Second Malignancies and Richter's Syndrome in Patients with Chronic Lymphocytic Leukemia

Abstract

Second malignancies are frequent complications in patients with chronic lymphocytic leukemia (CLL). Patients with this leukemia may develop large cell lymphoma (LCL) known as Richter's syndrome (RS). RS occurs in CLL patients of about 3% and may develop in a single lymph node or more often in a group of nodes. However, in some patients extranodal localization of aggressive lymphoma in RS has been observed. Besides LCL, Hodgkin's disease, prolymphocytoid leukemia, multiple myeloma and acute lymphoblastic leukemia may also occur as RS variants. The origin of lymphoid cells in RS remains tentative. However, CLL and RS originate from the same clone for some patients, whereas, in other patients cells of aggressive lymphoma do not have the features of the same clone as the CLL cells. The prognosis of RS is poor. Survival in different studies will be usually 2-5 months. The secondary development or coexistence of myeloproliferative disorders or myelodysplastic syndrome and solid tumors have also been rarely documented in CLL patients. It is of great concern that therapy may further increase the risk of a second neoplasm. However, until now, there are no clear evidence that alkylating agents or purine nucleoside analogs may be associated with an increased incidence of second malignancies in patients with CLL. In this review, epidemiology, biology, clinical characteristic and treatment approaches in RS and other secondary neoplasms in patients with CLL are discussed.

Effect of Rapamycin on Mouse Chronic Lymphocytic Leukemia and the Development of Nonhematopoietic Malignancies in Eμ-TCL1 Transgenic Mice

“…Two of four malignancies were histiocytic sarcoma, a cancer of the macrophagic line known to be rare (2-5%) in 23-month-old mice (22), whereas in El-TCL1 mice was present in 18% (2 of 11) of the animals at 11 to 12 months of age. Secondary malignancies are also frequent complications in patients with CLL (23). Although the most frequent events are secondary lymphoid malignancies, solid tumors were also documented in CLL patients.…”

Use of white blood cell growth factors and risk of acute myeloid leukemia or myelodysplastic syndrome among elderly patients with non‐Hodgkin lymphoma

“…31 These agents incorporate themselves into the DNA, leading to DNA damage and interference with repair pathways. [31][32][33][34][35][36] Therefore, it is plausible that antimetabolites might interact synergistically with the proliferative and/or antiapoptotic activity of CSFs to initiate and then facilitate leukemogenesis.…”

Concomitant presentation of acute myeloid leukemia with T-cell large granular lymphocytic leukemia

“…There is a general consensus that in secondary AML, chemotherapy specific for this leukemia should be proposed only for patients with favorable karyotypes, younger age, and good performance status [10,17]. Our patient responded well to combination AML chemotherapy.…”

“…Chemotherapy of secondary AML or MDS is associated with poor results [10,17], although, Mateu et al report a case of simultaneous B-cell CLL and AML successfully treated with AMLspecific induction chemotherapy [6]. There is a general consensus that in secondary AML, chemotherapy specific for this leukemia should be proposed only for patients with favorable karyotypes, younger age, and good performance status [10,17].…”

“…The simultaneous or sequential occurrence of CLL/SLL with AML or myelodysplastic syndromes (MDS) may represent either divergent differentiation of the same stem cell clone or two separate processes [14]. It is presumed that the possible mechanism for development of AML in CLL/SLL patients includes immunodeficiency states, since patients with immunodeficiency states have higher incidence of neoplasia when compared to the general population [10]. In most cases however, AML arises after chemotherapy or radiation therapy given to treat CLL/SLL.…”