Objective: To investigate the efficacy and safety of Bruton tyrosine kinase inhibitors (BTKi) ibrutinib or zanubrutinib monotherapy in newly diagnosed patients with Waldenström macroglobulinemia (WM) . Methods: The efficacy and adverse effects of 58 patients with newly diagnosed WM receiving BTKi monotherapy in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were analyzed retrospectively from January 2018 to August 2022. Results: The response of 55 patients may be examined. Forty patients received ibrutinib monotherapy for a median of 15 months, with an overall response rate (ORR) of 85%, a main remission rate (MRR) of 70%, and a very good partial remission (VGPR) rate of 10%. Fifteen patients received zanubrutinib monotherapy for a median of 13 months, with an ORR of 93%, an MRR of 73%, and a VGPR rate of 0%. For various reasons, 10 patients were converted from ibrutinib to zanubrutinib. Ibrutinib treatment lasted an average of 7.5 months before conversion. The median duration of zanubrutinib therapy after conversion was 3.5 months. The ORRs before and after conversion were 90% and 100%, MRRs were 80% and 80%, and VGPR rates were 10% and 50%, respectively. After a median of 16 months, the 24-month progression-free survival (PFS) rate of patients who received both BTKi was 86%. PFS did not differ statistically across individuals with low, medium, and high-risk ISS scores (P=0.998). All of the patients survived. The most common side effects of BTKi were neutropenia and thrombocytopenia, which occurred in 12% and 10% of all patients, respectively. Ibrutinib accounts for 5% of atrial fibrillation, and zanubrutinib has a 7% risk of bleeding. Conclusions: In treating WM, ibrutinib or zanubrutinib provides good efficacy and tolerable adverse effects.
Humans ; China ; Retrospective Studies ; Treatment Outcome ; Tyrosine Protein Kinase Inhibitors/therapeutic use* ; Waldenstrom Macroglobulinemia/drug therapy*

No abstract available.
Drug Therapy* ; Waldenstrom Macroglobulinemia*

PURPOSE: The authors report a case of bilateral simultaneous central retinal vein occlusion caused by Waldenstrom's macroglobulinemia. CASE SUMMARY: A 65-year-old man presented to our department complaining of decreased visual acuity for the duration of about 6 months. On his initial visit, best-corrected visual acuity was 0.02 in the right eye and 0.06 in the left eye. Based on the findings of a funduscopic examination, the patient had bilateral diffuse retinal hemorrhages, dilated tortuous veins, and macular edema. He had experienced recurrent spontaneous epistaxis 6 months previously and had undergone treatments such as intravitreal bevacizumab injection and intravitreal dexamethasone implantation at another hospital. Laboratory tests at that hospital showed anemia and hyperproteinemia, for which he was referred to our hemato-oncology department. Bone marrow biopsy was consistent with Waldenstrom's macroglobulinemia/lymphoplasmacytoid lymphoma, and he was treated with systemic chemotherapy. One year after the systemic chemotherapy, his best-corrected visual acuity was 0.15 in the right eye and 0.6 in the left eye. Funduscopy showed decreased bilateral retinal hemorrhages and macular edema. CONCLUSIONS: When simultaneous bilateral central retinal vein occlusion occurs in a patient with no other underlying disease such as hypertension or diabetes, it might be a sign of serum hyperviscosity, and there should be a very high level of suspicion for presence or progression of systemic disease. If such a disease is properly and timely diagnosed, effective early systemic evaluation and therapy can be administered, and it is important to have initial general treatment as well as ophthalmic treatment.
Aged ; Anemia ; Bevacizumab ; Biopsy ; Bone Marrow ; Dexamethasone ; Drug Therapy ; Epistaxis ; Humans ; Hypertension ; Lymphoma ; Macular Edema ; Retinal Hemorrhage ; Retinal Vein* ; Veins ; Visual Acuity ; Waldenstrom Macroglobulinemia*

OBJECTIVE To study the morphology, immunology, cyto- and molecular genetics of a patient with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia (LPL/WM), deletion of P53 gene and rearrangement of clonal T cell receptors-delta (TCR-delta) gene. METHODS The cell morphology and immunocytochemistry were analyzed by bone marrow testing and biopsy. Cellular immunology was analyzed by flow cytometry. Genetic analysis was carried out by chromosome karyotyping, fluorescent in situ hybridization (FISH) and polymerase chain reaction (PCR). Immunoglobulin M (IgM) in serum and urine was assayed by immunofixation electrophoresis. And the effect of chlorambucil therapy was evaluated. RESULTS Bone marrow biopsy suggested that the patient was of B lymphocyte type and had abnormal increase of lymphocytoid plasma cells, which were CD38 and CD138 positive. The patient had a normal male karyotype. FISH and PCR analysis of peripheral blood samples suggested deletion of P53 gene and rearrangement of TCR-delta gene. Immunofixation electrophoresis has detected IgM-kappa in both serum and urine. The patient showed partial response to chlorambucil. CONCLUSION In addition to typical clinical features, bone marrow examination, flow cytometry, histochemistry and immunophenotyping, testing for P53 gene deletion and lymphocyte gene rearrangement can facilitate the diagnosis and treatment of LPL/WM.
Aged ; Gene Rearrangement, delta-Chain T-Cell Antigen Receptor ; Genes, p53 ; Humans ; In Situ Hybridization, Fluorescence ; Male ; Polymerase Chain Reaction ; Waldenstrom Macroglobulinemia ; drug therapy ; genetics

Antibodies, Monoclonal, Murine-Derived ; adverse effects ; Antineoplastic Agents ; adverse effects ; Humans ; Lung Diseases, Interstitial ; chemically induced ; Rituximab ; Waldenstrom Macroglobulinemia ; drug therapy

Aged ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Retinal Detachment ; complications ; drug therapy ; Waldenstrom Macroglobulinemia ; complications ; drug therapy

Waldenstrom macroglobulinemia (WM) is a B-cell lymphoproliferative disorder associated with bone marrow involvement of lymphoplasmacytic lymphoma (LPL) and an IgM monoclonal gammopathy. Generally B-lymphocytes in LPL do not express CD5 that is important for differential diagnosis of B-cell lymphoproliferative disorders. In WM, various renal diseases and type I cryoglobulinemia are well described separately, but cryoglobulinemic glomerulonephropathy is very rarely reported. A 61-yr-old woman complained of generalized edema, cyanosis of the extremities in cold weather, visual disturbance, and pancytopenia. Bone marrow and renal biopsy showed CD5+ expressing B-cells and cryoglobulinemic glomerulonephropathy. With the diagnosis of WM, she received cyclophosphamide, doxorubicin, vincristine and prednisolone chemotherapy and got complete remission. Here, we report a rare case of WM associated with unusual expression of CD5+ B-lymphocytes and cryoglobulinemic glomerulonephropathy, and emphasize the importance of the clinical features in differentiating CD5+ B-cell lymphoproliferative disorders.
Antigens, CD5/*metabolism ; Antineoplastic Agents/therapeutic use ; B-Lymphocytes/immunology/metabolism ; Bone Marrow/pathology ; Cryoglobulinemia/diagnosis ; Cyclophosphamide/therapeutic use ; Diagnosis, Differential ; Doxorubicin/therapeutic use ; Drug Therapy, Combination ; Female ; Glomerulonephritis/*diagnosis/pathology ; Humans ; Kidney/pathology ; Middle Aged ; Paraproteinemias/diagnosis ; Prednisolone/therapeutic use ; Vincristine/therapeutic use ; Waldenstrom Macroglobulinemia/*diagnosis/drug therapy/pathology

OBJECTIVETo explore the clinicopathologic features of lymphoplasmacytic lymphomas (LPL).

METHODSRoutine histological examination was performed on hematoxylin-eosin stained sections of 24 bone marrow biopsies and available 6 concurrent lymph node specimens. Immunohistochemistry study was performed using EliVision methods.

RESULTSAmong 24 cases, the male-to-female ratio was 2.4:1 and the median age was 59.5 years (42 - 75). The most common symptom was weakness (83.3%, 20/24). Hyperviscosity and "B" symptoms occurred in 20.8% (5/24) and 8.3% (2/24) respectively. 41.7% (10/24) patients presented with lymphadenopathy. Anemia, leukocytosis and thrombocytopenia were seen in 79.2% (19/24), 8.3% (2/24) and 37.5% (9/24) respectively. Monoclonal Ig light chain expression was detected by serum immunofixation electrophoresis in 23 cases (95.8%), including IgM (20 cases), IgG (2 cases) and IgA (1 case). Basing on the histology and immunohistochemistry findings, the diagnosis was made in 22 bone marrow and 2 lymph node biopsies, respectively. Histologically, the bone marrow and lymph node specimens composed of small lymphocytes, plasmacytoid lymphocytes and plasma cells. The most frequent pattern of bone marrow involvement was diffuse in appearance (63.6%, 14/22), while nodular and interstitial patterns were less common (22.7%, 5/22 and 13.6%, 3/22, respectively). Lymph node involvement was also to be diffuse in pattern. The proliferative cells expressed Pax5, CD20, CD38 and CD138, but were negative for CD5, CD10, CD23, CyclinD1, CD3, CD7 and MPO.

CONCLUSIONSLPL has distinct clinicopathological features. Histological and immunohistochemistry findings are important for its differential diagnosis with chronic lymphocytic leukemia/small lymphocytic lymphoma, splenic marginal zone lymphoma and follicular lymphoma. Waldenström macroglobulinemia is LPL.

ADP-ribosyl Cyclase 1 ; metabolism ; Adult ; Aged ; Antigens, CD20 ; metabolism ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bone Marrow ; pathology ; Cyclophosphamide ; therapeutic use ; Diagnosis, Differential ; Doxorubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Immunoglobulin Light Chains ; metabolism ; Immunophenotyping ; Leukemia, Lymphocytic, Chronic, B-Cell ; metabolism ; pathology ; Lymph Nodes ; pathology ; Lymphoma, B-Cell, Marginal Zone ; metabolism ; pathology ; Lymphoma, Follicular ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Invasiveness ; PAX5 Transcription Factor ; metabolism ; Prednisone ; therapeutic use ; Splenic Neoplasms ; metabolism ; pathology ; Survival Rate ; Syndecan-1 ; metabolism ; Vincristine ; therapeutic use ; Waldenstrom Macroglobulinemia ; drug therapy ; metabolism ; pathology

OBJECTIVETo study the morphologic features, immunophenotype, differential diagnosis and prognosis of nodal marginal zone B-cell lymphoma (NMZL).

METHODSLight microscopic examination and immunohistochemical study were carried out in 10 cases of NMZL. Seven of which had follow-up information available.

RESULTSAll cases presented with good performance status at the time of diagnosis. Amongst the 7 cases with follow-up information available, most (6/7) were in advanced clinical stage (stage II to III). The one-year survival rate was 67%. A vaguely nodular growth pattern was observed in most cases of NMZL (5/10). The lymphoma was composed predominantly of atypical lymphoid cells resembling centrocytes (7/10). A predominance of monocytoid B-cell (2/10) or small lymphocytic (1/10) morphology was rare. Instead, the presence of a minor component of monocytoid B cells was not uncommon (5/10). Plasmacytoid or plasmacytic cells were also frequently found (8/10). The proliferation index ranged from 5% to 50%. Follicular dendritic cells appeared atrophic in 7 cases and variably hyperplasic in 3 cases.

CONCLUSIONSPrimary NMZL is rare. It has a unique growth pattern and most cases are composed predominantly of cells resembling centrocytes. Differential diagnosis includes lymphoplasmacytic lymphoma, lymph node involvement by extranodal marginal zone B-cell lymphoma and T-zone hyperplasia. The clinical stage is often high at presentation, with systemic dissemination. The prognosis of NMZL is thus relatively poor.

Adult ; Aged ; Diagnosis, Differential ; Female ; Follow-Up Studies ; Humans ; Lymph Nodes ; pathology ; Lymphoma, B-Cell, Marginal Zone ; drug therapy ; metabolism ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Remission Induction ; Survival Rate ; Waldenstrom Macroglobulinemia ; pathology

The treatment outcomes with conventional second-line chemotherapy or radiotherapy aregenerally very poor for patients with relapsed primary CNS lymphoma (PCNSL). We treated three relapsed PCNSL patients with high-dose cytarabine plus etoposide (CYVE) chemotherapy, and this was followed by autologous stem cell transplantation (ASCT). The salvage CYVE chemotherapy consisted of cytarabine 2g/m2/d on days 2 to 5 in a 3-hour infusion and 50mg/m2/d on days 1 to 5 in a 12-hourinfusion, and etoposide 200mg/m2/d on days 2 to 5 in a 2-hour infusion. After two cycles of CYVE chemotherapy, two patients achieved a complete response (CR), and one patient achieved a partial response (PR). All three patients experienced febrile neutropenia and grade 4 thrombocytopenia with the CYVE chemotherapy. However, the hematologic toxicities were well managed without any complications. The conditioning regimen for ASCT consisted of BCNU 300mg/m2 on day -7, etoposide 100mg/m2 on days -6 to -3, cytarabine 100mg/m2 on days -6 to -3, and cyclophosphamide 35mg/kg on days -6 to -3 (BEAC). After ASCT, the patient who initially showed a PR with CYVE chemotherapy then achieved a CR. At the time of this report, one patient remained alive in CR for 41 months after CYVE chemotherapy. The remaining two patients experienced relapse 5 months and 4 months after ASCT, respectively, and they ultimately died of disease progression 18 months and 8 months after ASCT, respectively. In our cases, the CYVE chemotherapy+ASCT was well tolerated, and this induced the complete disappearance of the tumor, and one patient showed prolonged disease-free survival. CYVE chemotherapy+ASCT could be a treatment option for relapsed PCNSL.
Anemia, Hemolytic, Autoimmune ; Carmustine ; Cyclophosphamide ; Cytarabine* ; Disease Progression ; Disease-Free Survival ; Drug Therapy ; Etoposide* ; Febrile Neutropenia ; Humans ; Lymphoma* ; Radiotherapy ; Recurrence ; Stem Cell Transplantation* ; Stem Cells* ; Thrombocytopenia ; Waldenstrom Macroglobulinemia