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PubMed1995

Mucocutaneous paraneoplastic manifestations of hematologic malignancies.

PURPOSE: To review the clinical manifestations, pathophysiology, and oncologic implications of the major mucocutaneous paraneoplastic syndromes that can appear in patients with hematologic malignancies. METHODS: A comprehensive search of the medical literature was conducted. RESULTS: In vesiculobullous conditions, although the primary lesions are blisters, observed abnormalities may include large, flaccid bullae (pemphigus vulgaris), superficial crusted erosions (pemphigus foliaceus), or erythema multiforme-like lesions (paraneoplastic pemphigus). Paraneoplastic neutrophilic dermatoses include Sweet's syndrome and pyoderma gangrenosum. In both of these conditions, the skin lesions are characterized by a dermal infiltrate of mature neutrophils. Vascular dermatoses include vasculitis and erythromelagia. Papulosquamous conditions are characterized by small (papules) or large (plaques) raised skin lesions and are usually associated with solid tumors. Amyloidosis is a malignancy-related condition that probably stems from immune dysregulation. RECOMMENDATIONS: Continued surveillance of patients with potential cutaneous paraneoplastic syndromes is necessary, since the malignancy may not be immediately detectable. Some of the cutaneous paraneoplastic syndromes will respond to specific measures, such as systemic corticosteroid therapy, but for the most part, successful resolution requires eradication of the underlying malignancy.

Hematologic Diseases↗

PubMed2004

Proteomics-based identification of novel Candida albicans antigens for diagnosis of systemic candidiasis in patients with underlying hematological malignancies.

Systemic candidiasis remains a major cause of disease and death, particularly among patients suffering from hematological malignancies. In an attempt to contribute to the discovery of useful biomarkers for its diagnosis and therapeutic monitoring, we embarked on a mapping of Candida albicans immunogenic proteins specifically recognized by antibodies produced during the natural course of systemic Candida infection in this high-risk population. About 85 immunoreactive protein species were detected with systemic candidiasis patients' serum specimens by using immunoproteomics (i.e., two-dimensional electrophoresis followed by Western blotting), and identified through a combination of peptide mass fingerprinting by matrix-assisted laser desorption/ionization-time of flight-mass spectrometry (MALDI-TOF-MS), de novo peptide sequencing using nano-electrospray ionization-ion trap (ESI-IT) MS, and genomic database searches. This proteomic approach has led to the characterization of 42 different housekeeping enzymes as C. albicans antigens. Their biological significance is also discussed. Furthermore, this study is the first to report that 26 of them exhibit antigenic properties in C. albicans, and 35 of them become targets of the human antibody response to systemic candidiasis. Our findings suggest that the production of antibodies to C. albicans phosphoglycerate kinase and alcohol dehydrogenase during systemic candidiasis could be associated with a differentiation of the human immune response. We also highlight the relationship between changes in maintenance of circulating levels of specific anti-Candida antibodies and patients' outcome. Some of these variations, especially the rise of high anti-enolase antibody concentrations, appear to be related to recovery from systemic candidiasis in these patients, which might serve as markers for predicting their outcome. This approach could therefore provide new challenges for diagnosis and clinical follow-up of these fungal infections, and even for antifungal drug or vaccine design.

Adult↗

PubMed1996

The ETV6, CDKN1B and D12S178 loci are involved in a segment commonly deleted in various 12p aberration in different hematological malignancies.

Structural rearrangements including deletions of the short arm of chromosome 12 are frequent cytogenetic findings in various hematologic malignant disorders. Using FISH with a panel of DNA probes we detected loss of a common region of 12p in 22 patients with different hematologic disorders. Nine of them were characterized cytogenetically by a del(12p), seven by unbalanced translocations, and in the remaining cases the loss of the 12p region was masked by translocations and insertions, adding extra material to the short arm of chromosome 12. The smallest commonly deleted region found in all cases analyzed included ETV6, the gene for p27kipl (CDKN1B), and the D12S178 marker.

Adult↗

PubMed1982

VM26 in malignant hematological diseases. A phase II study.

From August 1979 to April 1981, 33 consecutive patients with malignant hematological diseases, entered this phase II study. Sixteen patients had NHL, eight CLL, four Myeloma, three HD, one ALL, and one Polycythaemia vera. Two patients were unevaluable because of early death. The median age was 67 years. Eight patients were not pretreated with drugs. Two CR (5+, 20+ weeks) were obtained among NHL patients, whereas five PR were observed among two NHL, one CLL, one Myeloma, and one HD patients, respectively. Toxicity was almost exclusively hematologic and occurred in ten patients, in one of them causing severe myelosuppression. Moreover, severe asthenia, attributable to VM26, was encountered in three patients, in one requiring the suspension of the treatment.

Drug Evaluation↗

PubMed2006

Frequencies and characterization of cytogenetically unrelated clones in various hematologic malignancies: seven years of experiences in a single institution.

Cytogenetically unrelated clones are uncommon findings in hematologic disorders. In the present study, among the 1,110 various hematologic malignancies analyzed during the past seven years, 27 (2.4%) patients had karyotypically unrelated clones: 3.5% (7/202) of acute myeloid leukemias, 5.3% (11/206) of myelodysplastic syndromes, none of 40 acute lymphoblastic leukemias, 0.4% (1/233) of myeloproliferative disorders, and 2.6% (8/306) lymphoproliferative disorders with clonal chromosomal abnormalities. Twenty-five patients showed two unrelated clones and two had three unrelated clones. The most consistent chromosome abnormalities were del(5q) (seven cases), +8 (six cases), del(20q) (five cases), and del(7q), +12, +21, and -22 (three cases each). Of interest, the high frequency of different numeric or structural abnormalities affecting the same chromosomes in such clones supports the hypothesis that these karyotypically unrelated clones originate from the common malignant clone through submicroscopic molecular genetic changes and evolutionary processes.

Chromosome Aberrations↗

PubMed1986

C-sis and C-abl expression in chronic myelogenous leukemia and other hematologic malignancies.

Cellular oncogenes have been localized at the breakpoints of characteristic chromosomal rearrangements occurring in certain hematologic malignancies. This has been reported to result in aberrant expression of the involved oncogenes. Over 90% of chronic myelogenous leukemia (CML) is characterized by a reciprocal translocation that brings c-abl from chromosome 9 to chromosome 22, and c-sis from chromosome 22 to chromosome 9. To investigate the possible role of these two oncogenes in the leukemic process, we studied their expression in a number of fresh samples obtained from patients with various forms of leukemia, by Northern blot analysis using c-onc probes. Seven of 24 samples obtained from patients with either CML or chronic myelomonocytic leukemia expressed a normal 4.0-kilobase (kb) c-sis transcript. C-sis expression was found only in the accelerated/blast phases but not in the chronic phase of CML. All of the CML Philadelphia chromosome-positive (Ph1+) samples expressed an aberrant 8-kb c-abl transcript. The expression of c-sis in

Humans↗

PubMed1980

Steel needles used for intravenous therapy. Morbidity in patients with hematologic malignancy.

We studied the morbidity associated with steel needles used for intravenous therapy in adults with hematologic malignancy. Of 148 needles, 52 (36.1%) produced local inflammation, increasing with placements exceeding 24 hours, use of dextrose-containing infusate or intravenous antibiotics, granulocytopenia, and local infection. Eight needles (5.4%) caused local infection and three (2.1%) caused septicemia. Of nine bacteremias occurring in the 43 study patients, none of the five caused by Gram-negative bacilli, but three of the four caused by staphylococci, originated from steel needles. Five of eight local infections and all septicemias occurred with placements exceeding 72 hours (P = .016); each patient with septicemia was granulocytopenic. Intravenous steel needles are a major source of morbidity in patients with granulocytopenia or who are otherwise immunologically compromised. The insertion site should be routinely rotated at least every three days. Nosocomial staphlococcal bacteremia in granulocytopenic patients is likely to be due to an intravenous needle or similar device used for vascular access.

Adolescent↗

PubMed1994

[An early phase II study of CPT-11 (irinotecan hydrochloride) in patients with hematological malignancies].

An early phase II study of CPT-11 (irinotecan hydrochloride) was conducted in patients with hematological malignancies by 4 administration regimens in a cooperative study involving 13 institutes in Japan. The overall response rate was 23% (7/30) for non-Hodgkin's lymphoma, 33% (1/3) for Hodgkin's disease, 18% (2/11) for acute lymphoblastic leukemia and 7% (1/15) for acute myelogenous leukemia. One PR was also obtained in a patient with chronic myelogenous leukemia. Among responders, 6 relapsed and refractory malignant lymphomas (ML) and 2 relapsed and refractory acute leukemias (AL) were involved. The response rates in ML with the regimens B (40 mg/m2 for 5 days every 3-4 weeks) and C (40 mg/m2 for 3 days every weeks) were 31% (5/16) and 33% (3/9), respectively. The other regimens (regimen A, 200 mg/m2 once a day every 3-4 weeks and regimen D) resulted in no response. Responses in AL were only observed in regimen D (20 mg/m2 twice a day for 7 days every 3-4 weeks). Major toxicities were leukopenia (91%), nausea/vomiting (74%), diarrhea (73%) and anorexia (64%). The incidence of severe gastrointestinal symptoms was higher in regimen B than regimen C. Further studies are warranted to confirm the effectiveness and safety of CPT-11 against ML and AL. The recommended administration schedule was regimen C for ML and regimen D for AL.

Adolescent↗

PubMed1979

Total body irradiation (T.B.I.). Preliminary results of a new technique in 30 patients with hematologic malignancy.

The authors present the preliminary results of a new technique of total body irradiation (T.B.I.) used in 30 patients with hematological malignancy. The schedule proposed is easy to use and reproducible. The clinical and hematologic tolerance is good even for patients having had previous cyclic polychemotherapy and/or large-field irradiation. Low-grade non-Hodgkin lymphomas previously nontreated appear to be the best indication. Further investigations have to be performed particularly to specify the interest of combining T.B.I. and chemotherapy or T.B.I. and radiotherapy in the treatment of non-Hodgkin lymphomas.

Adult↗

PubMed2000

[Chronic hypereosinophilia and hematologic malignancies].

Peripheral blood and/(or) marrow hypereosinophilia may be associated to various subtypes of myeloid or lymphoid hematological malignancies. Eosinophilia is frequently paraclonal, due to the recruitment of eosinophilic polymorphonuclear cells by cytokines secreted by lymphomatous or leukemic cells. In some myeloid disorders, eosinophilia may also be clonal, due to the involvement of the eosinophilic lineage within the leukemic clone. Generally, hypereosinophilia is only a side-symptom and eosinophilic visceral damages are rare.

Bone Marrow↗

PubMed2004

Inversion of chromosome 12 and lineage promiscuity in hematologic malignancies.

Rearrangements of the short arm of chromosome 12 are among the most common aberrations found in hematologic malignancies, including myelodysplastic syndromes, acute myelocytic leukemias, acute lymphoblastic leukemias, and non-Hodgkin lymphomas. We report on a group of 46 patients with a variety of myelocytic and lymphoid malignancies, all with an inversion of chromosome 12. Both pericentric and paracentric inversions occurred. The identified hotspots for breakage were p13 and q24. These correspond to gene-rich areas of known chromosome instability. The inv(12) is difficult to detect and may be misinterpreted as a partial deletion by routine cytogenetics. Fluorescence in situ hybridization studies revised the G-banding interpretations of a deleted 12p in some cases to an inversion. The inv(12) may occur as the sole abnormality in both myelocytic and lymphoid malignancies, suggesting lineage promiscuity as seen with MLL and ETV6 gene disruptions. The majority of patients with the inv(12) had complex karyotypic changes that predicted a poor prognosis. Of the 24 patients with known clinical follow-up, many were refractory to chemotherapy and overall survival was short.

Adolescent↗

PubMed2006

Report on the second Latin American consensus conference for flow cytometric immunophenotyping of hematological malignancies.

On May 3 and 4, 2005, the Second Latin American Consensus Conference for the Immunophenotyping of Hematological Malignancies took place in Queretaro, México, with representatives from 10 countries of the region and two external consultants. This document summarizes the major conclusions for which consensus were achieved. Major differences regarding the recommendations from the first conference, which took place 9 years ago, concern the medical indications and the antibody panels for immunophenotyping. The aim of disseminating these guidelines to the international community is based on the potential interest for other countries with similar socioeconomic conditions.

Antibodies, Monoclonal↗

PubMed2000

Supportive care in hematologic malignancies: hematopoietic growth factors, infections, transfusion therapy.

A number of recent developments in the supportive care of hematological malignancies have been selected for critical discussion. The first section focuses on the role of evidence-based guidelines in influencing the use of hematopoietic growth factors in medical practice. The next section updates the current clinical status of amifostine (Ethyol, Alza Corp., Palo Alto CA, USA, and US Bioscience, West Conshohocken, PA, USA) the first broad-spectrum cytoprotective agent available. The management of invasive fungal infections and the use of liposomal antifungal agents are reviewed next. Finally, the current status of transfusion support is presented.

Adult↗

PubMed2005

Second allografts for relapsed hematologic malignancies: feasibility of using a different donor.

A second allogeneic hematopoietic stem cell transplant (HSCT) for relapsed hematologic malignancies is an option in select patients after an initial allograft has failed. If the original donor is not available, a different donor may have to be considered. We report our experience of performing a second allogeneic HSCT using a different donor in patients with relapsed leukemia and lymphoma. In a 5-year period, six patients underwent a second allograft with myeloablative conditioning using a different donor. Four of these were retransplanted using a matched-unrelated donor. Four of the patients (67%) remain progression-free at a median follow-up of 32 months (range 3-72). There were no cases of transplant-related mortality. We conclude that a second allogeneic HSCT using a different donor is a viable option for selected patients relapsing after an allograft if the original donor is not available.

Adolescent↗

PubMed1996

Description of primordial germ cells, oogonia, oocytes and embryo-like growth in squash preparations of tissues from hematological malignancies.

This study evidences the presence of primordial germ cells, in tissue squash preparations and sections from hematological malignancies. Primordial germ cells were identified by their morphology, the intense PAS, PAS-D reaction and presence of calcium-activated neutral proteinase. Primordial germ cells gave rise to nuclear vlimata. Immature oogonia exhibited a nuclear envelope and a star-shaped nuclear core, arising from acellular globose bodies impregnated by a nuclear vlima of primordial germ cell. Bone marrow tissue oogonia were PAS and PAS-D positive, identical to fungal ones. Calcium-activated neutral proteinase was demonstrated in the plasma of the acellular globose bodies, the nuclear envelope and the conglomerated primordial germ cells. Immature bone marrow oogonia progressed into mature ones, leptotene, diplotene, dictyotene and mature oocytes. Nuclear vlimata fertilized primordial germ cells, oogonia and oocytes, giving rise to round embryos at the morula and hatching morula-like stages. Embryos consisted of a zonapellucida-like cortex, composed of glycosaminoglycans, glycoproteins, protease and diffuse nuclear material, enclosing developing cells. Primordial germ cells, oogonia and embryos were also demonstrated in squash preparations of adult rat testis and sections of normal rat bone marrow tissues. The observations document that primordial germ cells are the primary stem cells which give rise to nuclear vlimata and oogonia, which constitute the secondary stem germ cells. The results are discussed in terms of stem cell renewal according to the events: primordial germ cells-gametes-fertilization-embryos-primordial germ cells.

Animals↗

PubMed1994

[Bone marrow transplantation from donors other than HLA matched siblings for hematological malignancies. Nagoya Bone Marrow Transplantation Group and Tokai Marrow Donor Bank].

One hundred and fourteen patients with hematological malignancies received bone marrow transplantation from donors other than HLA-identical siblings. Sixty-three patients received transplantations from related donors; 20 were phenotypically identical for HLA-A, B, D/DR (RM0). 32 differed at one locus (RM1) and 11 differed at more than one loci (RM2). Fifty-one transplantations were from unrelated donors; 37 were phenotypically identical and mixed lymphocyte culture (MLC) negative (UR0) and 14 were MLC positive (UR1). One hundred and four patients had durable engraftment. Four (RM1(1), RM2(2), UR0(1)) failed to achieve engraftment. In terms of the probability of > or = Grade II acute graft-versus-host disease (GVHD), there was no significant difference among the groups according to HLA disparity (RM0:25%, UR0:33%, UR1:39%, RM1:47%, and RM2:50%). The probability of chronic GVHD was significantly higher in UR0 and UR1 than RM0 (71%, 75% vs 28%, p < 0.05). The disease-free survival at 3 years was 45% (RM0), 50% (RM1) and 42% (UR0). More than 50% of patients other than RM0 died of fatal complications including GVHD within 60 days after grafting. In conclusion, unrelated donor and related donor mismatched at one locus could be selected for marrow graft in the case of the absence of an HLA-matched related donor. However, more advances in post-transplant management and in histocompatibility testing should be required.

Adolescent↗

PubMed2004

Markers of bacteremia in febrile neutropenic patients with hematological malignancies: procalcitonin and IL-6 are more reliable than C-reactive protein.

Since neutropenic patients with hematological malignancies are at high risk of contracting life-threatening infections, specific markers of infection are needed in cases of febrile neutropenia. The study presented here assessed serum concentrations of C-reactive protein (CRP), procalcitonin (PCT) and interleukin-6 (IL-6) in samples obtained from 31 febrile neutropenic patients. A total of 53 episodes were evaluated, and 18 of these were associated with positive blood culture results. Procalcitonin and IL-6 concentrations differed significantly between bacteremic and non-bacteremic episodes. Procalcitonin values were 0.22 ng/ml [interquartile range (IR), 0.15-1.9] for patients with pneumonia without bacteremia, 0.22 ng/ml (IR, 0.16-0.55) for patients with fever of unknown origin, 0.2 ng/ml (IR, 0.13-0.57) for patients with non-microbial fever and 1.8 ng/ml (IR, 0.35-5.3) for patients with bacteremia. The differences between bacteremic and non-bacteremic episodes had a P-value of 0.003 using the Mann-Whitney test. For IL-6 the median values were 301 pg/ml (IR, 152-1,879) for patients with pneumonia without bacteremia, 207 pg/ml (IR, 94-445) for patients with fever of unknown origin, 177 pg/ml (IR, 142-208) for patients with non-microbial fever and 942 pg/ml (IR, 181-2,807) for patients with bacteremia. Using the Mann-Whitney test, the differences between bacteremic and non-bacteremic episodes were P=0.006. No differences were found in CRP concentrations. Cutoff levels to distinguish between bacteremic and non-bacteremic episodes were chosen using receiver operating characteristic curves: 0.62 ng/ml for PCT and 297 pg/ml for IL-6. Negative predictive values were 84% for PCT and 70% for IL-6. The results indicate that PCT and IL-6 are more reliable markers than CRP for predicting bacteremia in patients with febrile neutropenia.

Adult↗

PubMed1979

Kallikrein system during treatment of hematological malignancies.

Factors of the plasma kallikrein system have been evaluated following the course of 48 patients with hematological malignancies which consisted of 15 cases of AML, 6 cases of myeloproliferative disorders, 14 of lymphoproliferative disorders, 8 of multiple myeloma and 5 of bone marrow carcinomatoses. Normal range of spontaneous activity was 11.4 +/- 3.0 micronM/ml TAMe hydrolyzed, kallikreinogen was 115.8 +/- 26.2 micronM/ml.h and enzyme inhibitor was 1.02 +/- 0.37 unit. Lower kallikreinogen level of the range was from 77.2 to 93.1; higher spontaneous activity, 8.4 to 18.0 and lower enzyme inhibitor activity of 0.46 to 0.92 was seen before treatment. Kallikreinogen increased up to the range of 95.6 to 120.1 at complete remission and decreased down to 63.1 - 76.5 prior to death. The causes of the change in these factors were discussed.

Adult↗