Chapter 106. Plasma Cell Disorders (Part 10)

Chia sẻ: Thuoc Thuoc | Ngày: | Loại File: PDF | Số trang:9

Thêm vào BST

Báo xấu

77
lượt xem 7
download

Download Vui lòng tải xuống để xem tài liệu đầy đủ

Heavy Chain Diseases The heavy chain diseases are rare lymphoplasmacytic malignancies. Their clinical manifestations vary with the heavy chain isotype. Patients secrete a defective heavy chain that usually has an intact Fc fragment and a deletion in the Fd region. Gamma, alpha, and mu heavy chain diseases have been described, but no reports of delta or epsilon heavy chain diseases have appeared. Molecular biologic analysis of these tumors has revealed structural genetic defects that may account for the aberrant chain secreted. Gamma Heavy Chain Disease (Franklin's Disease) This disease affects individuals of widely different age groups and countries of origin. It...

Chủ đề:

Bình luận(0) Đăng nhập để gửi bình luận!

Lưu

Nội dung Text: Chapter 106. Plasma Cell Disorders (Part 10)

Chapter 106. Plasma Cell Disorders (Part 10) Heavy Chain Diseases The heavy chain diseases are rare lymphoplasmacytic malignancies. Their clinical manifestations vary with the heavy chain isotype. Patients secrete a defective heavy chain that usually has an intact Fc fragment and a deletion in the Fd region. Gamma, alpha, and mu heavy chain diseases have been described, but no reports of delta or epsilon heavy chain diseases have appeared. Molecular biologic analysis of these tumors has revealed structural genetic defects that may account for the aberrant chain secreted. Gamma Heavy Chain Disease (Franklin's Disease) This disease affects individuals of widely different age groups and countries of origin. It is characterized by lymphadenopathy, fever, anemia, malaise, hepatosplenomegaly, and weakness. Its most distinctive symptom is palatal edema, resulting from involvement of nodes in Waldeyer's ring, and this
may progress to produce respiratory compromise. The diagnosis depends on the demonstration of an anomalous serum M component [often
paraaortic adenopathy. Respiratory tract involvement occurs rarely. Patients may vary widely in their clinical course. Some may develop diffuse aggressive histologies of malignant lymphoma. Chemotherapy may produce long-term remissions. Rare patients appear to have responded to antibiotic therapy, raising the question of the etiologic role of antigenic stimulation, perhaps by some chronic intestinal infection. Chemotherapy plus antibiotics may be more effective than chemotherapy alone. Immunoproliferative small intestinal disease (IPSID) is recognized as an infectious pathogen–associated human lymphoma that has association with Campylobacter jejuni. It involves mainly the proximal small intestine resulting in malabsorption, diarrhea, and abdominal pain. IPSID is associated with excessive plasma cell differentiation and produces truncated alpha heavy chain proteins lacking the light chains as well as the first constant domain. Early-stage IPSID responds to antibiotics (30–70% complete remission). Most untreated IPSID patients progress to lymphoplasmacytic and immunoblastic lymphoma. Mu Heavy Chain Disease The secretion of isolated mu heavy chains into the serum appears to occur in a very rare subset of patients with chronic lymphocytic leukemia. The only features that may distinguish patients with mu heavy chain disease are the presence of vacuoles in the malignant lymphocytes and the excretion of kappa light chains in the urine. The diagnosis requires ultracentrifugation or gel filtration
to confirm the nonreactivity of the paraprotein with the light chain reagents, because some intact macroglobulins fail to interact with these serums. The tumor cells seem to have a defect in the assembly of light and heavy chains, because they appear to contain both in their cytoplasm. There is no evidence that such patients should be treated differently from other patients with chronic lymphocytic leukemia (Chap. 105). Further Readings Ghobrial IM et al: Waldenström macroglobulinaemia. Lancet Oncol 4:679, 2003 [PMID: 14602248] Harousseau JL, Moreau P: Evolving role of stem cell transplantation in multiple myeloma. Clin Lymphoma Myeloma 6:89, 2005 [PMID: 16231846] Hideshima T et al: Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nature Rev Cancer 7:585, 2007 [PMID: 17646864] The International Myeloma Working Group: Criteria for the classification of monoclonal gammopathies, multiple myeloma and related disorders: A report
of the International Myeloma Working Group. Br J Haematol 121:749, 2003 Kuehl WM, Bergsagel PL: Multiple myeloma: Evolving genetic events and host interactions. Nature Rev Cancer 2:175, 2002 [PMID: 11990854] Kyle RA, Rajkumar SV: Multiple myeloma. N Engl J Med 351:1860, 2004 [PMID: 15509819] ——— et al: Prevalence of monoclonal gammopathy of undetermined significance. N Engl J Med 354:1362, 2006 ——— et al: American Society of Clinical Oncology 2007 clinical practice guideline update on the role of bisphosphonates in multiple myeloma. J Clin Oncol 25:2464, 2007 Mitsiades CS et al: Focus on multiple myeloma. Cancer Cell 6:439, 2005 Munshi NC, Anderson KC: Plasma cell neoplasm, in Principles and Practice of Oncology, 7th ed, V DeVita, S Rosenberg, S Hellman (eds). Philadelphia, Lippincott–Raven Publishers, 2005
Treon SP et al: Update on treatment recommendations from the Third International Workshop on Waldenström's macroglobulinemia. Blood 107:3442, 2006 [PMID: 16410453] Wahner-Roedler DL et al: Gamma-heavy chain disease: Review of 23 cases. Medicine 82:236, 2003 [PMID: 12861101] Bibliography Attal M et al: A prospective, randomized trial of autologous bone marrow transplantation and chemotherapy in multiple myeloma. N Engl J Med 335:91, 1996 [PMID: 8649495] Attal M et al: InterGroupe Francophone du Myelome. Single versus double autologous stem-cell transplantation for multiple myeloma. N Engl J Med 349:2495, 2003 [PMID: 14695409] Attal M et al: Maintenance therapy with thalidomide improves survival in multiple myeloma patients. Blood 2006 Jul 27; [Epub ahead of print] Berenson JR et al: Efficacy of pamidronate in reducing skeletal events in
patients with advanced multiple myeloma. N Engl J Med 334:488, 1996 [PMID: 8559201] Berenson JR et al: American Society of Clinical Oncology clinical practice guidelines: The role of bisphosphonates in multiple myeloma. J Clin Oncol 20:3719, 2002 [PMID: 12202673] Berenson JR et al: Maintenance therapy with alternate-day prednisone improves survival in multiple myeloma patients. Blood 99:3163, 2002 [PMID: 11964279] Dispenzieri A et al: POEMS syndrome: Definitions and long-term outcome. Blood 101:2496, 2003 [PMID: 12456500] Gahrton G et al: Progress in allogeneic bone marrow and peripheral blood stem cell transplantation for multiple myeloma: A comparison between transplants performed 1983–93 and 1994–8 at European Group for Blood and Marrow Transplantation centers. Br J Haematol 113:209, 2001 [PMID: 11360893] Greipp PR et al: International staging system for multiple myeloma. J Clin Oncol 23:3412, 2005 [PMID: 15809451]
Hideshima T, Anderson KC: Novel therapeutic approaches for multiple myeloma. Nature Rev Cancer 2:927, 2002 [PMID: 12459731] Holland J et al: Plasmacytoma. Treatment results and conversion to myeloma. Cancer 69:1513, 1992 [PMID: 1540888] Rajkumar SV et al: Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood 106:812, 2005 [PMID: 15855274] Rajkumar SV et al: Phase III clinical trail thalidomide plus dexamethasone compared with dexamethasone alone in newly diagnosed multiple myeloma: A clinical trial coordinated by the Eastern Cooperative Oncology Group. J Clin Oncol 24:431, 2006 [PMID: 16365178] Richardson PG et al: Bortezomib or high-dose dexamethasone for relapsed multiple myeloma. N Engl J Med 352:2487, 2005 [PMID: 15958804] Treon SP et al: Report of the Third International Workshop on Waldenström's macroglobulinemia. Clin Lymphoma 5:215, 2005 [PMID:
15794850]