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KEY CONCEPTS

  • The use of autologous hematopoietic progenitor-cell transplant (AHPCT) overcomes myelotoxicity of high-dose chemotherapy (HDC). Therefore, drugs with a markedly myelosuppressive side effect profile and a steep dose-response effect are preferred. The most common nonhematologic regimen-related toxicity (RRT) is oropharyngeal mucositis, which is rarely life threatening. The most common among the potentially severe extramedullary RRT are interstitial pneumonitis and veno-occlusive disease of the liver.

  • HDC with AHPCT has been the standard of care for chemosensitive, relapsed diffuse large B-cell lymphoma (DLBCL) for the last three decades. However, the results remain suboptimal in patients whose disease relapses less than one year after completion of frontline chemoimmunotherapy (eg, R-CHOP).

  • In follicular lymphoma, HDC with AHPCT should be considered for high-risk relapses occurring within two years of completing frontline therapy (POD24) or second or more advanced relapses.

  • Management of relapsed or primary refractory Hodgkin lymphoma in patients should be a salvage strategy using one or more lines of therapy, including regimens such as bendamustine/brentuximab vedotin or ifosfamide/carboplatin/etoposide aiming at a positron emission tomography–negative remission before AHPCT. Patients with a high-risk for disease relapse should be considered for post-AHPCT maintenance with brentuximab vedotin.

  • Modern treatment of newly diagnosed myeloma should include induction with a proteasome inhibitor and an immunomodulatory drug (eg, bortezomib/lenalidomide/dexamethasone [VRD]) followed by melphalan-based HDC and AHCPT, and consolidation and/or maintenance with drugs like lenalidomide, with the goal of achieving a minimal residual disease-negative remission.

  • Tandem cycles of carboplatin-containing HDC with AHPCT should be considered for any patient with a germ-cell tumor in the second or later relapse. Their role in the first relapse is still undetermined.

BASIC CONCEPTS

High-dose chemotherapy (HDC) with autologous hematopoietic progenitor-cell transplant (AHPCT) is an effective treatment modality for a variety of hematologic malignancies and selected solid tumors. This chapter reviews its current role in the treatment of cancer, outlining future directions of progress.

Doses of radiation and chemotherapy are limited by toxicity to normal tissues and, particularly, the bone marrow. However, the doses of certain chemotherapeutic agents and radiation can be substantially escalated, exploiting their dose-response effect, when followed by autologous or allogeneic transplantation of HPCs to restore hematopoiesis. Pluripotent HPC progenitors present in the graft proliferate and differentiate into the mature blood and immune cells. AHPCT involves the collection, cryopreservation, and infusion of the patient's own HPCs.

GENERAL PROCEDURES FOR AUTOLOGOUS TRANSPLANTATION

Figure 18–1 shows the different procedures related to autologous transplantation.

FIGURE 18–1

Autologous hematopoietic progenitor-cell transplantation process.

Preceding Standard-Dose Chemotherapy

Standard-dose chemotherapy is usually given to cytoreduce the tumor before proceeding to AHPCT. In general, the best outcomes are seen in patients with chemosensitive disease in complete remission, or with minimal tumor burden at the time of transplantation.

Peripheral Blood Progenitor Cell Collection

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