難治性悪性リンパ腫に対する免疫磁気ビーズ法によるCD34陽性純化自家末梢血幹細胞移植併用の超大量化学放射線療法(臨床第I/II相試験)

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This multicenter phaise I/II clinical trial was conclucted to evaluate the safety of a device (Isolex 50 : Baxter) that uses the immunomagnetic bead method to purify CD 34-positive stem cells from peripheral blood, and to assess the efficacy and toxicity of high-dose chemoradiotherapy with peripheral blood stem cell transplantation (PBSCT) using the purified CD 34-positive stem cells in patients with refractory malignant lymphomas. The criteria of patients' eligibility were as follows : 1) T-ALL, lymphoblastic lymphoma (LBL), mantle cell lymphoma, high risk group of aggressive NHL, and ATLL in first CR ; 2) standard risk group of aggressive NHL, or indolent lymphoma, or Hodgkin's disease, or APL in second CR or first PR (after the completion of front-line chemotherapy, and chemosensitive to salvage chemotherapy) ; 3) the possibility of tumor contamination in harvesting PBSC because of bone marrow or peripheral blood involvement ; 4) no expression of CD 34 in tumor cells ; 5) age from 15 to 54 ; 6) performance status of 0 to 1 with no dysfunction of major organs ; 7) no allogeneic donor ; 8) written informed consent of the patient. Ten patients with hematological malignancies (2 T-lymphoblastic lymphoma patients in 1st CR, 1 ATLL in 1st CR, 1 mantle cell lymphoma in 1st PR. 3 follicular lymphomas in 2nd CR or PR, 1 NK lymphoma in 2nd CR, 1 diffuse large cell lymphoma in 2nd CR, and 1 APL in 2nd CR) were enrolled. The patients' median age was 43 years (range, 26 to 50). Consolidation and mobilization chemotherapy were as follows : MEVP (MIT, VP-16, VCR and PDN), DCVP (DNR, Ara-C, VDS and PDN), CHASE (CPA. Ara-C, VP-16 and DXM) for LBL, biweekly CHOP for mantle cell lymphoma and ATLL, CHASE or Mit-Ara-C, for follicular lymphomas, Ara-C + VP-16 or high-dose VP-16 for NK lymphoma, and BHAC and DNR/ Mit for APL. Two to three courses of apheresis were performed for each patient. A median number of 2.02 × 10^6 cells/kg of CD 34-positive cells were purified and infused in each patient. After the high-dose chemoradiotherapy (6 L-PAM/TBI, 3 CPA/VP-16/L-PAM, and 1 Bu/L-PAM/TBI) for all patients, purified CD 34 positive PBSCs were infused and G-CSF was given from day 1. Hematopoietic recovery was as follows (median) : WBC >1,000/μl : day 11, Plt >5,000/μl : day 17, Ret >10%_0 : day 15. Four patients with follicular lymphoma, NK lymphoma, ATLL and diffuse large-cell lymphoma relapsed at 5, 9, 9 and 5 months after PBSCT, respectively Another six patients are alive in CR. Although interstitial pneumonla, hemorrhagic cystitis, pericarditis herpes zoster infection and CMV infection occurred in six patients, they recovered rapidly. No severe complications were observed in the other four patients. Although tumor contamination assessable through a PCR-mediated RNase protection assay at level 10^<-4> was detected in 2 of the 5 analyzed CD 34^+purified fractions, a greater than 3- to 4-log reduction in contaminating lymphoma cells from autograft was achieved using CD 34-positive selection with the immunomagnetic bead method. High-dose chemoradiotherapy with CD 34-positive peripheral blood stem cell transplantation using the immunomagnetic bead method showed an active and safe therapy for refractory hematological malignancies with bone marrow or peripheral blood involvement by tumor cells. However, it is too early for the evaluation of long-term survival benefits.
日本アフェレシス学会の論文
1999-11-30

難治性悪性リンパ腫に対する免疫磁気ビーズ法によるCD34陽性純化自家末梢血幹細胞移植併用の超大量化学放射線療法(臨床第I/II相試験)

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