Biomedical subjects

Richard Champlin

Publications and source records attributed to Richard Champlin.

40 records · Page 3Linked to original sources

PubMed2002

Use of thrombopoietin in combination with chemotherapy and granulocyte colony-stimulating factor for peripheral blood progenitor cell mobilization.

This phase I/II dose-escalation study examined the safety and efficacy of recombinant human thrombopoietin (rhTPO) and granulocyte colony-stimulating factor (G-CSF) for postchemotherapy mobilization of peripheral blood progenitor cells (PBPCs) in patients with advanced breast cancer. Patients received cyclophosphamide, etoposide, and cisplatin (CVP) followed by G-CSF (6 microg/kg twice a day) and rhTPO (0.6, 1.2, 2.4, or 3.6 microg/kg as a single dose on day 5 or as 3 doses on days 5, 7, and 9 after chemotherapy). PBPCs were collected by daily leukapheresis when the postnadir white blood cell count reached > or = 2 x 10(9)/L; leukapheresis was continued until acquisition of a target dose of > or = 5 x 10(6) CD34+ cells/kg. Mobilized PBPCs were transplanted into patients after additional high-dose chemotherapy with cyclophosphamide, carmustine, and thiotepa (CBT). Comparisons were made with contemporaneously treated, nonrandomized, control patients who received the same chemotherapy regimens and G-CSF support but who did not receive rhTPO. Of 32 evaluable patients receiving rhTPO and G-CSF after CVP, 91% required only 1 leukapheresis to achieve a target PBPC graft; by contrast, only 69% of 36 of the control patients achieved the target graft with just 1 leukapheresis (P = .026). A median of 26.7 x 10(6) CD34 cells/kg per leukapheresis was obtained from the rhTPO-treated patients compared with 11.5 x 10(6) cells/kg per leukapheresis from the controls (P = .09). Higher rhTPO doses appeared to yield more CD34+ cells. When PBPCs were infused after high-dose CBT chemotherapy, the median times to return of an absolute neutrophil count of 0.5 x 10(9)/L and a platelet count of 20 x 10(9)/L were 15 and 16 days, respectively; these values did not differ from those in the control group (15 days for both neutrophil and platelets). No patient developed anti-TPO antibodies. These results indicate that rhTPO safely and effectively augments the number of PBPCs mobilized with chemotherapy and G-CSF and can reduce the required number of leukaphereses. Further studies are also warranted in patients who are likely to experience suboptimal PBPC mobilization when treated with currently available techniques.

Adult↗

PubMed2002

Nonablative stem cell transplantation for older patients with acute leukemias and myelodysplastic syndromes.

High-dose chemoradiotherapy with allogeneic bone marrow or peripheral blood stem cell transplantation (SCT) is a potentially curative treatment for advanced or poor-prognosis hematological malignancies. This procedure was initially considered as a means to deliver supralethal doses of chemotherapy and radiation for the eradication of the malignancy, but it has subsequently become apparent that much of the therapeutic benefit of SCT relates to an associated immune-mediated graft-versus-leukemia (GVL) effect. Additionally, due to the increased risk of morbidity and graft-versus-host disease (GVHD) that occurs with advanced age, the use of standard myeloablative preparative regimens with allogeneic progenitor cell transplantation has been generally limited to younger patients in good medical condition. However, most patients with hematologic malignancies are older and therefore the overall impact of allografting is relatively small. Thus despite resulting in high rates of long term disease control, allografting is only performed in a small fraction of patients, either because of lack of a suitable donor or the high risk of toxicity due to age or the general medical condition. Therefore strategies aimed at improving the safety and tolerability of allografting to allow for its more frequent application in older patients are necessary.

Acute Disease↗

PubMed2002

Use of filgrastim for stem cell mobilisation and transplantation in high-dose cancer chemotherapy.

Myeloablative or high-dose chemotherapy regimens utilise doses that are significantly greater than those used in standard treatments. The neutropenia caused by these high-dose therapies can be associated with an increased incidence of bacterial and fungal infections and remains an important clinical issue among patients with advanced-stage cancers. Filgrastim is approved for stem cell mobilisation in both chemotherapy-treated patients and normal donors. Harvested peripheral blood progenitor cells have been used effectively in allogeneic and autologous transplantation, increasing the speed and extent of neutrophil and platelet recovery. Accelerated haematopoietic recovery is associated with a significantly shorter hospital stay and, therefore, leads to a reduction in treatment costs. The contribution of filgrastim to the acceleration of haematopoietic recovery after peripheral blood progenitor cell transplant has been assessed in a number of prospective clinical trials after high-dose chemotherapy. Controversy remains over whether growth factors should be administered shortly after stem cell infusion or after several days. The recently approved, once-weekly form of filgrastim, pegfilgrastim, has been shown to have efficacy comparable to that of the native molecule and can be expected to enhance patient quality of life through the need for fewer injections. This article will review the role of filgrastim for stem cell mobilisation and transplantation in patients receiving high-dose chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2000

Managing Indolent Lymphomas in Relapse: Working Our Way Through a Plethora of Options.

The front-line management of stage IV indolent non-Hodgkin's lymphoma has ranged from the watch-and-wait approach to intensive experimental regimens such as high-dose chemotherapy and bone marrow transplant. With this broad spectrum of regimens to choose from the decision has become a challenging exercise for both patients and oncologists. With the recent introduction of new agents such as rituximab, fludarabine, and combinations based on these, the management of relapsed cases can be similarly confusing. More aggressive approaches such as high-dose chemotherapy with autologous bone marrow transplant and more recently allogeneic bone marrow transplant have also been used. Recently the technique of "mini-allo transplants" has been introduced. It utilizes a less myelosuppressive conditioning chemotherapy regimen based on fludarabine which is immunosuppressive enough to allow engraftment of the donor marrow. Since it is less myelotoxic it is better tolerated, and this has allowed us to significantly extend the age cut-off for allogeneic transplants. All these advances provide us with a more extensive armamentarium, but at the same time they confront physicians with new challenges in choosing from a large and continuously growing therapeutic menu. In this review of the alternative therapies a panel of three expert hemato-oncologists each discuss their approach to the management of a 49-year-old patient with a relapsed indolent follicular lymphoma. Dr. Horning discusses the traditional alternatives available for this patient such as standard chemotherapy combinations or the watch-and-wait approach in Section I. In Section II, Dr. Kaminski reviews the different therapeutic monoclonal antibody options such as rituximab, Bexxar (Iodine-labeled anti-CD20) and Ytrium-labeled anti-CD20 antibody. Allogeneic transplants are increasingly more popular for the treatment of indolent lymphomas because they can provide an immune-mediated graft-versus-lymphoma effect. In Section III, Dr. Richard Champlin reviews various transplant options including autologous, allogeneic and mini-allogeneic transplants.

Journal Article↗