Autologous bone marrow transplantation using marrow incubated with Asta Z 7557 in adult acute leukemia.
Autologous bone marrow transplantation using marrow incubated with Asta Z 7557 in adult acute leukemia.
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使用 Asta Z 7557 孵育的骨髓对成人急性白血病进行自体骨髓移植。
DOI：
10.1182/blood.v67.5.1367.bloodjournal6751367
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发表时间：
1986
期刊：
影响因子：
20.3
通讯作者：
R. David
中科院分区：
文献类型：
--
作者：
N. Gorin;L. Douay;J. Laporte;M. Lopez;J. Mary;A. Najman;C. Salmon;P. Aegerter;J. Stachowiak;R. David
研究了人成粒细胞白血病 (CFU-L) 和正常造血干细胞 (CFU-GM 和 BFU-e) 对 Asta Z 7557 (INN Mafosfamide) 的敏感性，研究涉及使用清洁骨髓的自体骨髓移植 (ABMT)，用于缓解期急性白血病 (AL) 成年患者的巩固治疗。 CFU-GM (n = 37)、BFUe (n = 11) 和成髓细胞 CFU-L (n = 9) 剂量反应曲线的建立证明了患者与患者之间对所有三种祖细胞的广泛敏感性。尽管在半固体培养物中生长的 CFU-L、CFU-GM 和 BFU-e 显示出与 Asta Z 7557 相似的敏感性，但长期培养 (LTC) 研究 (n = 41) 表明早期祖细胞具有更高的耐药性。为了实现最大程度的肿瘤细胞杀灭，同时保留足够量的正常干细胞以确保一致的移植，我们将骨髓净化的最佳剂量定义为保留 5% CFU-GM (LD95) 的剂量。该剂量是根据每位患者在骨髓采集前 15 天采集的 10 mL 骨髓抽吸物进行的预孵育测试 (PIT) 确定的。 24 名 AL 缓解期成年患者（20 名完全缓解，4 名部分缓解）通过环磷酰胺 60 mg/kg X 2 和 10 Gy 全身照射进行巩固，然后根据上述规范进行 ABMT，并使用 Asta Z 7557 清洁骨髓。患者被分为两组：第1组，预后不良（11名患者）；第2组，预后不良（11名患者）。第2组，标准预后[13名患者首次完全缓解（CR）]。所有患者均接受白细胞移植（恢复至 10(9)/L 的中位天数：第 30 天），ALL 患者比 ANL 患者恢复得更快（中位天数 19 vs 34）。同样，ALL 患者的血小板恢复到 50.10(9)/L 的速度更快（中位第 67 天，范围为第 23 至 90 天），而第 2 组中的 3 名急性非淋巴细胞白血病 (ANLL) 患者必须接受血小板输注一年多。第1组中有6名患者在6个月内肿瘤复发；三名患者死于毒性，但没有发现肿瘤的证据。两名患者在短期随访（九个月和十个月）后仍然没有疾病。在第 2 组中，两名患者在 ABMT 后 3 个月和 16 个月因毒性死亡，且没有任何白血病证据。一名 M5 ANLL 患者和一名 ALL 患者分别在 6 个月和 15 个月时复发。中位随访 22 个月后，9 名患者仍处于 CR 状态或无疾病。（摘要截断为 400 字）
The sensitivity of human myeloblastic leukemic (CFU-L) and normal hemopoietic stem cells (CFU-GM and BFU-e) to Asta Z 7557 (INN Mafosfamide) was studied with regard to autologous bone marrow transplantation (ABMT) with cleansed marrow for consolidation therapy in adult patients with acute leukemia (AL) in remission. Establishment of the dose-response curves for CFU-GM (n = 37), BFUe (n = 11), and myeloblastic CFU-L (n = 9) demonstrated a wide range of sensitivity from patient to patient for all three progenitors. Whereas CFU-L, CFU-GM, and BFU-e grown in semisolid cultures disclosed similar sensitivities to Asta Z 7557, long-term culture (LTC) studies (n = 41) indicated a higher resistance of early progenitors. In an effort to achieve a maximum tumor cell kill and yet spare a sufficient amount of normal stem cells to ensure consistent engraftment, we defined the optimal dose for marrow cleansing as the dose sparing 5% CFU-GM (LD95). This dose was established from a preincubation test (PIT) realized on a 10-mL marrow aspirate taken 15 days before marrow collection in each individual patient. Twenty-four adult patients while in remission of AL (20 in complete remission, four in partial remission) were consolidated by cyclophosphamide 60 mg/kg X 2 and total body irradiation at 10 Gy followed by ABMT with marrow cleansed by Asta Z 7557 according to the specification described above. Patients were divided in two groups: group 1, unfavorable prognosis (11 patients); group 2, standard prognosis [13 patients in first complete remission (CR)]. All patients engrafted on leukocytes (median day for recovery to 10(9)/L: day 30), patients with ALL recovered faster than patients with ANL (median day 19 v 34). Similarly, recovery of platelets to 50.10(9)/L occurred sooner in patients with ALL (median day 67, range day 23 through 90) whereas three patients with acute nonlymphoblastic leukemia (ANLL) in group 2 had to be supported with platelet transfusions for more than one year. In group 1, six patients had recurrent tumor within six months; three patients died from toxicity with no evidence of tumor. Two patients are still disease-free with a short follow-up (nine and ten months). In group 2, two patients died from toxicity with no evidence of leukemia three and 16 months post-ABMT. One patient with a M5 ANLL and one patient with ALL relapsed at six and 15 months, respectively. Nine patients have remained in CR or are disease-free with a median follow-up of 22 months.(ABSTRACT TRUNCATED AT 400 WORDS)