Abstract
Aim
In order to assess the influence of total-body irradiation (TBI) on the outcome and incidence of complication after bone marrow transplantation (BMT), we retrospectively analyzed our patients treated for acute leukemia and conditioned with TBI prior to BMT.
Patients and Methods
Between 1980 and 1993, 326 patients referred to our department with acute non-lymphoblastic leukemia (ANLL, n=182) and acute lymphoblastic leukemia (ALL, n=144) in complete remission underwent TBI either in single dose (190 patients: 10 Gy administered to the midplane, and 8 Gy to the lungs [STBI]) or in 6 fractions (136 patients: 12 Gy on 3 consecutive days, and 9 Gy to the lungs [FTBI]) before BMT. The male-to-female ratio was 204/122 (1.67), and the median age was 30 years (mean: 30 ± 11, range: 3 to 63). The patients were analyzed according to 3 instantaneous dose rate groups: 118 patients in the LOW group (≤0.048 Gy/min), 188 in the MEDIUM group (> 0.048 and ≤ 0.09 Gy/min), and 20 in the HIGH group (> 0.09 cGy/min). Conditioning chemotherapy consisted of cyclophosphamide (CY) alone in 250 patients, CY and other drugs in 54, and 22 patients were conditioned using combinations without CY. Following TBI, allogeneic and autologous BMT were realized respectively in 118 and 208 patients. Median follow-up period was 68 months (mean: 67 ± 29, range: 24 to 130 months).
Results
Five-year survival, LFS, RI and TRM rates were 42%, 40%, 47%, and 24%, respectively. Five-year LFS was 36% in the STBI and 45% in the FTBI group (p = 0.17). It was 36% in the LOW group, 42% in the MEDIUM group, and 30% in the HIGH group (p > 0.05). Five-year RI was 50% in STBI, 43% in FTBI, 55% in LOW, 41% in MEDIUM, and 44% in HIGH groups (STBI vs. FTBI, p = 0.48; LOW vs. MEDIUM, p = 0.03: MEDIUM vs. HIGH, p = 0.68). TRM was not influenced significantly by the different TBI techniques. When analyzing separately the influence of fractionation and the instantaneous dose rate either in ANLL or ALL patients, no difference in terms of survival and LFS was observed. Fractionation did not influence the 5-year RI both in ANLL and ALL patients. However, among the patients with ANLL, 5-year RI was significantly higher (58%) in the LOW group than the MEDIUM group (31%, p = 0.001), whereas instantaneous dose rate did not significantly influence the RI in ALL patients. The 5-year TRM rate was significantly higher in allogeneic BMT group both in ANLL (37%) and ALL (37%) patients than those treated by autologous BMT (ANLL: 15%, ALL: 18%: p = 0.002 and 0.02, respectively). The 5-year estimated interstitial pneumonitis (IP) and cataract incidence rates were 22% and 19%, respectively, in all patients. IP incidence seemed to be higher in the HIGH group (46%) than the MEDIUM (19%, p = 0.05) or LOW (25%, p = 0.15) groups. Furthermore, cataract incidence was significantly influenced by fractionation (STBI vs. FTBI, 29% vs. 9%; p = 0.003) and instantaneous dose rate (LOW vs. MEDIUM vs. HIGH, 0% vs. 27% vs. 33%; p < 0.0001). Multivariate analyses revealed that the best factors influencing the survival were 1st CR (p = 0.0007), age ≤ 40 years (p = 0.003), and BMT after 1985 (p = 0.008). The RI was influenced independently only by the remission status (p = 0.0002). On the other hand, the TRM rate was lower in patients who did not experience graft-vs.-host disease (GvHD, p < 0.0001), and in those treated after 1985 (p = 0.0005). GvHD was the only independent factor involved in the development of IP (p = 0.01). When considering the cataract incidence, the only independent factor was the instantaneous dose rate (p = 0.0008).
Conclusion
The outcome of BMT patients conditioned with TBI for acute leukemia was not significantly influenced by the TBI technique, and TRM seemed to be lower in patients treated after 1985. On the other hand, cataract incidence was significantly influenced by the instantaneous dose rate.
Zusammenfassung
Hintergrund
Um den Einfluß der Ganzkörperbestrahlung (TBI) auf die Prognose und die Inzidenz von Komplikationen bei Knochenmarktransplantationen (BMT) zu evaluieren, haben wir retrospektiv unser Patientengut, das bei akuter Leukämie vor der BMT mit der TBI behandelt wurde, analysiert.
Patienten und Methode
Von 1980 bis 1993 wurden 326 Patienten mit akuter nichtlymphatischer Leukämie (ANLL, n = 182) und akuter lymphatischer Leukämie (ALL, n = 144) in Vollremission in unserer Abteilung mit einer TBI vor einer BMT behandelt. Die TBI wurde entweder mit einer Einzeldosis (STBI; n = 190: 10 Gy L4, 8 Gy Lungen) oder in sechs Fraktionen (FTBI; n = 136: an drei aufeinanderfolgenden Tagen 12 Gy L4, 9 Gy Lungen) appliziert. Die Männer/Frauen-Ratio betrug 204/122 (1,67). und das mediane Alter betrug 30 Jahre (± 11, 3–63). Außerdem wurden die Patienten in Relation zu drei momentanen Dosisraten analysiert: 118 Patienten waren in der Gruppe mit niedriger Dosisrate (LDR; ≤ 0,048 Gy/min), 188 wurden mit mittlerer Dosisrate (MDR; > 0,048 und ≤ 0.09 Gy/min) und 20 mit einer hohen Dosisrate (HDR; > 0,09 Gy/min) bestrahlt. Die konditionierende Chemotherapie bestand aus Cyclophosphamid (CY) alleine bei 250 Patienten, CY und anderen Medikamenten bei 54 Patienten, und 22 Patienten wurden mit Kombinationen ohne CY behandelt. Nach der TBI wurden allogene und autologe BMT bei respektive 118 und 208 Patienten durchgeführt. Das mediane Follow-up betrug 68 Monate (67 ± 29,24 bis 130 Monate).
Ergebnisse
Das Fünf-Jahres-Überleben, das leukämiefreie Überleben (LFS), die Fünf-Jahres-Rezidivinzidenz (RI) und die therapiebedingte Mortalität (TRM) betrugen jeweils 42%, 40%, 47% und 24%. Das LFS betrug 36% in der STBI- und 45% in der FTBI-Gruppe (p = 0,17). Es betrug 36% in der LDR-, 42% in der MDR- und 30% in der HDR-Gruppe (p > 0,05). Die RI betrug 50% in der STBI-, 43% in der FTBI-, 55% in der LDR-, 41% in der MDR- und 44% in der HDR-Gruppe (STBI vs. FTBI, p = 0,48: LDR vs. MDR, p = 0,03; MDR vs. HDR, p = 0,68). Die TRM wurde durch die unterschiedlichen Bestrahlungstechniken nicht signifikant beeinflußt. Bei der getrennten Analyse des Einflusses der Fraktionierung und der momentanen Dosisrate bei ANLL- oder ALL-Patienten wurde kein Unterschied für das Überleben oder das LFS beobachtet. Die Fraktionierung beeinflußte die RI weder bei den ANLL- noch bei den ALL-Patienten. Jedoch war bei den ANLL-Patienten die RI signifikant höher (58%) in der LDR- als in der MDR-Gruppe (31%, p = 0,001), die momentane Dosisrate zeigte aber keinen signifikanten Einfluß auf die RI bei ALL-Patienten. Die Fünf-Jahres-TRM-Rate war in der allogenen BMT-Gruppe bei den ANLL- (37%) und ALL-Patienten (37%) signifikant höher als bei der autologen BMT-Gruppe (ANLL 15%, ALL 18%; respektive p = 0,002 und 0,02). Die Fünf-Jahres-Inzidenzraten für die interstitielle Pneumonitis (IP) und Katarakt betrugen 22% respektive 19% bei allen Patienten. Die IP-Inzidenz schien höher zu sein in der HDR- (46%) als in der MDR- (19%, p = 0,05) und LDR-Gruppe (25%, p = 0,15). Außerdem wurde die Kataraktinzidenz signifikant durch die Fraktionierung (STBI vs. FTBI, 29% vs. 9%, p = 0,003) und die momentane Dosisrate (LDR vs. MDR vs. HDR, 0% vs. 27% vs. 33%, p < 0,0001) beeinflußt. Multivarianzanalysen zeigten folgende Hauptfaktoren, die die Überlebensraten beeinflußten: erste Vollremission (p = 0,0007). Alter < 40 Jahre (p = 0,003) und BMT nach 1985 (p = 0,008). Die RI wurde unabhängig nur durch den Remissionsstatus beeinflußt. Außerdem war die TRM-Rate niedriger bei Patienten, die keine Graft-vs.-Host-Reaktion (GvHD, p < 0,0001) hatten, und bei den Patienten, die nach 1985 behandelt wurden. GvHD war der einzige unabhängige Faktor in der Entwicklung der IP (p = 0,01). Für die Kataraktinzidenz fand sich als einziger unabhängiger Faktor die momentane Dosisrate (p = 0,0008).
Schlußfolgerungen
Die Prognose der BMT-Patienten, die mit einer TBI bei akuter Leukämie behandelt wurden, wurde nicht durch die TBI-Technik signifikant beeinflußt, und die TRM schien bei den Patienten, die nach 1985 behandelt wurden, niedriger auszufallen. Außerdem wurde die Kataraktinzidenz durch die momentane Dosisrate signifikant beeinflußt.
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Belkacémi, Y., Pène, F., Touboul, E. et al. Total-body irradiation before bone marrow transplantation for acute leukemia in first or second complete remission. Strahlenther Onkol 174, 92–104 (1998). https://doi.org/10.1007/BF03038482
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DOI: https://doi.org/10.1007/BF03038482