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Risk factors for hypogammaglobulinemia after allo-SCT

Bone Marrow Transplantation volume 49, pages 859–861 (2014)Cite this article

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Allo-SCT is an established therapy primarily used to eradicate various types of hematological malignancy. However, defects in cellular and humoral immunity persist for months (even years) after allo-SCT. Successful reconstitution of the immune system is important for decreasing the complications of allo-SCT, such as infections and GVHD. Thus, identification of the risk factors for hypogammaglobulinemia will help in improving the outcomes of patients undergoing allo-SCT. However, to the best of our knowledge, only one large-scale study has explored the risk factors for hypogammaglobulinemia in adults.1 The authors of that study found that acute GVHD (aGVHD), younger patients, lack of treatment with anti-thymocyte globulin (ATG), female donor to male recipient and treatment with CsA and MTX as prophylaxis against aGVHD were associated significantly with an increased risk for hypogammaglobulinemia after allo-SCT. However, that study did not involve newly developed procedures such as cord blood transplantation (CBT) or analyses of mycophenolate mofetil (MMF) usage as prophylaxis for GVHD. In a recent study of 185 pediatric patients undergoing allo-SCT, the risk factors identified for hypogammaglobulinemia were younger age, lower pretransplant IgG level, malignant disease, use of unrelated donor stem cell source and development of aGVHD.2

We retrospectively investigated the risk factors for hypogammaglobulinemia in adult patients who underwent allo-SCT within our department between January 2001 and June 2012. This study was approved by the ethics committee of Kyoto University (E1714). These subjects survived ⩾28 days, and their Ig levels were measured before conditioning regimens and at least twice after allo-SCT. We assessed 299 cases of allo-SCT in 278 patients. Patient characteristics and allo-SCT procedures are summarized in Table 1. Patients with multiple myeloma were excluded. Patients were divided into ‘high-risk’ and ‘standard-risk’ groups according to transplantation risk.3 Disease status at allo-SCT was divided into ‘controlled’ and ‘progressive’ disease.4 With respect to conditioning regimens, the definitions of myeloablative conditioning and reduced-intensity conditioning (RIC) were consistent with those of the RIC regimen workshop.5 The prophylaxis of aGVHD comprised a calcineurin inhibitor (CsA or FK506) plus short-term MTX,6 MMF (30 mg/kg/day, orally from day 0 until day 30), or both. ATG was not used in any case. Grade 2–4 aGVHD and extensive chronic GVHD (cGVHD) were treated with corticosteroids. Serum IgG levels were measured before conditioning regimens, at 2 weeks, 1, 3, 6 and 9 months and 1 and 3 years after allo-SCT. Once relapse was diagnosed, subsequent data on IgG levels were excluded from the study. IgG levels were additionally measured as clinically indicated. Hypogammaglobulinemia was defined as serum IgG level <400 mg/dL, and patients whose IgG level was <400 mg/dL at least once were included in the hypogammaglobulinemia group. Patients with hypogammaglobulinemia or other conditions (for example, severe infection) received i.v. Ig replacement therapy according to the decision of the attending physician. Serum IgG levels after allo-SCT were compared with those before conditioning regimens using unpaired t tests. Univariate analyses of the cumulative incidence of hypogammaglobulinemia were undertaken using Kaplan–Meier methods considering relapse and TRM as a censor. Patients with GVHD only after the diagnosis of hypogammaglobulinemia were included in the non-GVHD group in this analysis. Factors with P<0.1 and occurrence of GVHD were subjected to multivariate analyses using Cox proportional hazard models. Statistical analyses were performed using R ver 2.13.0 (R Foundation for Statistical Computing, Vienna, Austria). The alpha level of all tests or the P-value was set at 0.05.

Table 1 Patient characteristics
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Acknowledgements

This research was supported by grants-in-aid for scientific research from the Japan Society for the Promotion of Science (23591474) to KY

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  1. Department of Hematology and Oncology, Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Y Arai, K Yamashita, K Mizugishi, T Kondo, T Kitano, M Hishizawa, N Kadowaki & A Takaori-Kondo

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  1. Y Arai
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Correspondence to K Yamashita.

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Arai, Y., Yamashita, K., Mizugishi, K. et al. Risk factors for hypogammaglobulinemia after allo-SCT. Bone Marrow Transplant 49, 859–861 (2014). https://doi.org/10.1038/bmt.2014.28

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