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Mobilized CD34+ cells selected as autografts in patients with primary light-chain amyloidosis: rationale and application

Authors


Transfusion Medicine Program, Department of Pathology and Laboratory Medicine, and Associate Director, Stem-Cell Transplant Program, Section of Hematology-Oncology, Department of Medicine, Boston Medical Center and Boston University School of Medicine, H-303, 88 East Newton Street, Boston, MA 02118–2393.

Abstract

BACKGROUND: Concern about tumor cell contamination in stem cell preparations has led to the use of CD34+ cell selection as a means of purging. Increasing the number of CD34+ cells per leukapheresis may help to provide an adequate dose of CD34+ cells. STUDY DESIGN AND METHODS: The reverse transcriptase polymerase chain reaction (RT-PCR) was employed to clone overexpressed clonotypic immunoglobulin light- chain variable region genes (Ig VL) from bone marrows of patients with primary light-chain amyloidosis (AL). Patient-specific primers were designed to evaluate stem cell collections for contamination. CD34+ cell selection was performed on components from AL patients who underwent mobilization with granulocyte-colony-stimulating factor (G- CSF) (filgrastim; 16 microg/kg/d for 4 days) and collection by large- volume leukapheresis (LVL;25L) on Days 4 and 5. The selected cells alone were transfused after patients received mephalan (200 mg/m2). RESULTS: Contamination was found in collections from 4 to 7 patients, which provided the rationale for a subsequent trial of CD34+ cell selection. The median number of CD34+ cells per kg collected on Days 4 and 5, and in toto, was 4.0 × 10(6)(1.1-12.7), 7.9 × 10(6)(1.8-12.7), and 10.7 × 10(6)(2.9-25.4), respectively (n = 9 patients). The median yield per selection was 38 percent, with a purity of 85 percent (45- 97%), and the viability of CD34+ cells averaged 96.4 +/− 3.6 percent (n = 18 selections). The median number of CD34+ cells infused was 5.9 × 10(6) per kg (2.1-10.1). In comparison with AL patients given unselected autografts, patients receiving selected CD34+ cells experienced similar reconstitution of neutrophils and platelets but slower lymphocyte recovery. CONCLUSION: Patients with AL often have contamination with clonotypic cells in their blood autografts. G-CSF mobilization and LVL provide components that allow the selection of adequate doses of CD34+ cells. The use of CD34+ cells in patients with AL achieves rapid neutrophil and platelet recovery but delayed lymphocyte recovery. CD34+ cell selection is feasible in the treatment of AL, but its effectiveness in purging clonotypic cells remains to be ascertained.

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