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PubMed1996

CHOP vs. ProMACE-CytaBOM in the treatment of aggressive non-Hodgkin's lymphomas: long-term results of a multicenter randomized trial.(PETHEMA: Spanish Cooperative Group for the Study of Hematological Malignancies Treatment, Spanish Society of Hematology).

From May 1985 to May 1989, 175 patients with previously untreated aggressive non-Hodgkin's lymphoma were randomized to receive CHOP or ProMACE-CytaBOM. Eligibility criteria included follicular large-cell diffuse small cleaved-cell, diffuse mixed, diffuse large-cell and immunoblastic lymphoma with an Ann Arbor stage II, III or IV. One hundred and forty-eight patients were evaluable. There were no significant differences between the 2 treatments in response rate (83.5% [57.5% CR] for CHOP vs. 88% [62% CR] for ProMACE-CytaBOM), time to treatment failure (29% vs. 31% at 5 yr), or overall survival (42% in both groups at 5 yr). Furthermore, there were no significant differences between the 2 regimens when response rates and outcome were analyzed for different prognostic subgroups. Toxicity was not significantly different between the 2 regimens, although only 1 patient died as result of treatment-related toxicity in the CHOP arm compared to 6 patient in the ProMACE-CytaBOM group (p = 0.126). In conclusion, in this study ProMACE-CytaBOM has not proved to be superior to CHOP in aggressive lymphomas. This trial gives support to the notion that CHOP still is the standard chemotherapy for aggressive lymphomas, and that new treatment approaches for these lymphomas should be compared to CHOP.

Adult↗

PubMed2000

[Significance and features of MLC reaction in histocompatibility determination of donor and recipient in allogenic bone marrow transplantation to patients with hematological malignancies].

AIM: To characterize mixed lymphocyte culture (MLC) reaction used for determination of donor-recipient compatibility before bone marrow transplantation to patients with hematological malignancies and to assess the reaction significance. MATERIAL AND METHODS: The analysis was made of compatibility testing in MLC standard reaction performed in 134 patients with hematological malignancies with HLA-A, -B identical donors-sibs and in 5 patients with haploid identical donors. RESULTS: Out of 134 patients, 22(91%) appeared compatible to donor sibs in MLC reaction, 12(9%) patients were incompatible. Mean RR for MLC-compatible couples made up: in RvD direction 77 +/- 0.17%, DvR 2.61 +/- 0.32%. 93% of RR values ranged from +15 to -15%, the rest--from +25% to -25%. Bone marrow transplantation was made in 83 patients. Graft retention was observed in 77(93%) patients. Acute and chronic graft versus host reaction developed in 15 and 17 patients, respectively. CONCLUSION: An optimal protocol is proposed for examination of compatibility donor-recipient in MLC reaction in patients with hematological malignancies. It is intended for allogenic bone marrow transplantation in hematological departments.

Adolescent↗

PubMed2006

Hematological malignancies in chronic inflammatory bowel diseases: report of five cases and review of the literature.

Several forms of primary and secondary hematological malignancies were rarely observed during the clinical course of inflammatory bowel diseases (IBD). Patients needing a prolonged treatment with immunosuppressants, such as azathioprine or methotrexate, with familiarity and genetic predisposition seem to be at a higher risk of leukemia. On the other hand, asthenia, thickness, and fever may be the symptoms of the onset of each kind of hematological malignancy. The finding of anemia, alteration of leukocyte count and large undetermined cells may suggest increased probability of abnormal proliferation of a single white blood cell line. In this report, the occurrence of hematological malignancies is described in five patients affected by IBD (three with ulcerative colitis and two with Crohn's disease) attending our Gastroenterology Unit.

Adult↗

PubMed2004

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

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

Apoptosis↗

PubMed1996

Phase I-II study of high-dose busulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation for hematological malignancies: toxicities and hematopoietic recovery.

In a phase I-II study, we evaluated toxicities, tolerability, pace of engraftment, and tumor responses to high-dose bulsulfan and cyclophosphamide followed by autologous peripheral blood stem cell transplantation in patients with hematological malignancies. We treated 51 patients with various hematological malignancies involving the bone marrow with busulfan (16 mg/kg) and cyclophosphamide (120 mg/kg) followed by reinfusion of autologous peripheral blood stem cells. Stem cells were previously collected during hematopoietic recovery after cyclophosphamide (100 mg/kg) and etoposide (600 mg/m2) followed by G-CSF (5 micrograms/kg/day). Neutrophil recovery (>0.5 x 10(9)/I) was rapid in the majority of patients (median 10 days after transplant, range 7-91 days), resulting in a low number of days with severe neutropenia (median 7 days, range 5-85 days) and with fever (median 5 days, range 1-13 days). Platelet recovery, however, was delayed in 60% of patients. There was one acute transplant-related death (2%). Four patients died of late, presumed infections, pulmonary complications (interstitial pneumonia). Tumor responses were documented in a significant proportion of these patients with high-risk hematological malignancies. We conclude that peripheral blood stem cell transplantation results in rapid recovery of neutrophils but variable recovery of platelets after high-dose busulfan and cyclophosphamide, when stem cells are harvested following priming with cyclophosphamide/etoposide and G-CSF. The regimen is well-tolerated with limited non-hematological toxicities and transplant-related mortality. While significant tumor responses were documented in this trial, the ultimate efficacy of the regimen needs to be further defined.

Adult↗

PubMed1995

Recombinant interleukin-2 treatment before and after autologous stem cell transplantation in hematologic malignancies: clinical and immunologic effects.

Autologous bone marrow transplantation (ABMT) for hematologic malignancies is associated with a high relapse rate. Interleukin-2 (IL-2) administration is a therapy that may prevent relapse if used when the tumor burden is minimal. In this study we administered recombinant IL-2 (rIL-2) therapy to 12 patients affected by hematologic malignancies either before or after autologous stem cell transplantation (ASCT). rIL-2 was given by a 6 day continuous intravenous infusion with escalating doses, up to 18 x 10(6)/m2/day, depending on patient tolerance. The functional immune responses of the patients were assessed as natural killer (NK) and lymphokine-activated killer (LAK) cytotoxic activities and in vitro interferon-gamma (IFN-gamma) and tumor necrosis factor alpha (TNF-alpha) synthesis. During rIL-2 treatment, the expected side effects occurred; only 3 patients, who showed severe cardiovascular toxicity, required suspension of the treatment. All toxicities reversed after the end of the therapy. Immunologic monitoring was carried out the day before starting rIL-2 infusion and then repeated on days 3, 7, and 14 after rIL-2 was discontinued. Following every rIL-2 course, a pronounced increase in CD3+, CD8+, CD56+ cells was found, with a peak value on day 3. The NK and LAK activities showed a significant increase on day 3 (p < 0.001) over pretherapy values; the increase lasted until day 14, although the difference at later time points was not significant. Before transplant the synthesis of both IFN-gamma and TNF-alpha decreased following rIL-2 therapy, whereas higher levels of these lymphokines were found after posttransplant rIL-2 courses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed2002

Recombinant human soluble tumor necrosis factor (TNF) receptor (p75) fusion protein Enbrel in patients with refractory hematologic malignancies.

PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) is an important effector and regulatory cytokine involved in the pathophysiology of hematologic malignancies, including hairy cell leukemia (HCL), chronic lymphocytic leukemia (CLL), agnogenic myeloid metaplasia (AMM) and Philadelphia-negative myeloproliferative disorders (MPD). We conducted a pilot study to assess the safety of the soluble TNF receptor, etanercept (p75 TNFR:Fc; Enbrel) in patients with refractory hematologic malignancies. METHODS: Patients were eligible if they had refractory HCL, CLL, AMM, or Philadelphia-negative MPD. Enbrel was administered twice weekly at a dose of 25 mg subcutaneously for a minimum of eight doses, and was continued in patients without overt progression. RESULTS: Among the 26 patients enrolled on study, 25 patients were evaluable. Nine patients had AMM, eight CLL, three HCL, and five Philadelphia-negative MPD. Their median age was 60 years (range 30-83 years). A total of 70 courses consisting of 486 doses of Enbrel were administered. Enbrel was well tolerated, without any overt increase in infectious episodes. Stable disease/no objective response was seen in 22 patients (88%) and progression in 3 patients (12%). Three patients with AMM improved (two showed hematologic improvement, and one showed a reduction in liver and spleen size), and two patients (one with CLL and one with Philadelphia-negative MPD) showed improvement in disease-related symptoms. CONCLUSIONS: Enbrel was well tolerated, but no responses were noted in these immunosuppressed patients with refractory hematologic malignancies.

Adult↗

PubMed2004

Intravascular clotting activation and bleeding in patients with hematologic malignancies.

The association between thrombosis, bleeding and neoplastic disease is well recognized. There are distinctive features of the thrombotic and bleeding complications associated with specific hematologic malignancies. A number of procoagulants can initiate intravascular clotting including tissue factor, cancer procoagulant and interleukin-1. The hematologic malignancy most often associated with intravascular clotting and bleeding is acute promyelocytic leukemia. The pathogenesis of the life-threatening bleeding disorder associated with this uncommon subtype of acute myeloid leukemia (AML) is complex and involves disseminated intravascular coagulation, fibrinolysis and proteolysis. Both all-trans retinoic acid and arsenic trioxide result in relatively rapid resolution of the coagulopathy. Intravascular clotting may also be induced by hyperleukocytosis in AML and by the hyperviscosity syndrome observed in multiple myeloma and Waldenström's macroglobulinemia. In the setting of hematologic malignancies, when thromboembolic complications occur, the presence of comorbid thrombophilic conditions should be excluded. Abnormal platelet production and function contribute to the development of thrombosis in patients with myeloproliferative disorders. The Budd-Chiari syndrome may be observed in patients with myeloproliferative disorders. A number of medications have thrombogenic potential, including corticosteroids, thalidomide, L-asparaginase, all-trans retinoic acid and arsenic trioxide.

Anticoagulants↗

PubMed1999

Antifungal prophylaxis with low doses fluconazole in patients with hematological malignancies.

INTRODUCTION: The incidence of mycotic infections in immunocompromised patients has reached a 20-fold rise for the last two decades. AIM: The goal of the study was to evaluate fluconazole efficacy as antifungal prophylaxis in patients with hematological malignancies. MATERIAL AND METHODS: Sixty nine patients with hematological malignancies and neutrophil count less than 1.0 x 10(9)/L received fluconazole orally at a dose of 150 mg every other day. Fluconazole was discontinued when a neutrophil count above 1.5 x 10(9)/L was maintained. Duration of neutropenic periods, afebrile cycles, and incidence of mycotic infections were assessed. The same variables were observed in a control group of 41 patients who did not receive antifungal prophylactic therapy. RESULTS: Both groups were similar in the mean duration of neutropenic period but the afebrile cycles in the patients receiving antifungal prophylaxis were longer by 5 days compared to these in the patients without prophylaxis. The mycotic infections had lower incidence in the patients on antifungal prophylaxis and the difference was statistically significant (p < 0.01). The superficial mycotic infections composed the majority of the clinically and/or microbiologically verified infections. These were presented by oropharyngeal infection (61%), esophageal (22%), and single cases of skin, genital or rectal infections. Candida albicans was isolated in 85% of the cases. The adverse reactions of fluconazole therapy were mild, transient, and easily manageable. No signs of liver and renal dysfunction were observed. CONCLUSION: Lower dose of fluconazole, 150 mg every other day p.o., has the same antifungal effect as a dose of 200 mg/day p.o. in neutropenic patients with hematological malignancies which lowers the cost of treatment.

Adult↗

PubMed1988

Fatal legionellosis in patients with malignant hematologic diseases.

Pneumonia was present in 70/157 (44.6%) autopsied patients with malignant hematologic diseases. In 16/70 patients (22.9%), legionellae were found to be the causative agents by screening lung tissue specimens with the direct fluorescent antibody method. In 5/16 patients with Legionella pneumonia, in whom legionellosis had been suspected clinically, the diagnosis had already been established by serology, urinary Legionella antigen detection, and culture. These results provide evidence that legionellosis is an important pneumonia etiology in patients with malignant hematological diseases. Thus, Legionella diagnostics should be applied routinely, and antibiotics effective in the treatment of legionellosis should be added to the usual therapy in patients with etiologically unexplained pneumonias. In view of the common occurrence of relapses of Legionella pneumonia, antibiotic therapy should be continued for an extended period.

Aged↗

PubMed2006

Immunotoxins in the treatment of hematologic malignancies.

Immunotoxins, composed of protein toxins connected to cell binding ligands including monoclonal antibodies and growth factors, have been developed for several decades to target hematologic malignancies. Protein toxins from either plants or bacteria are extremely potent based on their enzymatic inhibition of protein synthesis and induction of apoptosis. Plant toxins, particularly ricin, are useful for chemically conjugating to monoclonal antibodies, and have shown clinical activity in several types of lymphoma and leukemia. Their dose is generally limited by vascular leak syndrome. Bacterial toxins have been used to produce single chain fusions with either growth factors or recombinant antibody fragments. These agents are smaller in size (55-65 kDa) and exit the bloodstream much more rapidly than the chemical conjugates, and generally do not cause severe vascular leak syndrome. The only approved drug containing a protein toxin is denileukin diftitox, a fusion of human interleukin 2 with truncated diphtheria toxin. Denileukin diftitox has shown efficacy in cutaneous T-cell lymphoma, chronic lymphocytic leukemia, and non-Hodgkin's lymphoma. Recombinant immunotoxin BL22 is an anti-CD22 Fv fragment fused to truncated Pseudomonas exotoxin; it induces complete remissions in a high percentage of patients with chemoresistant hairy cell leukemia. The anti-CD25 recombinant immunotoxin LMB-2 is active in several CD25+ hematologic malignancies. Several other recombinant immunotoxins are undergoing preclinical development for other target antigens expressed on hematologic malignancies.

Animals↗

PubMed2006

Quality-of-life and health benefits of early treatment of mild anemia: a randomized trial of epoetin alfa in patients receiving chemotherapy for hematologic malignancies.

BACKGROUND: Chemotherapy-related anemia is prevalent among patients with hematologic malignancies. A randomized, open-label, multicenter trial of early versus late epoetin alfa in this population was conducted, focusing on quality of life (QOL). METHODS: Patients with non-Hodgkin lymphoma, Hodgkin lymphoma, chronic lymphocytic leukemia, or multiple myeloma and baseline hemoglobin of 10 to 12 g/dL who were scheduled for > or = 4 months of myelosuppressive chemotherapy were randomized to receive < or = 16 weeks of epoetin alfa at a dose of 40,000 U once weekly immediately (early) or to wait and only receive epoetin alfa if hemoglobin decreased to < 9 g/dL (late). Those patients with a hemoglobin level > 12 g/dL after 3 chemotherapy cycles were not randomized. The primary endpoint was a mean change in the Functional Assessment of Cancer Therapy-Anemia (FACT-An) total. RESULTS: In all, 269 patients with a hemoglobin level < or = 12 g/dL were randomized. The mean total FACT-An increased 3.84 (95% confidence interval [95% CI], 0.21-7.46) in early patients and decreased 4.37 (95% CI, -7.99 to -0.74) in late patients (P = .003). Early patients had significantly (P < .05) higher mean scores for total FACT-General; FACT-General physical and functional well-being subscales, total anemia scale, and fatigue subscale; and daily activity, energy, and important activity Linear Analog Scale Assessment scales, as well as reduced bedrest days and restricted activity days. The mean hemoglobin increased 1.2 g/dL (95% CI, 0.98-1.46) in early patients but decreased 0.2 g/dL (95% CI, -0.32-0.12) in late patients (P < .0001). Adverse events were similar between groups (with fatigue being the most prevalent); clinically relevant thromboembolic events were more common in early patients. CONCLUSIONS: Treating mild anemia immediately with epoetin alfa during chemotherapy for hematologic malignancy significantly improved QOL, productivity, and hemoglobin compared with delaying treatment until the hemoglobin level decreases to < 9.0 g/dL.

Adult↗

PubMed1995

Pulmonary fungal infections in patients with hematological malignancies--diagnostic approaches.

In a retrospective study of 56 patients with hematological malignancies and fungal pneumonia we have analyzed the value of different diagnostic procedures. In all patients (Candida n = 29, Aspergillus n = 23, mixed fungal infection n = 4) bronchoscopy and/or high-resolution computed tomography of the lungs was performed. Cultural detection of fungi in bronchoalveolar lavage was successful in 23/32 Candida and 11/23 Aspergillus pneumonias. Other relevant pathogens were identified by bronchoscopy in 21 cases. Thorax CT scans showed diagnostic evidence of fungal pneumonia in 10/13 Candida and in 16/18 Aspergillus infections. Blood cultures were positive in 9/33 Candida pneumonias and in none of aspergillosis cases. Serological testing and surveillance cultures had only limited value for the early diagnosis of pulmonary mycosis. Our data suggest that bronchoscopy and high resolution CT scans are mutually complementary diagnostic tools with high sensitivity in patients with hematological malignancies and new pulmonary infiltrates. These procedures facilitate the early and reliable recognition of invasive fungal disease which may have a bearing on the initiation, length, and differential therapy of antimycotic drugs.

Adolescent↗

PubMed1993

Enterococcal septicemia in patients with hematological malignancies.

Thirty-six cases of enterococcal septicemia in patients with hematological malignancies were reviewed retrospectively and categorized according to their clinical significance using strict previously described definitions. Overall, most of the infected patients were males (77%), had acute leukemia (64%), had recently received cytotoxic drug therapy (86%), were granulocytopenic at the onset of septicemia (77%), and acquired the infection during hospitalization (77%). The source of septicemia was unknown in 18 (50%) patients, intestinal in 15 (42%) and intravascular in three (8%). Mortality was 19% among 21 inpatients who had clinically significant septicemia and 30% among patients with septicemia of uncertain clinical significance. The fatal outcome could be definitively attributed to enterococcal septicemia in only one of the nine inpatients who died. Clinically significant septicemia appeared somewhat more frequently to be polymicrobial (p = 0.06), whereas septicemia of unknown significance presented more frequently as breakthrough septicemia (p = 0.013). Unless associated with intravascular infection, enterococcal septicemia in patients with hematological malignancies seems to represent a marker of cytotoxic drug damage of the intestinal mucosa rather than a truly invasive infection.

Adolescent↗

PubMed2002

Combination assay of urinary free L-fucose and trypsin inhibitor may be useful indicators of disease activity in patients with hematologic malignancies.

L-Fucose is a monosaccharide located at the non-reducing ends of sugar chains of glycoconjugates. Urinary L-fucose (U-FC) is excreted as free L-fucose, and clinically useful as a tumor marker of digestive organ cancers. We evaluated the clinical usefulness of U-FC levels in patients with various hematologic malignancies because U-FC for hematologic malignancies has only rarely been described. The mean U-FC levels in the acute nonlymphocytic leukemia (ANLL), myelodysplastic syndromes (MDS) and myeloproliferative disorders (MPD) groups were significantly higher than in the control group (P < 0.05). Recently, we reported that urinary trypsin inhibitor (UTI) levels in patients with ANLL, MDS, non-Hodgkin's lymphoma and multiple myeloma were significantly elevated, compared with those in healthy adult volunteers. Noninvasive combination assays of UTI and U-FC may have a higher accuracy in diagnosis of ANLL and MDS than those of UTI or U-FC alone. UTI and U-FC combination assays, noninvasive for patients, could be expanded as useful indicators in hematologic malignancies.

Biomarkers↗

PubMedDate not supplied

Central venous catheterization in pediatric patients affected by hematological malignancies.

The objective of this retrospective study was to evaluate the significance and complications of percutaneous central venous catheterization in pediatric patients affected by hematologic malignancies. One hundred and fifty-eight central venous catheters were inserted in 125 pediatric patients (male/female 67/58; median age: 4 years; range 10 m - 6 y.) affected by hematological malignancies. Venous access was obtained by means of a tunnelled silicone rubber Groshong catheter inserted percutaneously in the subclavian vein (91.1%), the internal jugular vein or in the femoral vein. The medial duration of catheterization was 231.8 days (range 8-1014 days). The total number of catheter days was 33,792 (92.6 years). There were no complications related to catheter insertion. Only one patient developed significant post-operative bleeding. One hundred and nine catheters (68.9%) were removed when they were no longer needed and 49 (31.1%) were removed due to complications: 6 catheter occlusions (12.2%), 7 were accidentally withdrawn (14.3%), 3 for local infections (6.1%) and 33 for catheter-related infection (67.3%). A Groshong catheter seems to provide good access to the blood stream for a long period of time with a low incidence of complications in children with acute hematological malignancies.

Acute Disease↗

PubMed1999

Flow cytometric immunophenotyping of bone marrow core biopsies: report of 8 patients with previously undiagnosed hematologic malignancy and failed bone marrow aspiration.

OBJECTIVE: To report a method for flow cytometric immunophenotyping (FCI) bone marrow (BM) core biopsies in patients with hematologic malignancies of the BM who present with a failed BM aspiration ("dry tap"). DESIGN AND SETTING: Core biopsy specimens of BM were obtained from 8 patients who presented with previously undiagnosed hematologic malignancies arising in (7 cases) or secondarily involving (1 case) the BM and a dry tap. Suspensions of the BM core biopsy specimens were prepared and analyzed by FCI methods. DATA EXTRACTION AND DATA SYNTHESIS: The FCI data were analyzed in conjunction with cytomorphologic, histologic, immunohistochemical, and cytogenetic findings in all cases to determine a final diagnosis. CONCLUSIONS: The prepared BM core suspensions were viable and allowed for a complete immunophenotype profile by FCI in all cases, resulting in a clear definition of the cell of origin of the hematologic malignancy. Because of lack of preservation of architectural features and the potential for artifactual alterations of the relative frequency of abnormal cells, the FCI data must always be correlated with histologic sections of the BM biopsy.

Adult↗

PubMed2006

The epidemiology of fungal infections in patients with hematologic malignancies: the SEIFEM-2004 study.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the incidence and outcome of invasive fungal infections (IFI) in patients with hematologic malignancies. DESIGN AND METHODS: This was a retrospective cohort study of patients admitted between 1999 and 2003 to 18 hematology wards in Italy. Each participating center provided information on all patients with newly diagnosed hematologic malignancies admitted during the survery period and on all episodes of IFI experienced by these patients. RESULTS: The cohort was formed of 11,802 patients with hematologic malignacies: acute leukemia (myeloid 3012, lymphoid 1173), chronic leukemia (myeloid 596, lymphoid 1104), lymphoma (Hodgkin's 844, non-Hodgkin's 3457), or multiple myeloma (1616). There were 538 proven or probable IFI (4.6%); 373 (69%) occurred in patients with acute myeloid leukemia. Over half (346/538) were caused by molds (2.9%), in most cases Aspergillus spp. (310/346). The 192 yeast infections (1.6%) included 175 cases of candidemia. Overall and IFI-attributable mortality rates were 2% (209/11802) and 39% (209/538), respectively. The highest IFI-attributable mortality rates were associated with zygomycosis (64%) followed by fusariosis (53%), aspergillosis (42%), and candidemia (33%). INTERPRETATION AND CONCLUSIONS: Patients with hematologic malignancies are currently at higher risk of IFI caused by molds than by yeasts, and the incidence of IFI is highest among patients with acute myeloid leukemia. Aspergillus spp are still the most common pathogens, followed by Candida spp. Other agents are rare. The attributable mortality rate for aspergillosis has dropped from 60-70% to approximately 40%. Candidemia-related mortality remains within the 30-40% range reported in literature although the incidence has decreased.

Candidiasis↗