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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autologous bone marrow transplantation (ABMT) is an increasingly effective treatment option for both hematologic malignancies and solid tumors. The dose-limiting toxicity of bone marrow suppression after intensive chemotherapy and/or radiation therapy can be minimized by reinfusing the patient's stored marrow. However, the ABMT procedure involves a period of profound neutropenia before the reinfused marrow engrafts and it also carries a significant risk of major organ toxicities. Common adverse effects of the procedure include mucositis, pneumonitis, renal failure, and veno-occlusive disease of the liver. In this article, Orem's Self-Care Model is used as a framework for assessing ABMT patients with the goal of recognizing developing complications early.
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PMID:Assessment of the autologous bone marrow transplant patient according to Orem's self care model. 147 87

The purpose of this trial was to evaluate the efficacy and the tolerance of high-dose therapy with autologous stem cell transplantation as part of front-line therapy in Hodgkin's disease for patients with both adverse prognostic factors: high tumor burden at presentation and slow response to initial chemotherapy. In a prospective one-center study, 20 consecutive patients with slow response (tumor reduction < 75%) (16 pts) or refractory (4 pts) to 3-4 courses of conventional HD chemotherapy received high-dose therapy followed with autologous bone marrow (14 pts) or peripheral blood stem cell (6 pts) transplantation. They were 13 males, 7 females, median age 26 years (8-45). At the time of initial diagnosis, all but one of the patients had B symptoms, all had high-risk HD defined as Ann Arbor stage IV (7 pts) or large mediastinal involvement (LMI = tumor/thorax > 0.45 at T5-T6) (6 pts) or both stage IV+LMI (7 pts). Median time between diagnosis and autotransplantation was 5 months. Intensive therapy consisted of either CBV (cyclophosphamide 1.5 g/m2 x 4, BCNU 300 mg/m2, etoposide 200 mg/m2 x 3) (12 pts) or cyclophosphamide 120 mg/kg + 12 Gy total body irradiation for 8 patients with diffuse bone or lung involvement. For pts treated with CBV, 40 Gy involved field radio-therapy was performed after hematological recovery. Median duration of neutropenia was 16 days (9-21). Neither veno-occlusive disease, nor interstitial pneumonitis nor toxic death were observed. Seventeen pts are alive with no progression of the disease (16/16 in partial response after initial chemotherapy, 1/4 with refractory disease).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Early intensive therapy with autotransplantation for high-risk Hodgkin's disease. 751 54

An increasing number of volunteer unrelated donor bone marrow transplantations (VUD-BMT) are performed every year for hematological malignancies due to the availability of a large donor pool. Here we show the results of 36 VUD transplants from our institution using a chemotherapy-only conditioning regimen comprising busulfan 4 x 4 mg/kg and cyclophosphamide 2 x 60 mg/kg. All patients received heparin 200 IU/kg bw continuous i.v. infusion starting the day before conditioning until day +30. Thirty-four of 36 patients (94%) engrafted and no secondary graft failure was observed. The two non-engraftments occurred in patients with CML in blast crisis with extensive myelofibrosis. All 34 engrafted patients (100%) were in complete remission on day +30 as shown by bone marrow biopsy and cytogenetic examinations. No life-threatening treatment-related morbidity or mortality (TRM) were observed, in particular, no severe veno-occlusive disease (VOD) of the liver and no fatal pulmonary complication. Use of G-CSF significantly shortened the time of neutropenia by 5 days. GVHD prophylaxis consisted of CsA/methylprednisolone with or without MTX. Acute GVHD grade II-IV was observed in 18/34 patients (53%) and cGVHD in 12/27 patients (45%), who survived to day +100. In seven patients (four with HLA class I or II mismatch) anti-T-lymphocyte globulin (ATG) was added for acute GVHD prophylaxis. One of seven had aGVHD grade II and none developed grade III to IV GVHD or graft failure. We conclude that Bu/CY is a feasible, save and sufficiently immunosuppressive regimen for VUD transplantation. Severe acute GVHD might be avoided by additional use of ATG in GVHD prophylaxis.
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PMID:Busulfan/cyclophosphamide in volunteer unrelated donor (VUD) BMT: excellent feasibility and low incidence of treatment-related toxicity. 920 9

We monitored 30 laboratory hemostatic parameters in an attempt to better comprehend alterations in coagulation and fibrinolysis in 10 patients with hematological malignancies subjected to autologous peripheral blood stem cell transplantation (APBSCT). These parameters were assessed before and just after high-dose conditioning chemotherapy, on days 1, 7, 14 and 28. Although, clinical manifestations associated with fibrino-coagulation disorders never occurred, including veno-occlusive disease, a statistically significant increase was seen in 7 of 30 parameters, compared to values seen before conditioning chemotherapy. These were subdivided into early and late phase parameters. The early phase parameters, which increased during the first day after the conditioning chemotherapy was given, then returned to baseline values, included protein C, plasma tissue factor and tissue-plasminogen activator. The late phase parameters, which increased over baseline values during days 7 to 28, included free-protein S, fibrinogen, plasmin-alpha2-plasmin inhibitor complex and soluble-thrombomodulin. The increase of early phase parameters, as produced by the liver and by endothelial cells, may reflect tissue damage by conditioning chemotherapy. Late phase parameters increased in parallel with C-reactive protein, which suggests a correlation with the degree of inflammation, such as the presence of infective disease during neutropenia. These subclinical alterations in coagulation and fibrinolysis which take on a biphasic pattern during the course of APBSCT should be kept in mind by the attending physicians during therapy.
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PMID:Subclinical alterations in coagulation and fibrinolysis in patients undergoing autologous peripheral blood stem cell transplantation. 951 13

Pretransplant conditioning therapy with i.v. BuCy followed by allogeneic hematopoietic stem cell transplantation (BMT) was investigated in a phase II trial in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). We gave i.v. Bu at a dose of 0.8 mg/kg every 6h x 16 doses, followed by Cy 60 mg/kg daily for 2 days. Twenty-six AML patients (18 males/eight females) were treated, only eight of whom were in CR1. The rest were either refractory to induction chemotherapy (four patients) or in a more advanced stage of their disease (14 patients). In addition, nine patients with MDS (1M/8F) were treated. Their median age was 41 years (range 21-64). Engraftment to > or =500 neutrophils/microl was reached at 14 days (range 10-29 days) post BMT, and the median time of neutropenia was only 11 days (range 4-28 days). The most common regimen-related toxicity was grade 2-3 nausea. In the post-BMT period (including BMT day +30), two patients died, one each from pulmonary hemorrhage secondary to CMV pneumonia and hepatic veno-occlusive disease (VOD), for an early treatment-related mortality (TRM) of 5.7%. Three patients developed VOD and two of them died. There was no direct regimen-related pulmonary or neurologic toxicity. Overall, the clinical side-effect spectrum was analogous to what would be expected from a high-dose oral Bu-based regimen; there was no unique toxicity experienced with the used solvent system. The disease-free survival in the high-risk subgroup (all patients not in CR1) at 1 and 2 years post transplant was 44% and 31%, respectively. The 13 patients still alive in CR have been followed for a median of 24 months (range 18-32). Pharmacokinetic analysis showed very good interdose reproducibility, and limited interpatient variability in area under the plasma concentration vs time curve, peak concentration, and clearance of Bu after this i.v. formulation. We conclude, that this new i.v. Bu formulation is well tolerated; it has an impressive safety profile, and we suggest that it should be considered as appropriate replacement for oral busulfan in pretransplant conditioning therapy prior to allogeneic BMT for patients with AML or MDS.
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PMID:Allogeneic stem cell transplantation (BMT) for AML and MDS following i.v. busulfan and cyclophosphamide (i.v. BuCy). 1093 85

Actinomycin-D (Act-D) is a rare cause of veno-occlusive disease (VOD). Between 1993 and 1998, we managed 6 patients, all male, median age 19 months (range 6-48 months) who received Act-D for Wilms' tumour (n=4), clear cell sarcoma (n=1) or rhabdomyosarcoma (n=1). VOD presented with a median platelet count of 12 x 10(9)/l, INR 3.8, fibrinogen 16 mg/l, fibrinogen degradation products (FDPs) > or =80 microg/l, aspartate aminotransferase (AST) 6922 IU/l, bilirubin 47 micromol/l. In 3 cases, transient liver dysfunction and thrombocytopenia without neutropenia had been observed after a previous course of Act-D. All six children developed encephalopathy, hepatomegaly, ascites, reversed portal flow and renal impairment. All received mechanical ventilation and two required haemofiltration. The treatment was supportive. Severe Adult Respiratory Distress Syndrome developed in 3 patients, all of whom died. 3 patients recovered. The outcome of VOD with multi-organ failure is poor. Intravascular coagulopathy precedes and characterises severe VOD during Act-D treatment.
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PMID:Veno-occlusive disease with multi-organ involvement following actinomycin-D. 1137 45

Granulocyte-macrophage (GM-CSF) and granulocyte colony-stimulating factors (G-CSF) are equally effective hematopoietic growth factors in terms of their potential to shorten the period of neutropenia following high-dose chemotherapy or to mobilize hematopoietic stem cells. Thus the choice between the two preparations must be based on a comparison of adverse effects. Both GM-CSF and G-CSF have been implicated in disturbances of the hemostatic system, resulting in both hemorrhagic and thrombotic complications. We therefore studied the effects of GM-CSF and G-CSF therapy on hemostasis both ex vivo and clinically. In a prospective, non-randomized study 34 patients who were treated with a myeloablative regimen according to the hyper-ME+/-C protocol and stem cell or bone marrow transplantation received posttransplantation hematopoietic support with GM-CSF (n=15) or G-CSF (n=19). The patients were monitored for alterations in plasmatic coagulation parameters and clinical evidence of hemorrhagic or thrombotic events. GM-CSF, but not G-CSF, induced a significant, albeit usually mild activation of the coagulation cascade. We observed an increased frequency of veno-occlusive disease in the GM-CSF group (3/15 vs. 1/19 on G-CSF, n.s.). Other thrombotic events were rare. At the same time, hemorrhage was both more common and more severe in GM-CSF treated patients than in those on G-CSF (macroscopic hemorrhage 11/15 vs. 10/19, III hemorrhage 7/15 vs. 1/19 on GM-CSF or G-CSF, respectively). In conclusion, unlike G-CSF, if given after hyper-ME chemotherapy plus stem cell or bone marrow transplantation, at the dosage used here GM-CSF induced an activation of the coagulation system and was associated with an increased risk of hemostasis associated treatment complications.
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PMID:Growth factors and hemostasis: differential effects of GM-CSF and G-CSF on coagulation activation--laboratory and clinical evidence. 1166 1

Acute complications such as veno-occlusive disease of the liver, acute and chronic graft-vs-host disease (GVHD), and infectious conditions remain major obstacles for the success of allogeneic hematopoietic stem cell transplantation (HSCT). Progress in allogeneic HSCT depends on several factors, including the adequate prevention and management of associated complications, advances in the conventional management of diseases currently treated with allogeneic HSCT, expansion of the donor pool, selective control of GVHD, development of more effective preparative regimens to eradicate the neoplastic cell population, characterization of a new generation of hematopoietic growth factors and cytokines, and development of newer techniques for ex vivo manipulation of stem cells. Hematopoietic growth factor-mobilized donor progenitor cells collected from peripheral blood have been shown to be associated with rapid hematopoietic engraftment without an increase in the incidence of acute GVHD compared with allogeneic bone marrow transplantation. Implementation of this approach will enhance donor acceptance, eliminate the risk of general anesthesia, decrease cost, and reduce the risk of infectious complications by reducing the duration of neutropenia. Nonmyeloablative allogeneic stem cell transplantation represents a novel treatment approach that may lead to reduced toxic effects and extended use of this treatment in older patients and in those with malignant and nonmalignant disorders. However, GVHD and disease recurrence remain a challenge. Promising results have been reported in patients with refractory hematologic malignancies and in metastatic renal cell cancer. Because late complications are commonly encountered in patients receiving allogeneic HSCT, lifelong observation is needed.
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PMID:Allogeneic hematopoietic stem cell transplantation: complications and results. 1212 98

Antibody-targeted chemotherapy is a promising approach in patients with hematological malignancies. In particular, gemtuzumab ozogamicin (GO, formerly CMA-676), an anti-CD33 antibody linked to calicheamicin, has been approved for the treatment of elderly patients with acute myeloid leukemia (AML) in relapse. Nevertheless, no data are until now available concerning the possible efficacy of GO for myeloid sarcomas (MS). We treated with GO 24 AML patients, in 5 cases presenting with myeloid sarcomas of the skin or bones. The overall complete response rate was 21%. The median duration of response was 6 months. Four out of the 5 patients with myeloid sarcoma showed a regression of the masses, in two cases also obtaining a clearance of marrow blasts. The most common adverse events included thrombocytopenia, neutropenia, infections, elevation of bilirubin and hepatic transaminases. Notably, severe bleeding occurred in 5 cases (21%). VOD was documented in 1 case. We conclude that GO is effective as a single agent in AML and myeloid sarcomas. Further data are required to clarify the possible correlation between GO administration and occurrence of bleeding.
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PMID:Gemtuzumab ozogamicin for relapsed and refractory acute myeloid leukemia and myeloid sarcomas. 1522 37

Pivotal phase II studies in acute myeloblastic leukemia (AML) patients in first relapse have used gemtuzumab ozogamicin (GO) (Mylotarg) at a dose of 9 mg/m(2) on days 1 and 14. These studies showed a 26% response rate (13% complete remission (CR) and 13% CRp (complete remission with incomplete platelet recovery)) but with high degree of hematological and liver toxicities. Based on in vitro studies showing a re-expression of CD33 antigenic sites on the cell surface of blasts cells after exposure to GO, we hypothesized that fractionated doses of GO may be efficient and better tolerated. Fifty-seven patients with AML in first relapse received GO at a dose of 3 mg/m(2) on days 1, 4 and 7 for one course. Fifteen patients (26%) achieved CR and four (7%) CRp. Remission rate correlated strongly with P-glycoprotein and MRP1 activities. The median relapse-free survival was 11 months, similar for CR or CRp patients. Median duration of neutropenia < 500/microl and thrombocytopenia < 50,000/microl were, respectively, 23 and 21 days. No grade 3 or 4 liver toxicity was observed. No veno-occlusive disease occurred after GO or after hematopoietic stem cell transplantation given after GO in seven patients. Mylotarg administered in fractionated doses demonstrated an excellent efficacy/safety profile.
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PMID:High efficacy and safety profile of fractionated doses of Mylotarg as induction therapy in patients with relapsed acute myeloblastic leukemia: a prospective study of the alfa group. 1705 Dec 46


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