Unique gene expression and clinical characteristics are associated with the 11q23 deletion in chronic lymphocytic leukaemia.

Chromosome abnormalities influence prognosis and tumour progression in B-cell Chronic Lymphocytic Leukaemia (CLL). This study sought to determine whether these different disease subgroups were associated with unique gene expression patterns. Thirty-four cases of CLL were screened for the 11q23, 13q14, 17p13 deletions, and trisomy 12 by fluorescence in situ hybridization (FISH).

Immunological and clinical effects of post-transplant G-CSF versus placebo in T-cell replete allogeneic blood transplant patients: results from a randomized double-blind study.

Background: Immunological and clinical effects of post-transplant growth factor administration have not been well studied. This report describes the outcome and immune functions of a total of 50 HLA-matched related donor allogeneic blood stem-cell transplantation patients who received post-transplant G-CSF (10 microg/kg) or placebo.

Methods: Immune status, including number of lymphocyte subsets and their functions, and serum immunoglobulin levels and clinical status--including GvHD, rate of relapse, event-free survival, and overall survival--were determined in the patients enrolled in this study.

Increased apoptosis in B-chronic lymphocytic leukemia cells as a result of cyclin D3 down regulation.

B-cell chronic lymphocytic leukemia (CLL) is a clonal B cell malignancy of morphologically mature, functionally immature B cells. B-cell CLL cells are known to be resistant to killing by anticancer and other agents. This resistance is associated with alterations in apoptosis and cell cycle regulated genes.

Increased cytotoxicity against B-chronic lymphocytic leukemia by cellular manipulations: potentials for therapeutic use.

B-cell chronic lymphocytic leukemia (CLL) is characterized by profound immune dysfunction and a marked resistance to apoptosis. Understanding the cellular biology of immune effector cells from CLL patients as well as leukemic target cells is essential to developing immune mediated therapeutic strategies for CLL. In this study, an immortal CLL cell line called WSU-CLL has been used to study the characteristics of B-cell CLL as a tumor target for natural killer (NK), activated natural killer, and lymphokine activated killer (LAK) cells.

Blood stem cell transplantation: factors influencing cellular immunological reconstitution.

Recovery of immune function following stem cell transplantation is necessary for a good outcome. Immune recovery is facilitated by transplanting higher numbers of cells than neutrophil or platelet reconstitution requires. Estimates from studies in the allogeneic setting suggest the minimum stem cell dose to achieve optimal lymphocyte recovery is about 10(7) CD34+ cells/kg.

A randomized, double-blind trial of filgrastim (granulocyte colony-stimulating factor) versus placebo following allogeneic blood stem cell transplantation.

Blood stem cell transplantation (BSCT) results in rapid hematopoietic recovery in both the allogeneic and autologous transplant settings. Because of the large numbers of progenitor cells in mobilized blood, the administration of growth factors after transplantation may not provide further acceleration of hematopoietic recovery. A randomized, double-blind, placebo-controlled study was performed to determine the effects of filgrastim (granulocyte colony-stimulating factor; G-CSF) administration on hematopoietic recovery after allogeneic BSCT.

Filgrastim as an alternative to donor leukocyte infusion for relapse after allogeneic stem-cell transplantation.

Purpose: Donor leukocyte infusion (DLI) effectively treats relapse after allogeneic stem-cell transplantation (alloSCT), but the response may require several months and may be associated with significant toxicity. Filgrastim has also been observed to effectively treat leukemic relapse after alloSCT. A retrospective analysis was performed to determine the effectiveness of filgrastim in treating relapses after alloSCT.

Outcome of allogeneic stem cell transplantation for B cell chronic lymphocytic leukemia.

The objective of this study was to describe the outcome of allogeneic stem cell transplantation (alloSCT) in a series of patients with B cell chronic lymphocytic leukemia (B-CLL). Twenty-three B-CLL patients were transplanted between 1988 and 1997 using stem cells from a related (n = 20) or an unrelated donor (n = 3). The median age of the patients was 46 years, and the median number of prior chemotherapy regimens received was two.

Central nervous system dysfunction as the first manifestation of multiple organ dysfunction syndrome in stem cell transplant patients.

Development of CNS dysfunction in the setting of hematopoietic stem cell transplant (HSCT) has been previously shown to predict for subsequent second organ dysfunction and death. In this paper, we describe the characteristics of this isolated CNS dysfunction, and its relationship to multiple organ dysfunction syndrome (MODS) after HSCT. Twenty-one of 186 patients undergoing HSCT developed CNS dysfunction as their first organ dysfunction a mean of 22.

Valuing clinical strategies early in development: a cost analysis of allogeneic peripheral blood stem cell transplantation.

Allogeneic peripheral blood stem cell transplantation (alloPBSCT) is an emerging technology. As this technology develops, transplant centers are concerned with looking for technologic advances that will result in improvements in clinical outcomes and lower costs. We provide comparative estimates of costs and resource use for alloPBSCT in comparison to allogeneic bone marrow transplantation (alloBMT) for persons with hematologic malignancies from the time of harvest to 100 days post transplant.

A prospective randomized double-blind trial of antithrombin III concentrate in the treatment of multiple-organ dysfunction syndrome during hematopoietic stem cell transplantation.

Many of the complications of high-dose therapy with hematopoietic stem cells are caused by or lead to the multiple-organ dysfunction syndrome (MODS). In hematopoietic stem cell transplantation (HSCT), acquired antithrombin III (ATIII) deficiency is independently associated with MODS to the exclusion of transplant type, preparative regimen, and bacteremia. In experimental settings, replacement of ATIII can ameliorate the severity of MODS that develops in response to a variety of pathologic stimuli, suggesting that ATIII supplementation might improve the clinical course of MODS in patients undergoing HSCT.

High incidence of relapse after autologous stem-cell transplantation for B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma.

Background: High-dose therapy followed by autologous stem-cell transplantation (autoSCT) induces complete remissions in the majority of patients with advanced B-cell chronic lymphocytic leukemia or small lymphocytic lymphoma (B-CLL). However, the long-term utility of this therapy for B-CLL is unknown.

Patients And Methods: Sixteen previously treated patients with B-CLL were transplanted using autologous blood (n = 13) or bone marrow (n = 3).

Lymphocyte reconstitution after allogeneic blood stem cell transplantation for hematologic malignancies.

Forty-one patients were studied at set times after allogeneic blood stem cell transplantation (alloBSCT) for recovery of lymphocyte numbers and function. Cells were mobilized with G-CSF from HLA-matched related donors and cryopreserved. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and methotrexate; G-CSF was administered post-transplant.

Hematopoietic recovery after allogeneic blood stem-cell transplantation compared with bone marrow transplantation in patients with hematologic malignancies.

Purpose: To compare hematopoietic recovery, duration of hospitalization, and 100-day survival in patients who received allogeneic-blood stem cells (BSC) or conventional allogeneic bone marrow transplantation (BMT).

Patients And Methods: From December 1994 to August 1995, 21 patients participated in a phase II study of allogeneic BSC transplantation. Cells mobilized with granulocyte colony-stimulating factor (G-CSF; 5 micrograms/kg/ d) were collected from human leukocyte antigen (HLA)-matched related donors and cryopreserved.

Allogeneic-blood stem-cell collection following mobilization with low-dose granulocyte colony-stimulating factor.

Purpose: The optimal dose of granulocyte colony-stimulating factor (G-CSF) for mobilization of allogeneic-blood stem cells (AlloBSC) has yet to be determined. As part of a prospective trial, 41 related human leukocyte antigen (HLA)-matched donors had blood cells mobilized with G-CSF at 5 micrograms/kg/d by subcutaneous administration. The purpose of this trial was to monitor adverse effects during G-CSF administration and stem-cell collection, to determine the optimal timing for stem-cell collection, and to determine the cellular composition of stem-cell products following G-CSF administration.

Drug-induced parkinsonism after allogeneic bone marrow transplantation.

We report a severe case of drug-induced parkinsonism (DIP) after allogeneic BMT successfully treated with levodopa. BMT patients typically receive numerous medications which can cause DIP, and mild cases of DIP may remain unrecognized or be misdiagnosed. Physicians should be aware of DIP as a potential neurological complication after BMT to avoid further administration of drugs that could aggravate symptoms.

Bone Marrow Transplantation for Cancer - An Update.

The number of allogeneic and autologous bone marrow transplants continues to grow worldwide. Bone marrow transplantation (BMT) has become standard therapy for many patients with leukemia, lymphoma, multiple myeloma and testicular cancer. Encouraging results of autologous BMT in treating patients with poor-risk breast cancer have led to this approach being tested in nationwide randomized trials.

Bone marrow transplantation in chronic lymphocytic leukemia and lymphomas.

Until recently younger patients with B-cell chronic lymphocytic leukemia (CLL) have not been considered for treatment with high-dose therapy and bone marrow transplantation (BMT). Current results show that both autologous and allogeneic bone marrow transplantation can induce a high percentage of long lasting remissions in younger patients with poor-risk CLL. Because of the investigational character of BMT for CLL, all eligible patients should be enrolled in clinical trials.

Induction by interleukin-7 of lymphokine-activated killer activity in lymphocytes from autologous and syngeneic marrow transplant recipients before and after systemic interleukin-2 therapy.

Therapy with recombinant lymphokines after autologous bone marrow transplantation (ABMT) is being explored as a way to prevent relapse. Lymphokine therapy may exert an antitumor effect through a variety of mechanisms, including the induction of lymphokine-activated killer (LAK) cell cytotoxicity. We tested the ability of interleukin-7 (IL-7) to induce LAK cytotoxicity in peripheral blood mononuclear cells (PBMC) from healthy subjects and from patients early after ABMT.

Prostaglandin E2 for prophylaxis of oral mucositis following BMT.

Between October 1988 and December 1990, 60 patients with leukaemia (25 with AML, 19 ALL and 16 CML) undergoing BMT were randomised in a double-blind clinical trial to receive prostaglandin E2 (PGE) (Prostin E2, 0.5 mg per tablet) or placebo for prophylaxis of oral mucositis. Patients had to dissolve tablets in the mouth three times daily starting 7 days before BMT and continuing until 21 days after BMT.

Antilymphocyte globulin for treatment of pure red cell aplasia after major ABO incompatible marrow transplant.

A patient developed pure red cell aplasia after ABO incompatible BMT for leukemia. He did not respond to plasma exchange. Antilymphocyte globulin therapy was followed by complete and permanent erythroid recovery with disappearance of recipient-derived isoagglutinins.

[Hematopoietic growth factors].

Hematopoietic growth factors are glycoproteins that stimulate the proliferation and differentiation of hematopoietic progenitor cells. Due to several technical advances, first of all to the techniques of recombinant DNA, it has become possible today to produce them highly-purified and in amounts big enough to enable its application in clinical trials. Until now, 5 hematopoietic growth factors have been studied on humans.

Combination of cyclosporin and methotrexate for prophylaxis of acute graft-versus-host disease after allogeneic bone marrow transplantation for leukemia.

From May 1985 to July 1989, 76 patients with leukemia (30 acute myelogenous leukemia, 24 acute lymphoblastic leukemia and 22 chronic myeloid leukemia) were randomized to receive either cyclosporin (CSP) alone (n = 39) or CSP combined with methotrexate (CSP + MTX, n = 37) for graft-versus-host disease (GVHD) prophylaxis. Patients were conditioned with total body radiation and cyclophosphamide followed by bone marrow infusion from an HLA-identical sibling. Engraftment of the transplanted bone marrow was similar in both groups.

Relationship between differing volumes of bone marrow aspirates and their cellular composition.

We compared the cellular composition of the first 1.0 ml volume bone marrow aspirate with that of an aliquot from the total bone marrow harvest at the end of the procedure in 17 healthy bone marrow donors. Each sample was assayed for its content of red blood cells, nucleated cells, CD2+, CD4+, CD8+, CD19+, HLA-DR+, CD56+, CD13+, CD33+, CD34+ and KiM8+ cells and CFU-GM.