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PubMed1994

[Enterococcus faecium obtained from surveillance cultures of the stool of the patients with hematological malignancies].

Surveillance cultures of the stool were obtained from 55 patients with hematological malignancies, who have been receiving norfloxacin or tosufloxacin during their neutropenic periods, from May, 1991 to September, 1992. Cultures were performed using 5% blood agar with piperacillin 300 micrograms/ml and amikacin 20 micrograms/ml and bacteria resistant to these antibiotics were analyzed further. Thirty-four over 55 patients were positive for enterococci and 22 strains of 23 examined were Enterococcus faecium. They are resistant to quinolones, aminoglycosides, cephalosporins and penicillins but not to vancomycin. Eighteen of them were also resistant to high-dose gentamicin. Appropriate measures should be used to prevent intrahospital spread of these resistant isolates.

4-Quinolones↗

PubMed1977

Pulmonary alveolar proteinosis: its association with hematologic malignancy and lymphoma.

Pulmonary alveolar proteinosis (PAP) developed in 5 patients with hematologic malignancy or lymphoma. Possible pathogenetic mechanisms which might predispose the patient to this association include the unavailability of competent alveolar phagocytes secondary to profound leukopenia, or inhibition of alveolar phagocytosis by elevated globulins. The spectrum of pulmonary abnormalities produced by PAP includes classical butterfly perihilar alveolar consolidation, lobar consolidation, parenchymal nodules, and hilar adenopathy. Four of the 5 cases had complicating infections, making the exact radiological correlation with PAP difficult.

Adolescent↗

PubMed1994

Changing etiology of bacteremia in patients with hematological malignancies in Denmark.

To ascertain whether the microbiological etiology of bacteremia among patients with hematological malignancies has changed in Denmark, the species distribution of clinically relevant blood culture isolates from the Hematological Department at Rigshospitalet, Copenhagen in 1990 was compared with 2 previous studies (1970-72; 1981-85). In addition, time trends of the etiology of bacteremia among hematological patients in Copenhagen (eastern Denmark) and in Arhus (western Denmark) were compared. In contrast to many other studies, a significant increase in the proportion of Gram-negative aerobes was observed in Copenhagen (from 43% in 1981-85 to 55% in 1990; p < 0.05), whereas in Arhus the proportion of Gram-positive aerobes increased steadily during the 1980s (from 34% to 51%; p < 0.05). In Copenhagen, non-hemolytic streptococci and Xanthomonas maltophilia increased significantly and accounted for 10% (p < 0.01) and 5% (p < 0.05) respectively, of all isolates in 1990, whereas Staphylococcus aureus during the 2 decades studied decreased from 25% to 8% (p < 0.001). In both regions, a decrease was observed in the proportion of Pseudomonas aeruginosa which accounted for only about 5% of all isolates in 1990. No changes were observed in the rates of anaerobes and yeasts. Several factors may contribute to the reported differences in the etiology of bacteremia among hematological patients, e.g. criteria used to assign the clinical significance of the isolate, blood culture system used, practice of using indwelling intravenous catheters, different policies with respect to antimicrobial treatment, and the degree of immunosuppression. A local surveillance of blood culture isolates is mandatory if changes in etiology and resistance development are to be detected.

Bacteremia↗

PubMed2001

[Allogeneic hematopoietic stem-cell transplantation for hematological malignancies].

Allogeneic transplantation of hematopoietic stem cells (HSC) is a curative treatment for hematological malignancies aiming to eradicate the malignant clone using the immunological conflict inherent to donor HSC installation in the recipient. The different possible sources of HSCs (bone marrow, blood, and cord blood) and better knowledge of HLA typing has led to the development of new transplantation techniques and modalities (transplantations after non-myeloablative conditioning, haploidentical transplantations, etc.), which should improve patient survival and extend allograft indications. HSC allografting is subject to immunological reactions stemming from the histocompatibility discrepancy between donor and recipient. For the most part, these are reactions of the graft against the host (graft-versus-host disease: GVHD) and graft rejection (host-versus-graft: HVG). This immunological conflict can also be responsible for recognizing and destroying the recipient's residual tumor cells, which carry specific tumor antigens and/or minor antigens of histocompatibility (graft-versus-leukemia effect, GVL or graft-versus-malignancy effect, GVM). The posttransplantation period can also be riddled with various complications such as veno-occlusive disease, endocrine complications, as well as complications arising from infections and secondary neoplasms because of a more or less substantial and durable immune deficiency. Acute and chronic leukemias are the major indications for HSC allogeneic transplantation, for which the results are variable and closely related to the patient status, the hematological disease, and the transplant procedure. Other hematological diseases are also indications for allogeneic transplantation but are rarer, for which allogeneic transplantation remains nevertheless the only curative treatment, despite an overly high level of toxicity. Improvement in the results of unrelated transplantations, use of peripheral HSC or cord blood cells, development of non-myeloablative conditioning regimens, and techniques of ex vivo manipulation of the graft have allowed HSC allogeneic transplantation indications to be extended. The antitumor efficacy of donor lymphocytes infusion for relapses after transplantation mirrors the GVL effect and is the first stage in a targeted cellular immunotherapy using sensitized lymphocytes or dendritic cells.

Bone Marrow Transplantation↗

PubMed1998

Achromobacter xylosoxidans bacteremia in patients with hematologic malignancies.

We report nine cases of Achromobacter xylosoxidans bacteremia diagnosed in patients with hematologic malignancies. There was not an obvious epidemiologic link between cases and the organism was not isolated from any source. Outcome was cure in all nine cases. In our experience, catheter removal is generally required for eradication of A. xylosoxidans.

Adult↗

PubMed2006

Evolving role of radiation therapy for hematologic malignancies.

Radiation therapy continues to play a paramount role in the therapy of hematologic malignancies, whether as definitive therapy, as consolidation after chemotherapy, as part of bone marrow transplantation protocols, or in palliation. During the past 2 decades, significant advances in radiation therapy have occurred, including the evolution of involved-field irradiation and the adoption of conformal radiation administration. It is hoped that modern techniques will reduce the long-term sequelae associated with radiation-based treatments.

Hematologic Neoplasms↗

PubMed1986

Alpha interferon in the treatment of hematologic malignancies.

The interferons are an important first member of a family of biologic response-modifiers used in treating human malignancies. Activities associated with the interferons include inhibition of viral replication, influence on cellular protein production, direct antiproliferative effects, and a variety of modulatory effects on the immune response. These regulatory functions of interferon underlie the interest in its use as an anticancer agent. Alpha interferon is the most extensively studied interferon species. Although antitumor activity has been seen both in vitro and in vivo in some solid malignancies, the most impressive responses have occurred in the hematologic malignancies. More than 90 percent of patients with hairy cell leukemia have a sustained recovery of their peripheral blood cell counts with alpha interferon therapy. Approximately 50 percent of patients with low-grade non-Hodgkin's lymphoma and cutaneous T cell lymphoma demonstrate a response to alpha interferon. More than 80 percent of patients with chronic myelogenous leukemia have a response to alpha interferon, and in one study, nearly half of the patients with response had complete suppression of the Philadelphia chromosome clone on at least one examination. Ongoing clinical trials are addressing such issues as optimal dosage, duration of alpha interferon therapy, and combinations of alpha interferon with other biologic agents, chemotherapy drugs, and radiation.

Humans↗

PubMed2005

A randomized, double blind comparative study of prophylactic parenteral nutritional support with or without glutamine in autologous stem cell transplantation for hematological malignancies -- three years' follow-up.

Forty-four adult autologous transplant patients with hematological malignancies were randomized to receive either prophylactic parenteral nutrition PN (P group), or PN given ad hoc (C group). In each group, they were further randomized to receive standard PN (B group), or PN with 0.5 g glutamine/kg as L-Ala-L-Gln (A group). The overall survival (OS), disease-free survival (DFS) and event-free survival (EFS) in groups C vs. P and A vs. B were compared during follow-up with median 38 months. The final outcome rates in C/P/A/B groups, respectively (OS 65/81/63/85%, EFS 45/53/33/65% and DFS 56/50/35/77%), were not significantly different, apart from A < B in DFS rate (p=0.03, Fisher's exact test). Also in survival analysis (logrank test), no significant difference between groups C and P was found but generally worse parameters were observed for A vs. B group: for DFS (p=0.04) and EFS (p=0.01) the difference was significant, and for OS (p=0.09) it was borderline. In the three years' follow-up, no clinically useful benefit of prophylactic PN in autologous transplant patients was proven. Also, glutamine supplementation was not helpful, and was even connected with apparently worse long-term outcome.

Adolescent↗

PubMed1998

Veno-occlusive disease of the liver after allogeneic bone marrow transplantation in children with hematologic malignancies: incidence, onset time and risk factors.

One hundred and forty children with hematologic malignancies undergoing allogeneic BMT were reviewed in order to clarify the incidence, onset time, and risk factors for veno-occlusive disease (VOD) of the liver. Thirty-eight patients (27.1%) developed VOD diagnosed according to the Seattle clinical criteria. Seventeen patients developed VOD within 20 days of transplantation (early-onset) and in 21 patients developed after day 20 (late-onset) including eight patients with histological confirmation. Late-onset VOD occurred from day 21 to day 508 (median day 39). Moderate or severe VOD developed in 11 early-onset and 13 late-onset patients. Death occurred in eight early-onset and 10 late-onset patients. Serum albumin and cholinesterase levels prior to the start of pretransplant conditioning were significantly lower in early-onset VOD than in late-onset VOD. Multivariate analysis showed that low serum albumin levels (< or =3.7 g/dl) prior to the start of pretransplant conditioning was most strongly associated with the development of VOD. Donor mismatch (other than HLA-matched relatives), use of minocycline, and a long interval (> or =13 months) between diagnosis and BMT were also significantly associated with the development of VOD. In contrast, use of fosfomycin was associated with a decreased risk. Our data suggest that hepatic function reserve is important in the development and onset time of VOD. Veno-occlusive disease of the liver is a complication which may occur a long time after transplantation.

Adolescent↗

PubMed2005

Population pharmacokinetic analysis of vancomycin in patients with hematological malignancies.

This study determines vancomycin (VAN) population pharmacokinetics (PK) in adult patients with hematological malignancies. VAN serum concentration data (n = 1,004) from therapeutic drug monitoring were collected retrospectively from 215 patients. A one-compartment PK model was selected. VAN pharmacokinetics population parameters were generated using the NONMEM program. A graphic approach and stepwise generalized additive modeling were used to elucidate the preliminary relationships between PK parameters and clinical covariates analyzed. Covariate selection revealed that total body weight (TBW) affected V, whereas renal function, estimated by creatinine clearance, and a diagnosis of acute myeloblastic leukemia (AML) influenced VAN clearance. We propose one general and two AML-specific models. The former was defined by CL (liters/h) = 1.08 x CL(CR(Cockcroft and Gault)) (liters/h); CV(CL) = 28.16% and V (liters) = 0.98 x TBW; CV(V) =37.15%. AML models confirmed this structure but with a higher clearance coefficient (1.17). The a priori performance of the models was evaluated in another 59 patients, and clinical suitability was confirmed. The models were fairly accurate, with more than 33% of the measured concentrations being within +/-20% of the predicted value. This therapeutic precision is twofold higher than that of a non-customized population model (16.1%). The corresponding standardized prediction errors included zero and a standard deviation close to unity. The models could be used to estimate appropriate VAN dosage guidelines, which are not clearly defined for this high-risk population. Their simple structure should allow easy implementation in clinical software and application in dosage individualization using the Bayesian approach.

Adult↗

PubMed2002

Reduced-intensity conditioning followed by allografting of hematopoietic cells can produce clinical and molecular remissions in patients with poor-risk hematologic malignancies.

A reduced-intensity conditioning regimen was investigated in 45 patients with hematologic malignancies who were considered poor candidates for conventional myeloablative regimens. Median patient age was 49 years. Twenty-six patients previously failed autologous transplantation, and 18 patients had a refractory disease at the time of transplantation. In order to decrease nonrelapse mortality, and enhance the graft-versus-tumor effect, a program was designed in which a reduced conditioning with thiotepa, fludarabine, and cyclophosphamide was associated with programmed reinfusions of donor lymphocytes for patients without graft-versus-host disease (GVHD), not achieving clinical and molecular remission after transplantation. GVHD prophylaxis consisted of cyclosporine A and methotrexate. Seventeen patients received marrow cells and 28 received mobilized hematopoietic cells. All patients engrafted. The probability of grades II-IV and III-IV acute GVHD were 47% and 13%, respectively. The probability of nonrelapse mortality, progression-free survival, and overall survival were 13%, 57%, and 53%, respectively. Thirteen patients in complete remission had a polymerase chain reaction marker for minimal disease monitoring; 10 achieved molecular remission after transplantation. Nine patients received donor lymphocytes: one patient with mantle cell lymphoma had a minimal response, one patient with refractory anemia with excess of blasts in transformation achieved complete remission, and 7 patients did not respond. At a median follow-up of 385 days (range, 24 to 820 days), 25 patients (55%) were alive in complete remission. Although longer follow-up is needed to evaluate the long-term outcome, the study shows that this regimen is associated with a durable engraftment, has a low nonrelapse mortality rate, and can induce clinical and molecular remissions.

Adult↗

PubMed1992

Emphysematous cystitis due to Clostridium perfringens and Candida albicans in two patients with hematologic malignant conditions.

BACKGROUND: Fever, abdominal pain, and hematuria developed in two patients with hematologic malignant conditions (multiple myeloma and agnogenic myeloid metaplasia). Each patient was found to have emphysematous cystitis (EC), secondary to Clostridium perfringens and Candida albicans, respectively. Both patients had debilitated general medical conditions, compromised immune function, prior treatment with broad-spectrum antibiotics and corticosteroids, bladder outlet obstruction, and indwelling Foley catheters as predisposing factors to EC. Neither was diabetic. METHODS: These cases provide an opportunity to review the related medical literature on the pathophysiology and management of this uncommon entity. RESULTS: Treatment consists of control of underlying diabetes (if present), administration of appropriate antibiotics, establishment of urinary drainage, provision of supportive general medical care, exclusion of the presence of a bladder fistula, and surgical debridement only when unavoidable. CONCLUSIONS: EC should be part of the differential diagnosis in patients with cancer who have fever, abdominal pain, and hematuria.

Aged↗

PubMed1999

[Measurement of soluble Fas in patients with hematological malignancy].

We measured serum levels of soluble Fas(sFas) in 68 patients with hematological malignancy by using sandwich ELISA and detected bone marrow mononuclear cell membrane Fas(mFas) positive cells in 46 patients with acute leukemias by immunohistochemical technic. It was found that sFas levels were significantly higher in acute lymphoblastic leukemia(ALL) patients(median 10.48 +/- 5.89 ng.ml-1) and non-Hodgkin's lymphoma(NHL) patients(median 18.26 +/- 16.47 ng.ml-1) than those in healthy donors (median 0.92 +/- 0.88 ng.ml-1) (P < 0.05). Elevated sFas levels were correlated with the disease stage and progress, but not with other clinical parameters. According to the follow-up of five ALL patients, their serum sFas levels decreased after complete remissions. We conclude that sFas has prognostic value and is an effective clinical parameter with ALL or NHL patients. In addition, sFas levels in the sera of acute non-lymphoblastic leukemia patients were also found to be unchanged compared with those in the normal control.

Adolescent↗

PubMed1992

[Immune gene rearrangement as markers of hematological malignancies].

Molecular genetical analysis using Ig and TCR genes has been applied for hematological malignancies. In acute leukemias, this method is used to clarify the cellular lineage, and in malignant lymphomas to detect the monoclonal component. In this article, we describe the mechanism of immune gene rearrangement and the present status and future directions of immunogenetic analysis of leukemias and lymphomas.

Gene Rearrangement, T-Lymphocyte↗

PubMed1987

Chromosome abnormalities involving band 13q14 in hematologic malignancies.

Fifteen patients with hematologic disorders showed abnormalities involving chromosome band 13q14. Nine patients had an interstitial deletion of this band, similar to that reported in some retinoblastoma tumors and as a constitutional abnormality in a small proportion of cases of familial retinoblastoma. In five patients, band 13q14 was involved in translocations and in one case there was a deletion of one chromosome #13 and a translocation involving the homologous #13. The diagnosis in the majority of our patients (11 of 15) was chronic lymphocytic leukemia. In these patients the abnormalities were detected in cultures stimulated with 4-phorbol 12-myristate 13-acetate (PMA). It is possible that the utilization of this agent is a fundamental requirement for the reliable demonstration of abnormalities involving 13q14 in patients with B-cell malignancies. The incidence of abnormalities involving 13q14 and their significance in the development of neoplasias, other than retino-blastoma, is discussed.

B-Lymphocytes↗

PubMed2005

Caspofungin as first line therapy of pulmonary invasive fungal infections in 32 immunocompromised patients with hematologic malignancies.

Invasive Fungal Infections (IFI) remain a severe and major complication among patients with hematologic diseases, but the recent availability of new antifungal agents (echinocandins and new azoles) have improved the chance of cure. Caspofungin (Cancidas-Merck) is a large lipopeptide molecule able to inhibit the enzyme complex 1,3-d-glucan synthetase; this action specifically damages the fungal cell wall. Caspofungin (CAS) is active, in vitro and in vivo, against most Candida species and Aspergillus species. We report on our experience with this drug as first-line therapy for proven or probable pulmonary IFI in immunocompromised patients with hematologic malignancies. Thirty-two consecutive patients (20 males and 12 females, with a median age of 52 yr) have been treated with CAS (27 acute leukemias, 1 chronic leukemia, 3 lymphomas and 1 multiple myeloma). Sixteen patients (50%) had a relapsed or resistant hematologic disease, while 12 patients were in complete remission and 4 were at onset of disease; 8/32 (25%) developed IFI after a hematopoietic stem cell transplant (HSCT) procedure. Seven out of 32 patients (22%) had a proven pulmonary IFI (7/7 Aspergillosis) and 25 (78%) had a probable IFI with pulmonary localization as defined according to international consensus. Thirty-one patients (97%) had less than 1000 granulocytes/mL at onset of infection and at the start of CAS therapy. The CAS was given at the dose of 70 mg on day 1, followed by 50 mg/day. Median duration of CAS therapy was 20 d (range 8-64); all the 31 neutropenic patients received concomitant granulocyte colony-stimulating factor (G-CSF). The overall response rate was 56% (18/32) with 12/18 complete responses and 6/18 partial responses; two patients (6%) had a stable disease. Twelve out of 32 (38%) did not respond and seven died of mycotic infection. Univariate analysis showed that granulocytes recovery (>500/mL vs. <500/mL) and status of hematologic disease (remission/onset vs. refractory/relapsed) were significantly associated to favourable outcome. No clinical adverse events (AE) were reported and only a grades I and II transient increase of serum alkaline phosphatase and/or transaminases occurred in 4/32 (12%) patients. After CAS therapy six non-responders and six cases with a partial or stable response were rescued with voriconazole. Two out of six patients (33%) in the former group and 6/6 (100%) in the latter obtained a complete resolution of IFI. Our experience suggests an efficacy of CAS, in combination with G-CSF, as first-line treatment of proven or probable IFI with pulmonary localization. The drug was well tolerated and there were no significant hepatic AE even in patients receiving CAS with cyclosporine after a HSCT. A significant proportion of non-responders or partial responders to CAS can be rescued with a subsequent voriconazole-based therapy.

Adult↗

PubMed1990

[Clinical evaluation of imipenem/cilastatin sodium in infectious complications of hematological malignancies. Tohkai Research Group on Infections in Hematological Disorders].

Imipenem/cilastatin sodium (IPM/CS), a newly developed carbapenem antibiotic, was administered to a total of 152 patients with severe infections complicating hematological disorders, of whom 138 patients are included in the present analysis of efficacy and 152 in that of safety. Most of the underlying diseases were acute leukemia (76/138), and most patients suffered from sepsis or suspicion of sepsis (84/138). Out of 138 patients in whom efficacy was evaluable, responses were excellent in 41 patients, good in 55, fair in 19, and poor in 23. The overall clinical efficacy rate was 69.6% (96/138). Prior antibiotic treatment and peripheral neutrophil count had significant effects on the clinical response. The overall eradication rate of bacteria was 76.2%. Adverse reactions were observed in 15 patients (9.9%) and abnormal laboratory test results in 19 patients (12.5%). From the above findings, IPM/CS is considered to be a useful antibiotic for the treatment of severe infections accompanying hematopoietic disorders.

Adolescent↗

PubMed2006

Comparative single-institute analysis of cord blood transplantation from unrelated donors with bone marrow or peripheral blood stem-cell transplants from related donors in adult patients with hematologic malignancies after myeloablative conditioning regimen.

We studied the clinical outcomes of 171 adults with hematologic malignancies who received unrelated cord blood transplantation (CBT) as a primary unrelated stem-cell source (n=100), or bone marrow transplant (BMT) or peripheral blood stem-cell transplant (PBSCT) from related donors (n=71, 55 BMT and 16 PBSCT). All patients received myeloablative regimens including 12 Gy total body irradiation. We analyzed the hematologic recovery, and risks of graft-versus-host disease (GVHD), transplantation-related mortality (TRM) and relapse, and disease-free survival (DFS) using Cox proportional hazards models. Significant delays in engraftment occurred after cord blood transplantation; however, overall engraftment rates were almost the same for both grafts. The cumulative incidences of grades III to IV acute and extensive-type chronic GVHDs among CBT recipients were significantly lower than those among BMT/PBSCT recipients. Multivariate analysis demonstrated no apparent differences in TRM (9% in CBT and 13% in BMT/PBSCT recipients), relapse (17% in CBT and 26% in BMT/PBSCT recipients), and DFS (70% in CBT and 60% in BMT/PBSCT recipients) between both groups. These data suggest that unrelated cord blood could be as safe and effective a stem-cell source as related bone marrow or mobilized peripheral blood for adult patients when it is used as a primary unrelated stem-cell source.

Adolescent↗