*6.9.2 Treatment and prognosis*

Hairy cell leukemia follows an indolent course and is sensitive to "gentle" chemotherapeutic regimens, which produce longlasting remissions. BRAF inhibitors appear to produce excellent responses in tumors that have failed conventional chemotherapy. The overall prognosis is excellent [1, 25].

### **6.10 Plasma cell neoplasms and related disorders**

These B-cell proliferations contain neoplastic plasma cells that virtually always secrete a monoclonal Ig or Ig fragment. These plasma cell neoplasms are also termed as plasma cell dyscrasias. Multiple myeloma is associated with frequent rearrangements involving the IgH locus and various proto-oncogenes. Included among the loci that are recurrently involved in translocations with the Ig heavy-chain gene on chromosome 14q32 are the cell cycle-regulatory genes cyclin D1 on chromosome 11q13 and cyclin D3 on chromosome 6p21. Deletions of chromosome 17p that involve the TP53 tumor suppressor locus also occur and are associated with a poor outcome. Late-stage, highly aggressive forms of the disease such as plasma cell leukemia are associated with the acquisition of rearrangements involving MYC. More recent deep sequencing of myeloma genomes has identified frequent mutations involving components of the nuclear factor κ B (NF-κB) pathway, which supports B-cell survival. Based on these studies, it is evident that myeloma is molecularly heterogeneous [1, 67].

The various spectrum of plasma cell dyscrasias are [68]: **Non-IgM monoclonal gammopathy of undetermined significance**

Serum monoclonal protein (non-IgM type) <30 g/dl. Clonal bone marrow plasma cells <10%.

The absence of end-organ damage such as hypercalcemia, renal insufficiency, anemia, and bone lesions (CRAB) or amyloidosis that can be attributed to the plasma cell proliferative disorder.

#### **IgM monoclonal gammopathy of undetermined significance**

Serum IgM monoclonal protein <30 g/dl. Bone marrow lymphoplasmacytic infiltration <10%.

No evidence of anemia, constitutional symptoms, hyperviscosity, lymphadenopathy, hepatosplenomegaly, or other end-organ damage that can be attributed to the underlying lymphoproliferative disorder.
