Page 1571 - Hematology_ Basic Principles and Practice ( PDFDrive )

1398 Part VII Hematologic Malignancies

affected the 4-year estimate of progression-free survival (PFS) (≥3 such as bone marrow MVD, serum soluble syndecan-1 levels, soluble
FLs, 50%; SUV >4.2, 43%; presence of EMD, 28%). An SUV >4.2 CD16 levels, and bone marrow pDC numbers; patient-related
and EMD was also correlated with a shorter OS (4-year OS rates factors, such as age, renal failure, albumin, and performance status;
77% and 66%, respectively). In this study, posttherapy persistence of and treatment-related factors, such as achieving a CR or a very good
PET positivity for lesions predicted a poor outcome as compared with partial response (VGPR) and the performance of tandem autologous
those with a negative PET-CT (PFS 66% and OS 89%). transplants. Among these features, the International Staging System
A prospective evaluation of MRI and PET-CT at diagnosis and (ISS) uses serum albumin and β 2-microglobulin levels, cytogenetic/
before maintenance therapy was performed in a subgroup of 134 FISH changes, and newer genomic correlates of outcome that have
patients with MM in the IFM/DFCI 2009 trial. At diagnosis, MRI been validated in a number of studies and are considered standard
was positive in 127 (94.7%) of 134 patients and PET-CT was positive predictive markers. A short list of investigations to be performed for
in 122 (91%) of 134 patients, respectively (p = .33). Few patients risk stratification of patients with MM is provided in Table 86.10. 21
achieved a normal MRI after three cycles of VRD before maintenance.
Normalization of the MRI following three cycles of VRD and before
maintenance had no prognostic value for both PFS and OS. Normal- INTERNATIONAL STAGING SYSTEM
ization of PET-CT was more frequently observed: 45% following three
cycles of VRD and 79% before maintenance. Importantly, normaliza- The ISS described in Table 86.11 uses simple chemical tests (serum
22
tion of PET-CT was associated with an improvement in PFS, and albumin and β 2-microglobulin) to predict outcome. ISS staging is
normalization before maintenance was a predictor for improved OS.

TABLE
Renal Function 86.10 Risk Stratification in Multiple Myeloma
A serum creatinine >173 mmol/L is considered to represent end- Investigations Recommended for Risk Stratification
organ damage. Because absolute creatinine values do not incorporate Serum albumin and β 2 -microglobulin to determine ISS stage
the patient’s age, they may underrepresent the extent of renal dysfunc- Bone marrow examination for t(4;14), t(14;16), and del(17p) on
tion. There has been consideration of using the creatinine clearance identified PCs by FISH
as a more optimal diagnostic criterion. Because patients with myeloma LDH
are older and other comorbidities such as diabetes and hypertension Immunoglobulin type: IgA
can also affect renal function, it is necessary to establish the relation- Histology: plasmablastic disease or plasma cell leukemia
ship between renal dysfunction and the plasma cell disorder; for Additional Investigations for Risk Stratification
example, the presence of Bence Jones proteinuria may be required to
support such a relationship. In the absence of Bence Jones proteinuria, Cytogenetics
a renal biopsy may be necessary. This may be even more critical in Gene expression profiling
patients who otherwise fit the criteria for MGUS or SMM but have Labeling index
renal dysfunction. A renal biopsy is not required for all patients, but MRI/PET scan
only when one is uncertain about the cause of the renal dysfunction. DNA copy number alteration by CGH/SNP array
A biopsy is not currently required to document light chain cast CGH/SNP, Comparative genomic hybridization/single-nucleotide polymorphism;
nephropathy if Bence Jones protein is present as the predominant FISH, fluorescence in situ hybridization; IgA, immunoglobulin A; ISS,
urinary protein. Other causes of renal dysfunction should be consid- International Staging System; LDH, lactate dehydrogenase; MRI, magnetic
ered before attributing renal dysfunction to MM. resonance imaging; PET, positron emission tomography.

Hemogram and Serum Calcium TABLE Standard Risk Factors for Multiple Myeloma and the
86.11 Revised International Staging System
A standard complete blood count is performed to detect anemia. The
level of anemia considered diagnostic of myeloma is a hemoglobin Prognostic Factor Criteria
2 g/dL below the lower limit of normal or the patient’s baseline level ISS stage
or hemoglobin <10 g/dL. It is always necessary to exclude other I Serum β 2 -microglobulin <3.5 mg/L, serum
causes of anemia. Circulating plasma cells are frequently observed in albumin ≥3.5 g/dL
patients with MM. A serum calcium level should be measured and II Not ISS stage I or III
corrected to the level of albumin, or in occasional cases, an ionized III Serum β 2 -microglobulin ≥5.5 mg/L
calcium level should be obtained.
CA by iFISH
High risk Presence of del(17p) and/or translocation t(4;14)
Prognosis and/or translocation t(14;16)
Standard risk No high-risk CA
Myeloma is a disease with a varied outcome, with 20% of patients LDH
having a survival of less than 2 years, whereas over 40% of patients Normal Serum LDH below the upper limit of normal
have more than a 10-year survival. Therefore it is critically important High Serum LDH above the upper limit of normal
to identify disease features that allow one to identify low- versus A New Model for Risk Stratification for MM R-ISS stage
high-risk disease to better tailor therapeutic interventions. Moreover, I ISS stage I and standard-risk CA by iFISH and
such a risk stratification approach permits the physician to predict normal LDH
life expectancy and allows one to develop metrics by which to evaluate II Not R-ISS stage I or III
the results of clinical trials. Various prognostic variables have been III ISS stage III and either high-risk CA by iFISH or
identified, including tumor-burden related factors such as β 2- high LDH
microglobulin, more than three lytic bone lesions, hypercalcemia, CA, Chromosomal abnormalities; iFISH, interphase fluorescence in situ
and soluble IL-6 receptor; tumor biology–related factors such as hybridization; ISS, International Staging System; LDH, lactate dehydrogenase;
cytogenetic/FISH-identified abnormalities, genomic changes, plasma MM, multiple myeloma; R-ISS, revised International Staging System.
cell labeling index, IgA myeloma, C-reactive protein, and lactate From Greipp PR, San Miguel J, Durie BG, et al: International staging system for
multiple myeloma. J Clin Oncol 23:3412, 2005.
dehydrogenase (LDH); tumor microenvironment–related factors,