Hertenstein B, Wiesneth M, Novotny J, Bunjes D, Stefanic M, Heinze B, Hübner G, Heimpel H, Arnold R
Department of Internal Medicine III, University of Ulm, Germany.
Transplantation. 1993 Nov;56(5):1114-8. doi: 10.1097/00007890-199311000-00013.
Eight patients with chronic myeloid leukemia relapse after allogeneic BMT were treated with IFN-alpha and buffy coat transfusions (BC) of the bone marrow donor. The antileukemic effect of this treatment was directly demonstrated in 4 patients by the disappearance of Philadelphia chromosome-positive metaphases or the loss of detectable BCR-ABL transcripts by polymerase chain reaction. In 2 patients in whom cytogenetic or polymerase chain reaction analysis was not performed, a change in hemopoietic chimerism with recurrence of donor-type hemopoiesis was demonstrated. Two patients, both treated in advanced stages of hematological relapse after BMT, did not respond. However, severe side effects of the treatment were observed: graft-versus-host disease (GVHD) occurred in 5 patients. Two of these patients progressed to severe chronic GVHD and 1 patient ultimately died of this complication. GVHD occurred in 5 of the 6 responding patients; one patient responded without developing clinical symptoms of GVHD. Six patients developed bone marrow hypoplasia after IFN/BC treatment, and pancytopenia occurred in 4 patients. None of these 4 patients recovered spontaneously and 2 patients died of complications of pancytopenia (cerebral bleeding, infection). Our results demonstrate that treatment of chronic myeloid leukemia relapse with IFN and BC transfusions is highly effective in patients with relapse in chronic phase. The occurrence of GVHD and pancytopenia, however, resulted in a high treatment-associated morbidity and mortality. Whereas a response to treatment was observed in 1 patient without GVHD, indicating that GVHD and a graft-versus-leukemia effect may be clinically separable, bone marrow hypoplasia occurred in all responding patients.
8例异基因骨髓移植后慢性髓性白血病复发的患者接受了α干扰素和骨髓供体的 Buffy 血(BC)输注治疗。4例患者通过费城染色体阳性中期相消失或聚合酶链反应检测不到BCR-ABL转录本,直接证明了该治疗的抗白血病效果。2例未进行细胞遗传学或聚合酶链反应分析的患者,显示造血嵌合体发生变化,供体型造血复发。2例均在骨髓移植后血液学复发晚期接受治疗的患者无反应。然而,观察到治疗有严重副作用:5例患者发生移植物抗宿主病(GVHD)。其中2例进展为严重慢性GVHD,1例最终死于该并发症。6例有反应的患者中有5例发生GVHD;1例有反应但未出现GVHD临床症状。6例患者在干扰素/BC治疗后出现骨髓发育不全,4例患者发生全血细胞减少。这4例患者均未自发恢复,2例死于全血细胞减少并发症(脑出血、感染)。我们的结果表明,干扰素和BC输注治疗慢性髓性白血病复发对慢性期复发患者非常有效。然而,GVHD和全血细胞减少的发生导致了与治疗相关的高发病率和死亡率。1例无GVHD的患者对治疗有反应,表明GVHD和移植物抗白血病效应在临床上可能是可分离的,所有有反应的患者均出现骨髓发育不全。