Systemic inflammatory autoimmune disease before allogeneic hematopoietic stem cell transplantation is a risk factor for death in patients with myelodysplastic syndrome or chronic myelomonocytic leukemia.

Myelodysplastic syndrome (MDS) is well known to be complicated by systemic inflammatory autoimmune disease (SIADs). However, it remains unclear how the prognosis after allogenic hematopoietic stem cell transplantation (allo-HSCT) in patients with MDS is impacted by SIADs that occur before allo-HSCT. Therefore, we hypothesized that SIADs before allo-HSCT may be a risk factor for negative outcomes after allo-HSCT in patients with MDS. We conducted a single-center, retrospective, observational study of sixty-nine patients with MDS or chronic myelomonocytic leukemia who underwent their first allo-HCT. Fourteen of the patients had SIADs before allo-HSCT. In multivariate analysis, the presence of SIADs before allo-HSCT was an independent risk factor for overall survival (HR, 3.36, 95% confidence interval: 1.34-8.42, p = 0.009). Endothelial dysfunction syndrome was identified in five of 14 patients with SIADs who required immunosuppressive therapy or intensive chemotherapy, and notably, all patients with uncontrollable SIADs at allo-HSCT developed serious endothelial dysfunction syndrome and died in the early phase after allo-HSCT. The development of SIADs in the context of MDS is thought to reflect the degree of dysfunction of hematopoietic cells in MDS and suggests a higher risk of disease progression. In addition, MDS patients with SIADs before allo-HSCT are considered to be at higher risk of endothelial dysfunction syndrome because of preexisting vascular endothelial dysfunction due to SIADs. In conclusion, SIADs before allo-HSCT constitute an independent risk factor for death in MDS patients undergoing allo-HSCT.

A Case of IgG1-Lambda Multiple Myeloma With Hyperviscosity Syndrome and Cryoglobulinemia: Identification of the Subclass Fraction by Immunoelectrophoresis and Immunofixation Electrophoresis.

Hyperviscosity syndrome (HVS) is a complication of monoclonal plasma cell tumors. The frequency of HVS depends on the type of monoclonal protein. Immunoglobulin M (IgM) is more closely associated with HVS than IgG, and among IgG subclass monoclonal proteins, IgG3 is most frequently associated with HVS. We herein report a 44-year-old woman with multiple myeloma (MM), HVS, and cryoglobulinemia. Her monoclonal protein and cryoglobulin were IgG1-lambda (λ). She developed HVS at a lower monoclonal protein level because of the properties of the IgG1-derived monoclonal protein and cryoglobulin. Our case highlights the fact that identifying the IgG subclass is useful in predicting the risk of complicating HVS.

Ibrutinib Induces a Dramatic Improvement for Idiopathic Refractory Ascites Following Allogeneic Hematopoietic Cell Transplantation.

We herein report a case of idiopathic refractory ascites following allogeneic hematopoietic cell transplantation that was successfully treated with ibrutinib. A 39-year-old man presented with massive transudative ascites. Despite a high portal venous pressure, the liver histology showed traces of alloreactivity inconsistent with veno-occlusive disease/sinusoidal obstructive syndrome. Ibrutinib was administered for ascites possibly secondary to portal hypertension associated with the alloreactivity. The ascites dramatically improved, and the portal venous pressure was reduced. This case may help clarify the mechanism through which refractory ascites develops after allogeneic hematopoietic cell transplantation and establish appropriate treatment protocols.

[AL amyloidosis presenting with fluminant multiorgan failure accompanied by rapid progression from MGUS to multiple myeloma].

Monoclonal gammopathy of undermined significance (MGUS) is usually asymptomatic, and untreated follow-up is the standard treatment. However, MGUS progresses to multiple myeloma or related malignancy at a frequency of 1.5% per year. It is sometimes difficult to diagnose the progression of the disease via usual examinations. We herein report a case wherein rapid renal dysfunction led to a diagnosis of disease progression to multiple myeloma in a patient with MGUS that was asymptomatic for a long time. A 66-year-old woman developed rapid renal dysfunction requiring continuous hemodiafiltration 8 years after the diagnosis of IgA-κ type MGUS. A complete examination led to the diagnosis of IgA-κ type multiple myeloma. Chemotherapy was not effective, and she died due to sepsis on the 19th day of admission. A pathological autopsy revealed systemic amyloidosis and multiple abscesses positive for Staphylococcus aureus. An abnormal free light chain κ/λ ratio and M protein other than IgG are reportedly risk factors of disease progression of MGUS. In cases with these risk factors, it is important to always keep in mind the possibility of disease progression and to monitor the patient carefully for an early diagnosis.

Isoniazid-induced Immune Thrombocytopenia.

Drug-induced thrombocytopenia occurs through immune-mediated platelet destruction, and its management is challenging during tuberculosis treatment. Although rifampicin is the most common drug causing thrombocytopenia, isoniazid can also cause thrombocytopenia. We herein report a 75-year-old man who developed thrombocytopenia during tuberculosis treatment. Platelet-associated immunoglobulin G and a drug-induced lymphocyte stimulation test for isoniazid were positive; no other causes of thrombocytopenia were identified. The patient was diagnosed with isoniazid-induced immune thrombocytopenia, and the platelet count normalized after isoniazid discontinuation. We describe the immunological mechanism of thrombocytosis due to isoniazid, an uncommon cause of thrombocytopenia that physicians should be aware exists.