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Waldenström macroglobulinemia with extramedullary involvement at initial diagnosis portends a poorer prognosis.

Cao X, Ye Q, Orlowski RZ, Wang X, Loghavi S, Tu M, Thomas SK, Shan J, Li S, Qazilbash M, Yin CC, Weber D, Miranda RN, Xu-Monette ZY, Medeiros LJ, Young KH - J Hematol Oncol (2015)

Bottom Line: Kaplan-Meier survival analysis results showed that EMWM patients had a significantly shorter median overall survival (P < 0.001) and progression-free survival (PFS) (P < 0.001) than did BMWM patients.Additionally, initial treatment with rituximab significantly improved the PFS of BMWM patients (P = 0.012) but had no effect on EMWM patients.However, EMWM patients treated with nucleoside analogs attained a better PFS than those who did not (P = 0.021).

View Article: PubMed Central - PubMed

Affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. cathyjiangsu@163.com.

ABSTRACT

Background: The prognostic importance of extramedullary involvement in patients with Waldenström macroglobulinemia (WM) at diagnosis and treatment options for these patients has not been well evaluated. In this study, we investigated the clinical manifestations, biological features, and effect of first-line therapy on the outcome of WM patients diagnosed with extramedullary involvement (EMWM) vs those with only bone marrow involvement (BMWM).

Methods: We analyzed the clinical data of 312 WM patients diagnosed with EMWM (n = 106) and BMWM (n = 206) at The University of Texas MD Anderson Cancer Center from 1994 to 2014. EMWM was confirmed by biopsy, positron emission tomography-computed tomography, or magnetic resonance imaging, and clinical laboratory analyses.

Results: Characteristics associated with EMWM were male sex (P = 0.027), age younger than 65 years (P = 0.048), presence of B symptoms (P < 0.001), high serum beta-2 macroglobulin (P < 0.001) level, low serum albumin level (P = 0.036), and cytogenetic abnormalities (P = 0.010). Kaplan-Meier survival analysis results showed that EMWM patients had a significantly shorter median overall survival (P < 0.001) and progression-free survival (PFS) (P < 0.001) than did BMWM patients. Chemotherapy combined with targeted therapy improved PFS for BMWM patients (P = 0.004) but not for EMWM patients. Additionally, initial treatment with rituximab significantly improved the PFS of BMWM patients (P = 0.012) but had no effect on EMWM patients. However, EMWM patients treated with nucleoside analogs attained a better PFS than those who did not (P = 0.021).

Conclusions: We show that extramedullary involvement at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy with nucleoside analogs improved PFS for patients with EMWM. The study provides unique clinical and treatment observations in subtypes of WM patients.

No MeSH data available.


Related in: MedlinePlus

The tissue or bone marrow involvement pattern and immunophenotypic profiling of the EMWM and BMWM patients. a, b A representative diffuse interstitial pattern of bone marrow biopsy in a patient with BMWM, ×40 and × 80 magnification. c Bone marrow aspirate smear showed many abnormal small lymphoid cells admixed with variable plasmacytoid cells and plasma cells, ×80 magnification. d CD20 stain on the abnormal small lymphoid cells, ×80 magnification. e CD138 stain on the plasmacytoid and plasma cells, ×80 magnification. f, g Immunophenotypic profiling of CD38 and CD138 positive plasmacytoid and plasma cells with strong monotypic cytoplasmic kappa light chain expression. h The abnormal small lymphoid cells were CD20 positive and showed monotypic kappa light chain expression. i, j A representative diffuse infiltrative pattern of a lymph node biopsy in a patient with EMWM, MYD88 mutation positive, ×40 and × 80 magnification. k CD20 stain on abnormal small lymphoid cells, ×80 magnification. l CD138 stain on few admixed plasmacytoid and plasma cells, ×80 magnification. m, o Immunophenotypic profiling of CD19 and CD20 positive small B-cells with kappa light chain restriction and were negative for CD5 and CD10. p Identical monotypic kappa light chain expression in the lymphoid cells was also seen in the plasmacytoid and plasma cells
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Fig2: The tissue or bone marrow involvement pattern and immunophenotypic profiling of the EMWM and BMWM patients. a, b A representative diffuse interstitial pattern of bone marrow biopsy in a patient with BMWM, ×40 and × 80 magnification. c Bone marrow aspirate smear showed many abnormal small lymphoid cells admixed with variable plasmacytoid cells and plasma cells, ×80 magnification. d CD20 stain on the abnormal small lymphoid cells, ×80 magnification. e CD138 stain on the plasmacytoid and plasma cells, ×80 magnification. f, g Immunophenotypic profiling of CD38 and CD138 positive plasmacytoid and plasma cells with strong monotypic cytoplasmic kappa light chain expression. h The abnormal small lymphoid cells were CD20 positive and showed monotypic kappa light chain expression. i, j A representative diffuse infiltrative pattern of a lymph node biopsy in a patient with EMWM, MYD88 mutation positive, ×40 and × 80 magnification. k CD20 stain on abnormal small lymphoid cells, ×80 magnification. l CD138 stain on few admixed plasmacytoid and plasma cells, ×80 magnification. m, o Immunophenotypic profiling of CD19 and CD20 positive small B-cells with kappa light chain restriction and were negative for CD5 and CD10. p Identical monotypic kappa light chain expression in the lymphoid cells was also seen in the plasmacytoid and plasma cells

Mentions: A total of 106 patients were confirmed as having EMWM at time of diagnosis, with a median follow-up time of 63 months; 67 patients (63.4 %) were male while 39 patients were female (36.6 %) (Fig. 1a). Seventy (66 %) patients were less than 65 years old (Fig. 1b), and lymph nodes in the abdomen were the most common extramedullary site (n = 71). Other extramedullary sites included axillary or mediastinal lymph nodes (n = 34), head/neck lymph nodes (n = 24), spleen (n = 23), pleura (n = 13), abdominal mass (n = 8), kidney (n = 5), liver (n = 2), central nervous system (n = 2), muscle (n = 2), orbital soft tissue (n = 1), maxillary sinus (n = 1), and adipose tissue (n = 1). Bone marrow involvement of these patients was interstitial in most cases (56 %) (Fig. 1c). The tissue or bone marrow involvement pattern and immunophenotypic profiling of representative EMWM and BMWM patients are shown in Fig. 2. Regardless of BMWM and EMWM, the neoplastic cells commonly exhibit a diffuse infiltrative pattern and are mainly composed of abnormal small lymphoid cells admixed with variable plasmacytoid cells and plasma cells (Fig. 2a–c, i–j). They are negative for CD5, CD10, and CD23 but with strong monotypic immunoglobulin light chain expression (Fig. 2o).Fig. 1


Waldenström macroglobulinemia with extramedullary involvement at initial diagnosis portends a poorer prognosis.

Cao X, Ye Q, Orlowski RZ, Wang X, Loghavi S, Tu M, Thomas SK, Shan J, Li S, Qazilbash M, Yin CC, Weber D, Miranda RN, Xu-Monette ZY, Medeiros LJ, Young KH - J Hematol Oncol (2015)

The tissue or bone marrow involvement pattern and immunophenotypic profiling of the EMWM and BMWM patients. a, b A representative diffuse interstitial pattern of bone marrow biopsy in a patient with BMWM, ×40 and × 80 magnification. c Bone marrow aspirate smear showed many abnormal small lymphoid cells admixed with variable plasmacytoid cells and plasma cells, ×80 magnification. d CD20 stain on the abnormal small lymphoid cells, ×80 magnification. e CD138 stain on the plasmacytoid and plasma cells, ×80 magnification. f, g Immunophenotypic profiling of CD38 and CD138 positive plasmacytoid and plasma cells with strong monotypic cytoplasmic kappa light chain expression. h The abnormal small lymphoid cells were CD20 positive and showed monotypic kappa light chain expression. i, j A representative diffuse infiltrative pattern of a lymph node biopsy in a patient with EMWM, MYD88 mutation positive, ×40 and × 80 magnification. k CD20 stain on abnormal small lymphoid cells, ×80 magnification. l CD138 stain on few admixed plasmacytoid and plasma cells, ×80 magnification. m, o Immunophenotypic profiling of CD19 and CD20 positive small B-cells with kappa light chain restriction and were negative for CD5 and CD10. p Identical monotypic kappa light chain expression in the lymphoid cells was also seen in the plasmacytoid and plasma cells
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4487966&req=5

Fig2: The tissue or bone marrow involvement pattern and immunophenotypic profiling of the EMWM and BMWM patients. a, b A representative diffuse interstitial pattern of bone marrow biopsy in a patient with BMWM, ×40 and × 80 magnification. c Bone marrow aspirate smear showed many abnormal small lymphoid cells admixed with variable plasmacytoid cells and plasma cells, ×80 magnification. d CD20 stain on the abnormal small lymphoid cells, ×80 magnification. e CD138 stain on the plasmacytoid and plasma cells, ×80 magnification. f, g Immunophenotypic profiling of CD38 and CD138 positive plasmacytoid and plasma cells with strong monotypic cytoplasmic kappa light chain expression. h The abnormal small lymphoid cells were CD20 positive and showed monotypic kappa light chain expression. i, j A representative diffuse infiltrative pattern of a lymph node biopsy in a patient with EMWM, MYD88 mutation positive, ×40 and × 80 magnification. k CD20 stain on abnormal small lymphoid cells, ×80 magnification. l CD138 stain on few admixed plasmacytoid and plasma cells, ×80 magnification. m, o Immunophenotypic profiling of CD19 and CD20 positive small B-cells with kappa light chain restriction and were negative for CD5 and CD10. p Identical monotypic kappa light chain expression in the lymphoid cells was also seen in the plasmacytoid and plasma cells
Mentions: A total of 106 patients were confirmed as having EMWM at time of diagnosis, with a median follow-up time of 63 months; 67 patients (63.4 %) were male while 39 patients were female (36.6 %) (Fig. 1a). Seventy (66 %) patients were less than 65 years old (Fig. 1b), and lymph nodes in the abdomen were the most common extramedullary site (n = 71). Other extramedullary sites included axillary or mediastinal lymph nodes (n = 34), head/neck lymph nodes (n = 24), spleen (n = 23), pleura (n = 13), abdominal mass (n = 8), kidney (n = 5), liver (n = 2), central nervous system (n = 2), muscle (n = 2), orbital soft tissue (n = 1), maxillary sinus (n = 1), and adipose tissue (n = 1). Bone marrow involvement of these patients was interstitial in most cases (56 %) (Fig. 1c). The tissue or bone marrow involvement pattern and immunophenotypic profiling of representative EMWM and BMWM patients are shown in Fig. 2. Regardless of BMWM and EMWM, the neoplastic cells commonly exhibit a diffuse infiltrative pattern and are mainly composed of abnormal small lymphoid cells admixed with variable plasmacytoid cells and plasma cells (Fig. 2a–c, i–j). They are negative for CD5, CD10, and CD23 but with strong monotypic immunoglobulin light chain expression (Fig. 2o).Fig. 1

Bottom Line: Kaplan-Meier survival analysis results showed that EMWM patients had a significantly shorter median overall survival (P < 0.001) and progression-free survival (PFS) (P < 0.001) than did BMWM patients.Additionally, initial treatment with rituximab significantly improved the PFS of BMWM patients (P = 0.012) but had no effect on EMWM patients.However, EMWM patients treated with nucleoside analogs attained a better PFS than those who did not (P = 0.021).

View Article: PubMed Central - PubMed

Affiliation: Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX, 77030, USA. cathyjiangsu@163.com.

ABSTRACT

Background: The prognostic importance of extramedullary involvement in patients with Waldenström macroglobulinemia (WM) at diagnosis and treatment options for these patients has not been well evaluated. In this study, we investigated the clinical manifestations, biological features, and effect of first-line therapy on the outcome of WM patients diagnosed with extramedullary involvement (EMWM) vs those with only bone marrow involvement (BMWM).

Methods: We analyzed the clinical data of 312 WM patients diagnosed with EMWM (n = 106) and BMWM (n = 206) at The University of Texas MD Anderson Cancer Center from 1994 to 2014. EMWM was confirmed by biopsy, positron emission tomography-computed tomography, or magnetic resonance imaging, and clinical laboratory analyses.

Results: Characteristics associated with EMWM were male sex (P = 0.027), age younger than 65 years (P = 0.048), presence of B symptoms (P < 0.001), high serum beta-2 macroglobulin (P < 0.001) level, low serum albumin level (P = 0.036), and cytogenetic abnormalities (P = 0.010). Kaplan-Meier survival analysis results showed that EMWM patients had a significantly shorter median overall survival (P < 0.001) and progression-free survival (PFS) (P < 0.001) than did BMWM patients. Chemotherapy combined with targeted therapy improved PFS for BMWM patients (P = 0.004) but not for EMWM patients. Additionally, initial treatment with rituximab significantly improved the PFS of BMWM patients (P = 0.012) but had no effect on EMWM patients. However, EMWM patients treated with nucleoside analogs attained a better PFS than those who did not (P = 0.021).

Conclusions: We show that extramedullary involvement at diagnosis is an adverse prognostic factor in WM patients and that first-line therapy with nucleoside analogs improved PFS for patients with EMWM. The study provides unique clinical and treatment observations in subtypes of WM patients.

No MeSH data available.


Related in: MedlinePlus