OBJECTIVETo explore the deletion rate, clinical correlation and prognostic significance of 1p21 deletion, a novel genetic prognostic index, in patients with multiple myeloma (MM).

METHODSThe interphase fluorescence in situ hybridization (I-FISH) was performed on purified CD138⁺ plasma cells from 78 newly diagnosed patients from Sep 2007 to Sep 2012 receiving thalidomide-based chemotherapy by using BAC probe covered 1p21.2 region that contains the human cell division cycle 14A (HCDC14A) gene. Deletion rate, the cell percentage of deletion, clinical relevance and prognostic significance were analyzed in myeloma patients.

RESULTSAmong 78 patients, there were 51 males and 27 females, the median age was 59(42-81). The deletion rate of 1p21.2 was 23.1%. Some patients had amplification (amp) of 1p with amp rate of 5.1% in 1p21.2, the amp rate was significantly lower than the deletion rate (P=0.001). 1p21.2 deletion was positively correlated with renal lesion (Cr≥177 μmol/L), high percentage of plasma cells in bone marrow, high LDH (≥220 U/L) and high β2-MG (P=0.014, 0.000, 0.010 and 0.022, respectively). With a median follow-up time of 15.0(1.0-53.5) months, the estimated median progressionfree survival (PFS) and overall survival (OS) time for patients with 1p21 deletion was (12.0±2.7) and (14.0±3.4) months, however those were (30.0±8.0) and (38.5±1.8) months in patients without 1p21 deletion, respectively (P=0.000). On multivariate analysis, which included complex karyotype, LDH≥220 U/L, renal lesion and del(17p13), 1p21 deletion remained as an independent risk factor for PFS (HR: 3.312, 95% CI: 1.095-10.017, P=0.034) and OS (HR: 4.961, 95% CI: 1.487-16.552, P=0.009).

CONCLUSION1p21 deletion is an important genetic prognosis indicator in multiple myeloma patients.

Chromosome Deletion ; Chromosomes, Human, Pair 1 ; Female ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Multiple Myeloma ; diagnosis ; drug therapy ; genetics ; Prognosis ; Thalidomide ; therapeutic use

Involvement of the central nervous system is very uncommon in multiple myeloma, observed in approximately 1% of the multiple myeloma patients. We report a case of central nervous system myelomatosis with complex chromosome aberrations in a 62-yr-old female patient, who had previously been diagnosed as multiple myeloma. Fluorescent in situ hybridization revealed 13q deletion, p53 gene deletion and IGH/FGFR3 rearrangement and chromosomal study showed complex chromosome aberrations. After four cycles of chemotherapy, the patient was admitted to the hematology department with severe headache. Plasma cells were found in the cerebrospinal fluid (CSF), and CSF immunoelectrophoresis revealed abnormal precipitin arcs against anti-IgG and anti-lambda antisera. She was given systemic chemotherapy and eight courses of intrathecal chemotherapy, which cleared plasma cells in the CSF. Two months later, she was given autologous stem cell transplantation. Three months after stem cell transplantation, central nervous system myelomatosis progressed to plasma cell leukemia and two months later,the patient expired.
Antineoplastic Agents/therapeutic use ; Central Nervous System Neoplasms/*diagnosis/drug therapy/genetics ; Cerebrospinal Fluid/cytology ; *Chromosome Deletion ; Combined Modality Therapy ; Disease Progression ; Female ; Gene Deletion ; Humans ; Immunoelectrophoresis ; In Situ Hybridization, Fluorescence ; Leukemia, Plasma Cell/diagnosis ; Middle Aged ; Multiple Myeloma/*diagnosis/drug therapy/genetics ; Plasma Cells/pathology ; Precipitins/metabolism ; Receptor, Fibroblast Growth Factor, Type 3/genetics ; Stem Cell Transplantation ; *Translocation, Genetic ; Transplantation, Autologous ; Tumor Suppressor Protein p53/genetics

No abstract available.
Aged ; Antineoplastic Agents/therapeutic use ; Bone Marrow/pathology ; Fusion Proteins, bcr-abl/genetics/metabolism ; Humans ; Imatinib Mesylate/therapeutic use ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/complications/*diagnosis/drug therapy ; Leukocyte Count ; Male ; Multiple Myeloma/complications/*diagnosis/drug therapy ; Platelet Count ; Polymerase Chain Reaction ; Thrombocytosis/etiology

OBJECTIVETo determine the incidence and clinical significance of chromosome 13q14 deletion in multiple myeloma (MM).

METHODSBone marrow samples were collected from 132 newly diagnosed MM patients referred to our hospital. Interphase fluorescence in situ hybridization (i-FISH) combined with magnetic activated cell sorting (MACS) were performed on chromosome 13q14 (RB-1).

RESULTS(1) i-FISH was used to investigate CD138-enriched bone marrow MM cells and revealed a 13q14 deletion rate of 51.5% (68/132), while conventional cytogenetic (CC) analysis revealed 13q deletions/monosomy 13 (Δ13) only of 5.0%(6/120). (2) Univariate analysis showed that 13q14 deletion rate by i-FISH > 25%, bone marrow plasma cells > 50%, ISS stage and β(2)-MG ≥ 5.5 mg/L were associated with shorter overall survival (OS). Multivariate analysis revealed that 13q14 deletion rate by i-FISH > 25% was an independent unfavorable factor (P = 0.042). (3) Patients treated with bortezomib had a much better response than those treated with traditional chemotherapy (P = 0.001). There was no significant difference in OS between patients received bortezomib with and without 13q14 deletion (P > 0.05), indicating that bortezomib could reverse the poor prognosis of 13q14 deletion.

CONCLUSION(1) i-FISH followed CD138 cell sorting appears to be a highly sensitive method for detecting 13q14 deletion. (2) 13q14 deletion rate by i-FISH > 25% is an independent unfavorable factor. (3) Bortezomib could reverse the poor prognosis of 13q14 deletion.

Adult ; Aged ; Aged, 80 and over ; Antineoplastic Agents ; therapeutic use ; Boronic Acids ; therapeutic use ; Bortezomib ; Chromosome Deletion ; Chromosome Disorders ; Chromosomes, Human, Pair 13 ; Female ; Flow Cytometry ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Middle Aged ; Multiple Myeloma ; diagnosis ; drug therapy ; genetics ; pathology ; Prognosis ; Pyrazines ; therapeutic use