Polyclonal Immunoglobulin Recovery after Autologous Stem Cell Transplantation Is an Independent Prognostic Factor for Survival Outcome in Patients with Multiple Myeloma

We retrospectively analyzed multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT) without maintenance therapy to assess the impact of recovery of normal immunoglobulin (Ig) on clinical outcomes. The recovery of polyclonal Ig was defined as normalization of all values of serum IgG, IgA, and IgM 1 year after ASCT. Among 50 patients, 26 patients showed polyclonal Ig recovery; 14 patients were in ≥complete response (CR) and 12 remained in non-CR after ASCT. The patients with Ig recovery exhibited a significantly better progression-free survival (PFS, median, 46.8 vs. 26.7 months, p = 0.0071) and overall survival (OS, median, not reached vs. 65.3 months, p < 0.00001) compared with those without Ig recovery. The survival benefits of Ig recovery were similarly observed in ≥CR patients (median OS, not reached vs. 80.5 months, p = 0.061) and non-CR patients (median OS, not reached vs. 53.2 months, p = 0.00016). Multivariate analysis revealed that non-CR and not all Ig recovery were independent prognostic factors for PFS (HR, 4.284, 95%CI (1.868–9.826), p = 0.00059; and HR, 2.804, 95%CI (1.334–5.896), p = 0.0065, respectively) and also for OS (HR, 8.245, 95%CI (1.528–44.47), p = 0.014; and HR, 36.55, 95%CI (3.942–338.8), p = 0.0015, respectively). Therefore, in addition to the depth of response, the recovery of polyclonal Ig after ASCT is a useful indicator especially for long-term outcome and might be considered to prevent overtreatment with maintenance therapy in transplanted patients with MM

カンセツ リウマチ ニ タイスル メトトレキセート チリョウチュウ ニ コウド ノ ハンケッキュウ ゲンショウ オ キタシ シボウ シタ 5レイ ノ ケントウ

Background : Methotrexate （MTX） is placed as an anchor drug of treatment for rheumatoid arthritis （RA）. However, many cases suffered from side effects of MTX such as interstitial pneumonia and hematological toxicity. We investigated ５ cases that died of severe pancytopenia under treatment with low-dose MTX for RA. Methods : We reviewed the clinical features of ５ cases that developed severe pancytopenia and were transferred to Tokushima Prefectural Central Hospital under treatment with low-dose MTX for RA from ２０１１-２０１５. Results : All the cases were women, and were under treatment with low-dose MTX. The periods of medication of MTX were not clear. All the cases had renal insufficiency, and had a severe infection induced by pancytopenia and some cases developed disseminated intravascular coagulation （DIC）. At once we started intensive care, but all patients died in a short term. Conclusions : Women, the elderly, and renal insufficiency can be risk factors of severe pancytopenia induced by MTX even if low dosage. We should carefully treat these patients with MTX

DNA Analysis of Antithrombin III (AT III) Gene in Three Japanese Kindreds with Congenital AT III Deficiency

DNA samples from white blood cells of 9 patients and 10 healthy members in 3 Japanese kindreds (Family Mo, Mi and Tu) with congenital antithrombin III (AT III) deficiency, and of 48 normal Japanese individuals were analysed by Southern blotting method using AT III cDNA probe PA62. Restriction fragment length polymorphism (RFLP) by uses of Pst I and PA62 demonstrated + allele in 50%, - allele in 50%, F allele in 59% and S allele in 41% of 96 alleles from 48 normal Japanese individuals, indicating that the frequencies of RFLP in Japanese are almost the same as those in other races reported before. This suggests that DNA analysis on Japanese families with congenital AT III deficiency was possible using RFLP of AT III gene because of high frequencies of RFLP in normal Japanese. All patients in 3 kindreds with congenital AT III deficiency had a -/+ genotype, indicating that complete deletion of one allele of AT III gene can be neglected. No abnormal DNA fragments were observed by Southern blot analysis of genomic DNAs from the patients in the 3 kindreds digested with various restriction enzymes (Bam HI, Eco RI, Hind III, Bgl II, Bcl I, Kpn I, Pvu II, Sac I, Taq I and Xba I). This suggests that AT III deficiency in our 3 kindreds is not caused by major structural alterations such as partial deletion, rearrangement and duplication, small deletion, insertion or limited nucleotide substitution in the AT III gene. In addition, it was suggested by analysis of polymorphism of AT III gene in the members of Family Mo and Mi that abnormal AT III gene existed on -, F allele in these families

Systemic osteosclerosis associated with primary bone marrow B‐cell lymphoma

Abstract Systemic osteosclerosis is a rare complication of hematological malignancies. Primary myelofibrosis and acute megakaryocytic leukemia are known as underlying diseases; however, lymphoid tumors have rarely been reported. Here we describe a case of a 50‐year‐old man with severe systemic osteosclerosis associated with primary bone marrow B‐cell lymphoma. Analysis of bone metabolic markers revealed a high turnover of bone metabolism and an increase in serum osteoprotegerin levels. These results suggest the involvement of osteoprotegerin in the pathogenesis of osteosclerosis associated with hematological malignancies

Polyclonal Immunoglobulin Recovery after Autologous Stem Cell Transplantation Is an Independent Prognostic Factor for Survival Outcome in Patients with Multiple Myeloma

We retrospectively analyzed multiple myeloma (MM) patients who underwent autologous stem cell transplantation (ASCT) without maintenance therapy to assess the impact of recovery of normal immunoglobulin (Ig) on clinical outcomes. The recovery of polyclonal Ig was defined as normalization of all values of serum IgG, IgA, and IgM 1 year after ASCT. Among 50 patients, 26 patients showed polyclonal Ig recovery; 14 patients were in &ge;complete response (CR) and 12 remained in non-CR after ASCT. The patients with Ig recovery exhibited a significantly better progression-free survival (PFS, median, 46.8 vs. 26.7 months, p = 0.0071) and overall survival (OS, median, not reached vs. 65.3 months, p &lt; 0.00001) compared with those without Ig recovery. The survival benefits of Ig recovery were similarly observed in &ge;CR patients (median OS, not reached vs. 80.5 months, p = 0.061) and non-CR patients (median OS, not reached vs. 53.2 months, p = 0.00016). Multivariate analysis revealed that non-CR and not all Ig recovery were independent prognostic factors for PFS (HR, 4.284, 95%CI (1.868&ndash;9.826), p = 0.00059; and HR, 2.804, 95%CI (1.334&ndash;5.896), p = 0.0065, respectively) and also for OS (HR, 8.245, 95%CI (1.528&ndash;44.47), p = 0.014; and HR, 36.55, 95%CI (3.942&ndash;338.8), p = 0.0015, respectively). Therefore, in addition to the depth of response, the recovery of polyclonal Ig after ASCT is a useful indicator especially for long-term outcome and might be considered to prevent overtreatment with maintenance therapy in transplanted patients with MM