IgA and IgG hypogammaglobulinemia in Waldenstr?m’s macroglobulinemia

Background

Hypogammaglobulinemia is common in Waldenström’s macroglobulinemia. The etiology of this finding remains unclear, but it has been speculated to be based on tumor-induced suppression of the ‘uninvolved’ immunoglobulin production

Design and Methods

We evaluated the incidence of IgA and IgG hypogammaglobulinemia in 207 untreated patients with Waldenström’s macroglobulinemia and investigated the associated clinicopathological findings and impact of therapy. We also sequenced eight genes (AICDA, BTK, CD40, CD154, NEMO, TACI, SH2D1A, UNG) implicated in immunoglobulin deficiency in 19 Waldenström’s macroglobulinemia patients with IgA and/or IgG hypogammaglobulinemia.

Results

At baseline 63.3%, 58.0% and 49.3% of the 207 patients had abnormally low serum levels of IgA, IgG, or both. No association between IgA and IgG hypogammaglobulinemia and disease burden, serum IgM levels, β₂-microglobulin, International Prognostic Scoring System score, or incidence of recurrent infections was observed, although the presence of adenopathy and/or splenomegaly was associated with a lower incidence of hypogammaglobulinemia. Lower IgA and IgG levels were associated with disease progression in patients managed with a ‘watch and wait’ strategy. IgA and/or IgG levels remained abnormally low despite response to treatment, including complete remissions. A missense mutation in the highly conserved catalytic site of UNG was observed in a patient with hypogammaglobulinemia, warranting further study of this pathway in Waldenström’s macroglobulinemia.

Conclusions

IgA and IgG hypogammaglobulinemia is common in Waldenström’s macroglobulinemia and persists despite therapeutic intervention and response. IgA and IgG hypogammaglobulinemia does not predict the risk of recurrent infections in patients with Waldenström’s macroglobulinemia, although lower levels of serum IgA and IgG are associated with disease progression in Waldenström’s macroglobulinemia patients being managed with a ‘watch and wait’ strategy.     

Detection of MYD88 L265P mutations in formalin-fixed and decalcified BM biopsies from patients with lymphoplasmacytic lymphoma

The diagnosis of bone marrow (BM) infiltration by Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) poses a diagnostic challenge in hematopathology. No definitive morphology or immunophenotype is able to distinguish between infiltration of paraffin-embedded BM sections by WM/LPL and other indolent lymphomas, in particular those of the splenic marginal zone (SMZL) which may also show plasmacytic maturation. An oncogenic gain-of-function mutation (L265P) in the human MYD88 gene has been found to be present in most cases of WM/LPL, yet is absent in most other cases of B-cell chronic lymphoproliferative disorders (LPD), including SMZL. Here, we compare two newly developed diagnostic protocols for detection of this mutation in paraffin-embedded archival tissues which are particularly applicable to decalcified BM biopsies. Sanger sequencing can easily detect levels of BM infiltration above 15% by WM lymphoplasmacytic cells, while the allele-specific PCR can detect the L265P mutation in BM infiltrations below 1% of lymphoma cells. We show that these methods are easily applicable to archival BM specimens and markedly improve diagnostic accuracy of BM infiltrations by indolent B-cell lymphomas.     

16例淋巴浆细胞淋巴瘤/华氏巨球蛋白血症临床特点

本研究旨在探讨淋巴浆细胞淋巴瘤/华氏巨球蛋白血症（lymphoplasmacytic lymphoma,LPL/Waldenstrm macroglobulinemia,WM）的临床特点、诊断及治疗方法。回顾性分析16例淋巴浆细胞淋巴瘤/华氏巨球蛋白血症患者的临床特点、骨髓细胞形态学及病理检查特点、治疗方法。结果表明：16例淋巴浆细胞淋巴瘤/华氏巨球蛋白血症患者的平均发病年龄为65.1岁,贫血和高粘综合征是最常见的表现;骨髓检查可见淋巴细胞、淋巴浆细胞或浆细胞增多;淋巴结活检可见瘤细胞弥漫分布,免疫组织化学检测显示表达B细胞相关抗原;经治疗后总反应率（overall response rate,ORR）81.3%,完全缓解25%,生存时间6-108月,其中3例死亡,生存率为81.3%。结论：淋巴浆细胞淋巴瘤/华氏巨球蛋白血症患者的疾病过程具有低度恶性B细胞淋巴瘤的特点,病程较长,经治疗可获缓解,但不易治愈,部分患者可转化为中高度恶性淋巴瘤。     

Waldenstrom巨球蛋白血症26例临床特征与治疗分析

【目的】加深对Waldenstrom巨球蛋白血症（WM）的临床特征及治疗的认识。【方法】回顾性分析26例WM患者的临床资料。【结果】主要临床特征：乏力,头晕、头痛、嗜睡、意识障碍等血液粘滞综合征表现,出血,体重下降等症状较常见;贫血貌、肝脾肿大、淋巴结肿大等体征常见;辅助检查：血清单克隆IgM≥10g／L,骨髓浆细胞样淋巴细胞浸润等。【结论]WM首发症状多种多样,早期容易误诊。对于出现高粘滞综合征表现,颅脑CT或MRI检查未见明显异常的老年男性患者,应想到WM的可能性,并及早进行血清蛋白电泳、免疫球蛋白、免疫固定电泳、骨髓穿刺或骨髓活检等检查,以减少漏诊、误诊。WM目前尚无特效的治疗方法,血浆置换联合化疗可以迅速缓解巨球蛋白血症患者的高粘滞综合征的症状,取得较好的效果。