Radiation Therapy in Precursor T-Lymphoblastic Lymphoma/Leukemia

Abstract

T-cell acute lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) are a biological unit in the World Health Organization classification, called “T-precursor lymphoblastic leukemia/lymphoma.” T-ALL and T-LBL are held to be the same disease with a difference in the extent of bone marrow infiltration, having a cut point of 25%. These T-cell malignancies are rare diseases. In adults, T-LBL represents a low incidence of <2% of all non-Hodgkin lymphomas (NHLs). Both entities are aggressive and show a similar incidence of initial involvement of the central nervous system (CNS), but are curable in adult patients. The major clinical difference is the higher frequency of mediastinal tumors in T-LBL. The mediastinum remains the typical site of relapse. Clinical symptoms related to the disease might be painless enlarged lymph nodes, superior vena cava syndrome, and constitutional B symptoms. The primary diagnostic workup includes the typical medical examinations as in other NHL, inclusively total-body CT-scan, cerebrospinal fluid examination, and bone marrow biopsy. The 18F-FDG–PET has proven to be relevant for response evaluation. The role of surgery is undefined and should be discussed multidisciplinary. Typical systemic NHL regimens used in the past like CHOP, consisting of a combination of cyclophosphamide, doxorubicin, vincristine, and prednisone, or CHOP-like chemotherapies showed response rates in adults ranging from 55% to 95% and survival rates of 30–50%, even in combination with CNS prophylaxis and radiotherapy. Pediatric-inspired ALL treatment regimes, as the protocols of the GMALL or of the GRAALL study group, have shown significantly improved complete remission rates of 76–93% and have prolonged event-/progression-free survival of 62–76% after 3–8 years and overall survival of up to 65–69% after 3–5 years in adult LBL patients. For patients with relapsed T-ALL, allogeneic HSCT may represent the best chance for long-term survival.

Indications for radiotherapy are cranial irradiation (prophylaxis or when CNS is involved) and mediastinal irradiation as well as within a conditioning scheme before allo-HSCT. The use of intrathecal chemotherapy, methotrexate (MTX) or triple therapy (MTX, Ara-C, corticosteroids), cranial irradiation, or a combination of cranial irradiation and intracranial chemotherapy are common CNS therapies. CNS prophylaxis, including intrathecal and systemic chemotherapy and CNS irradiation, reduces significantly the risk of CNS relapse. Referring to the GMALL treatment protocol 07/2003, a combination of intrathecal chemotherapy, high-dose methotrexate, and cytarabin treatment as well as 24 Gy whole-brain cranial irradiation leads to less than 2% of CNS relapses. CNS prophylaxis should be administered early during induction phase II for avoiding CNS relapses.

Mediastinal irradiation in certain patient groups of T-LBL may improve treatment outcome. Future studies have to evaluate which patients will likely benefit from mediastinal irradiation.

The GMALL-08/2013 protocol on T-LBL suggests conditioning therapy prior allogeneic HSCT with radiation-based conditioning: TBI-dose of 12 Gy with 2 Gy per fraction and two fractions daily in younger patients. For older patients over the age of 45 years, the TBI-dose should be reduced to 8 Gy (2 Gy per fraction and two fractions daily).