The results are reported in tables, one per cancer site, coded according to the International Classification of Diseases (ICD)-9 classification. The main findings of the tables are summarised and commented on in this article. For most solid cancers, wide differences in survival between different European populations were found, as also reported by EUROCARE-1 and EUROCARE-2, despite a remarkable (10%) overall increase in cancer survival from 1985 to 1994. Survival was highest in northern Europe (Sweden, Norway, Finland and Iceland), and fairly good in central-southern Europe (France, Switzerland, Austria and Spain). Survival was particularly low in eastern Europe, low in Denmark and the UK, and fairly low in Portugal and Malta. The mix of tumour stage at diagnosis explains much of the survival differences for cancers of the digestive tract, female reproductive system, breast, thyroid, and also skin melanoma. For tumours of the urinary tract and prostate, the differences were explained mainly by differences in diagnostic criteria and procedures. The case mix by anatomic subsite largely explains differences in survival for head and neck cancers. For oesophagus, pancreas, liver and brain cancer, with poor prognoses, survival differences were limited. Tumours, for which highly effective treatments are available, such as testicular cancer, Hodgkin's lymphoma and some haematological malignancies, had fairly uniform survival across Europe. Survival for all tumours combined (an indicator of the overall cancer care performance of a nation's health system) was better in young than old patients, and better in women than men. The affluence of countries influenced overall cancer survival through the availability of adequate diagnostic and treatment procedures, and screening programmes.

Brain Neoplasms↗

PubMed1983

Use of cloned probes to detect Epstein-Barr viral DNA in tissues of patients with neoplastic and lymphoproliferative diseases.

Cloned fragments of the Epstein-Barr virus (EBV) genome were used to examine tissues from 145 patients for the presence of EBV DNA by two techniques: (1) nucleic acid hybridization of cell spots from which the DNA had been extracted in situ and (2) hybridization of DNA that had been transferred to nitrocellulose by Southern blotting. EBV DNA was found in tissues from four adults and five children with American Burkitt's lymphoma, infectious mononucleosis, lymphoma following bone marrow transplant, central nervous system lymphoma, nasopharyngeal carcinoma, and fatal polyclonal B-cell lymphoma following mononucleosis; two patients also had chronic pneumonitis, failure to thrive, and abnormal immune function. Six of the nine patients whose tissues contained EBV DNA had a demonstrable or presumed associated immunologic disorder. EBV DNA was not found in normal tissues or in a variety of hematologic neoplasms and other disorders. Nucleic acid hybridization methods can be used for the routine examination of the association of EBV with lymphomas and other lymphoproliferative syndromes occurring in immunodeficient individuals.

Acquired Immunodeficiency Syndrome↗

PubMed1993

Cancer incidence in a population accidentally exposed to 2,3,7,8-tetrachlorodibenzo-para-dioxin.

In 1976, an accident in a plant near Seveso, Italy, exposed the local population to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Persons residing in three zones of decreasing TCDD contamination (A, B, and R) and a reference population were followed up for cancer occurrence in 1977-1986. The most exposed subgroup (A) was small, and only 14 cancer cases were observed. In zone B, hepatobiliary cancer was elevated, especially for those living in the area for > 5 years [relative risk (RR) = 2.8; 95% confidence interval (CI) = 1.2-6.3]. Men exhibited an increase in hematologic neoplasms, most notably lymphoreticulosarcoma (RR = 5.7; 95% CI = 1.7-19.0). Women experienced an increased incidence of multiple myeloma (RR = 5.3; 95% CI = 1.2-22.6) and myeloid leukemia (RR = 3.7; 95% CI = 0.9-15.7). In zone R, the incidence of soft tissue tumors and non-Hodgkin's lymphomas was elevated, particularly among persons living in the area for > 5 years (RR = 3.5; 95% CI = 1.2-10.4 for sarcomas, and RR = 2.0; 95% CI = 1.2-3.6 for non-Hodgkin's lymphomas). Breast cancer among females was below expectations in the most contaminated zones, and a clear deficit for endometrial cancer was observed in zones B and R.

Adult↗

PubMed2002

STI571 (imatinib mesylate): the tale of a targeted therapy.

STI571 (imatinib mesylate) is an example of the successful development of a targeted agent. Its target is the constitutively active tyrosine kinase (p210bcr-abl) in a hematologic neoplasm, chronic myelogenous leukemia (CML). The results in early clinical trials were remarkable and led to rapid approval by the Food and Drug Administration for clinical use of the STI571 in CML. This article reviews the pre-clinical and clinical development of this agent and also discusses some of the prevailing theories to explain the emerging problem of resistance. Future directions for this drug, possibly directed at other targets, are also discussed.

Animals↗