Treatment of indolent lymphomas from watch and wait to high dose therapy.

Indolent B-cell non-Hodgkin’s lymphomas (IBCNHL) represent a heterogenous group of chronic diseases [1]. Follicular lymphomas grades 1 and 2 (FL1/2) are by far the most common, accounting for approximately 20% of all NHL worldwide. Indolent IBC-NHL also include small lymphocytic lymphoma (SLL), which is the tissue counterpart of B-chronic lymphocytic leukemia (B-CLL); [2], lymphoplasmacytic lymphoma (LPL; 1%), mantle cell lymphoma (MCL; 6%), and marginal zone lymphomas, either splenic (SMZL; 1%), nodal (NMZL, 2%) or extranodal MALT (8%). Various treatment strategies ranging from ‘‘watch and wait’’ policies or oral alkylating agent monotherapy to more aggressive combination chemotherapy (CT), chemoimmunotherapy or even CT followed by high dose therapy and autologous stem cell transplantation (ASCT) have been used in previously untreated patients with IBC-NHL. However there is no clear evidence for the superiority of any particular approach in terms of overall survival (OS), because: (i) The natural history of IBC-NHL is generally prolonged and many of these approaches are ultimately integrated in the overall treatment strategy, thus minimizing OS differences, despite significant differences in progression free survival (PFS); (ii) With the exception of FL, the rarity of these disorders raises further difficulties in the design of randomized trials. We will review here current treatment approaches for FL1/2, MCL, SLL, LPL including Waldenstrom’s macroglobulinemia and NMZL, SMZL and extranodal MZ lymphomas of MALT type (EMZL), focusing mainly on first-line therapies.