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Long-term results of total body irradiation in adults with acute lymphoblastic leukemia

Langzeitergebnisse der Ganzkörperbestrahlung bei Erwachsenen mit akuter lymphatischer Leukämie

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Abstract

Purpose

The aim of this chart review of adult patients treated for acute lymphoblastic leukemia (ALL) with total body irradiation (TBI) was to evaluate early and late toxicity and long-term outcome.

Patients and methods

A total of 110 adult patients (34 ± 12 years) with ALL underwent TBI (6 fractions of  2 Gy for a total of 12 Gy) as a part of the treatment regimen before transplantation. Treatment-related toxicity, mortality, and hematologic outcome are reported.

Results

Mean follow-up was 70 months. The 2- and 5-year leukemia-free survival rates were 78 and 72 %, respectively. In all, 29 % (32/110) patients suffered from medullary recurrence after a median time of 7 months. Gender was the only statistically significant prognostic factor in terms of overall survival in favor of female patients. Treatment-related mortality and overall survival after 2 and 5 years were 16 and 22 %, and 60 and 52.7 %, respectively. The most frequent late reaction wascGVHD of the skin (n = 33, 30 %). In addition, 15.5 % (17/110 patients) suffered pulmonary symptoms, and 6 patients developed lung fibrosis. Eyes were frequently affected by the radiation (31/110 = 28 %); 12 of 110 patients (11 %) presented with symptoms from osteoporosis, 5 of 110 patients (4.5 %) developed hypothyreosis and 2 patients diabetes mellitus. Of the male patients, 11 % reported erectile dysfunction or loss of libido, while 2 of 36 women reported menopausal syndrome at the mean time of 28 months after treatment with requirement for substitution. No women became pregnant after treatment. No acute or late cardiac toxicities were documented in our patients. No secondary malignancies were documented.

Conclusion

Although hematologic outcome was in the upper range of that reported in the literature, treatment-related mortality (TRM) and medullary recurrences remain a challenge. Sophisticated radiation techniques allow for decreasing toxicity to certain organs and/or dose escalation to the bone marrow in highly selected patients in order to improve therapeutic breadth.

Zusammenfassung

Ziel

Ziel der Arbeit war die Auswertung der Akut- und Spättoxizität sowie der Therapieergebnisse erwachsener Patienten mit akuter lymphatischer Leukämie (ALL) nach Ganzkörperbestrahlung ("total body irradiation", TBI) als Teil des Therapiekonzepts.

Patienten und Methode

Im Rahmen einer retrospektiven Auswertung von 110 erwachsenen Patienten (34 ± 12 Jahre) mit ALL, die eine TBI (6-mal 2 Gy–12 Gy) vor Transplantation erhalten hatten, werden therapiebedingte Akut- und Spättoxizität, Mortalität und Therapieergebnisse dargestellt.

Ergebnisse

Die mittlere Nachbeobachtungszeit betrug 70 Monate. Die leukämiefreien 2- und 5-Jahres-Überlebensraten betragen 78 bzw. 72 %. Nach im Median 7 Monaten erlitten 29 % (32/110) der Patienten ein medulläres Rezidiv. Das Geschlecht war der einzige statistisch signifikante Faktor bezüglich des Gesamtüberlebens zugunsten der weiblichen Patienten. Die therapiebedingte Mortalitäts- und die Gesamtüberlebensraten nach 2 und 5 Jahren waren 16 und 22 %, bzw. 60 und 52,7 %. Die chronische "Graft-versus-host"-Erkrankung (cGVHD) der Haut war die häufigste Spätreaktion (n = 33, 30 %), gefolgt von 15,5 % (17/110) pulmonaler cGVHD. Eine Lungenfibroseentwickelten 6 Patienten. Ophthalmologische Symptome berichteten 28 % (31/110); 11 % der Patienten (12/110) entwickelten eine symptomatische Osteoporose, 5/110 (4,5 %) eine Hypothyreose und 2 Patienten einen Diabetes mellitus. Von den männlichen Patienten litten 11 % unter erektiler Dysfunktion oder Libidoverlust nach Therapie. Wegen menopausaler Beschwerden benötigten 2/36 Frauen nach einer mittleren Zeit von 28 Monaten nach Therapie eine Hormonersatztherapie. Keine Patientin wurde nach Therapie schwanger. Es wurde weder eine akute noch eine späte kardiale Toxizität dokumentiert, ebenso kein Sekundärmalignom.

Schlussfolgerung

Obwohl das Therapieergebnis des vorliegenden Kollektivs im oberen Bereich der Literatur einzuordnen ist, bleiben sowohl die therapiededingte Mortalität als auch die Rate an medullären Rezidiven eine Herausforderung in der Therapie der adulten ALL. Moderne Techniken erlauben es, die Toxizität in bestimmten Organen selektiv zu senken und/oder die Dosis im Knochenmark für selektionierte Patienten zu eskalieren. Hier könnten in der Zukunft Ansätze vorhanden sein, die therapeutische Breite zu verbessern.

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Acknowledgment

We thank S. Diehl (Data Bank Manager) for her support.

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Conflict of interest

The authors declare that there are no actual or potential conflicts of interest in relation to this article.

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Authors and Affiliations

  1. Department of Radiation Oncology, Charité University Medicine, Augustenburger Platz 1, 13353, Berlin, Germany

    Simone Marnitz MD, Alexander Zich, Volker Budach MD, Ulrich Jahn MPh & Oliver Neumann

  2. Department of Hematology and Oncology, Bone Marrow Transplant Unit, Charité University Medicine, Campus CVK, Berlin, Germany

    Renate Arnold

  3. Institute of Clinical Epidemiology and Applied Biostatistics, University Tübingen, Tübingen, Germany

    Peter Martus MPh

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  1. Simone Marnitz MD
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  2. Alexander Zich
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Correspondence to Simone Marnitz MD.

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Marnitz, S., Zich, A., Martus, P. et al. Long-term results of total body irradiation in adults with acute lymphoblastic leukemia. Strahlenther Onkol 190, 453–458 (2014). https://doi.org/10.1007/s00066-014-0607-3

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