This chapter reviews the different levels of remission used to define depth of response in myeloma and their clinical significance, as well as the prognostic value and unique characteristics of minimal residual disease detection. Summary points Assessment of minimal residual disease (MRD) is becoming standard diagnostic care for potentially curable neoplasms such as some acute leukemias as well as chronic myeloid and lymphocytic leukemia. Multiple myeloma (MM) remains an incurable disease and no clinical trial has randomized MM patients according to their MRD status in order to investigate the role of MRD to individualize therapy. The experience of several cooperative groups using different MRD techniques has indicated that persistence of MRD is always an adverse prognostic feature. It is thus recommended that it would be safer to take clinical decisions based on MRD-positivity rather than on MRD-negativity, since the patchy pattern of bone marrow (BM) infiltration typically observed in MM leads to a degree of uncertainty regarding MRD-negative results: does this guarantee absence of tumor cells or is it the result of a non-representative BM sample due to patchy tumor infiltration? Many studies have shown the value of MRD to evaluate the efficacy of specific treatment phases and therefore to support potential treatment decisions. Several groups have confirmed the added value of MRD in MM, and the time has come to establish the role of baseline risk factors plus MRD monitoring for tailored therapy. This requires the introduction of standardized, highly sensitive, cost-effective, and broadly available MRD techniques in clinical trials. The choice of MRD technology for monitoring will depend on how individual centers’ priorities adjust to the specific advantages that each tool has to offer. Paiva B, García-Sanz R, & San Miguel JF. In:  Plasma Cell Dyscrasias . Edited by Roccaro AM & Ghobrial IM. Springer International Publishing, 2016. doi:10.1007/978-3-319-40320-5_7

In this chapter, Manier et al. describe the 'driver' gene alterations involved in the development and progression of multiple myeloma (MM) and discuss the therapeutic implications of a comprehensive understanding of the genomic complexity of MM. Summary points The pathologic diagnosis of multiple myeloma (MM) and other plasma cell proliferative disorders (PCPD) is made on the bone marrow aspirate and biopsy specimen. The goal of the pathologic examination of the bone marrow is to: (a) quantify bone marrow plasma cells (PC); (b) establish PC clonality; (c) distinguish MM from lymphoplasmacytic lymphoma (LPL) and other B-cell lymphomas with plasmacytic differentiation; (d) analyze prognostic factors; (e) detect amyloid deposits; and (f) detect other potential pathologic processes. The standard of care for PC quantification is still morphologic assessment of the bone marrow aspirate and biopsy. Clonality of PCs is inferred by showing of monotypic immunoglobulin light chain expression (kappa or lambda) and/or abnormal patterns of antigen expression. Bone marrow examination helps differentiate LPL from MM. In MM, a monomorphic PC population is usually pure without associated lymphoid component, whereas in LPL small lymphocytes and plasmacytoid lymphocytes typically predominate. The most important laboratory prognostic factors are proliferation rate of neoplastic plasma cells and cytogenetic findings. Amyloid accumulation in extracellular space leads to multiple organ dysfunction; amyloid deposits can be detected in the tissue biopsy using Congo Red stain under polarized light. There is a wide range of pathologic processes that can accompany PCPDs. The most common ones are large granular lymphocyte proliferations and therapy-related myeloid neoplasms. Jevremovic D & Morice W. In: Multiple Myeloma . Edited by Gertz MA & Rajkumar SV. Springer New York, 2014. doi:10.1007/978-1-4614-8520-9_3

Hereditary syndromes with a propensity to develop AML or other myeloid neoplasms are proposed to form a distinct category [2].

A review of the benefits and risks of tyrosine kinase inhibitor treatment for patients with chronic myeloid leukemia and discussion of when to use these agents in different treatment settings. Nat Rev Clin Oncol  2017;14: 141–154. doi:10.1038/nrclinonc.2016.139

Infiltration of extramedullary organs by leukemic blasts is found in 2.5–9% of acute myeloid leukemia (AML) patients.

Chemotherapy-related myeloid neoplasms constitute up to 20% of all acute myeloid leukaemias and myelodysplastic syndromes (Morton et al , 2013).

Coombs et al discuss the importance of integrating mutational data into treatment decisions for patients with acute myeloid leukemia and propose novel therapeutic algorithms in the era of molecular medicine. Nat Rev Clin Oncol  2016; 13: 305–318. doi:10.1038/nrclinonc.2015.210

ETP-ALL is an immature stem or progenitor cell leukaemia characterized by expression of cytoplasmic CD3 but reduced or absent expression of several T-cell markers (CD1a, CD8 and CD5) and aberrant expression of myeloid or stem cell markers. 116 Many studies have shown that patients with ETP-ALL have poor outcomes, 116, 117, 118 although this is partly mitigated in later studies. 119, 120 Genome sequencing has shown that ETP-ALL is a genetically heterogeneous disease, which despite a distinct gene-expression profile, lacks a common chromosomal rearrangement or translocation. 19 Several pathways are recurrently mutated by multiple mechanisms in ETP-ALL.

VHL disease is an autosomal-dominant hereditary cancer syndrome that predisposes affected individuals to a variety of benign and malignant neoplasms including ccRCC.