Ponatinib (PON) is a key drug for patients with second tyrosine kinase inhibitor (TKI)-resistant/intolerant Philadelphia chromosome-positive leukemia (Ph+ leukemia); however, the occurrence of vascular adverse events (VAEs) in patients treated with PON should be carefully monitored. A retrospective analysis involving seven patients treated with PON was conducted to elucidate the incidence rate and risk factor for the development of VAEs. In the present study, risk assessment and monitoring of VAEs were performed using SCORE Risk Chart and Suita Score (10-year risk for fatal cardiovascular event), respectively. Despite the prophylactic use of aspirin, cerebral infarction and unstable angina occurred in two patients. By contrast, deep vein thrombosis did not improve in a patient treated with edoxaban. Our data suggest that patients with Ph+ leukemia possessing risk factors, medical history of lifestyle diseases, and administration of long-term second TKI treatment require careful monitoring of VAEs and therapeutic intervention to lifestyle diseases.

In 2003, a 60-year-old man presenting with thrombocytosis was referred to our hospital. Laboratory tests revealed normal white blood cell count and hemoglobin level. Bone marrow examination showed an increased number of megakaryocytes with dysplasia. G-banded karyotype analysis revealed del (5q). Initially, the patient was diagnosed with myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and it was treated with aspirin and hydroxyurea. During the treatment course, fluorescence in situ hybridization for CSF1R and EGR1 was performed to detect del (5q), which showed negative results. In 2017, the patient had increased platelet count despite receiving treatment. A comprehensive genomic profiling revealed that the deleted region in this case was present in 5q14-5q23, which was different from the common deleted region of 5q− syndrome (5q32-5q33, where CSF1R was present) and that of high-risk MDS or acute myeloid leukemia (5q31, where EGR1 was present). Moreover, a CALR mutation was also detected. This case met the diagnostic criteria of essential thrombocythemia. The platelet count decreased with the administration of anagrelide. In conclusion, comprehensive genetic profiling is very important, and it leads to accurate diagnosis and therapy.

Although elotuzumab (ELO) is associated with improved outcomes in patients with relapsed/refractory multiple myeloma (MM), no data are available for the usage of ELO following allogeneic stem cell transplantation (allo-SCT). Here, we report two cases of relapsed MM treated with ELO in combination with lenalidomide (LEN) and dexamethasone (ELd) following allo-SCT. Case 1 had been treated with 11 lines of therapy followed by cord blood transplantation resulting in partial response. ELd was introduced 140 days post-transplantation and continued for eight cycles until disease progression. No worsening in graft-versus-host disease (GvHD) was observed under ELd treatment. Case 2 had received unrelated bone marrow transplantation due to primary refractory disease after undergoing six regimens. Carfilzomib-based maintenance therapy had to be discontinued owing to severe myelosuppression. Subsequently, ELd treatment was initiated 544 days following the allo-SCT, which led to an improvement in serum paraprotein level and amelioration in GvHD. In both cases, immunosuppressants were tapered off. Several studies have shown exacerbation of GvHD under LEN monotherapy following allo-SCT. However, an ELd regimen may be one of the safer options for treating post-allo-SCT relapse.

A 47-year-old man with acute myeloid leukemia and myelodysplastic-related changes relapsed after an allogenic bone marrow transplant and received a cord blood transplant as salvage therapy. The patient developed febrile neutropenia that was resistant to broad-spectrum antibiotics and multiple, painful, nodular skin lesions on his trunk and extremities before engraftment. A skin biopsy and blood culture found mold, and the subsequent microscopic examination, mass spectrometry, and DNA sequencing of the fungal colonies identified Fusarium solani. The patient's fever and skin lesions began to improve with the administration of liposomal amphotericin B at 5 mg/kg/day. Neutrophilic engraftment occurred on day 19. Stage 3 acute skin graft-versus-host disease was cured by the application of topical steroid. Unexpectedly, a change from liposomal amphotericin B to voriconazole on day 38 exacerbated the Fusarium infection. The Fusarium infection was finally cured by the administration of liposomal amphotericin B for a total of 19 weeks. Neutrophilic engraftment, an immediate definitive diagnosis, the sufficient and long-term administration of appropriate antifungal medication, and avoidance of the systemic administration of steroids might have contributed to the successful outcome of this patient.

A 69-year-old woman presented to National Defense Medical College hospital for suspected nephrotic syndrome due to weight gain of 30 kg in 3 weeks and bilateral lower leg edema. However, her urinalysis showed microproteinuria, which excluded nephrotic syndrome. Computed tomography revealed severe systemic edema, pleural effusion, ascites, and enlarged cervical and axillary lymph nodes. Histological examination of axillary lymph node specimen showed a typical architecture of angioimmunoblastic T-cell lymphoma. One course of CHOP chemotherapy regimen was administered which improved the lymph nodes and systemic edema. The patient achieved complete remission after 6 courses of CHOP. Because serum vascular endothelial growth factor (VEGF) level was elevated before the treatment and normalized after the treatment, increased vascular permeability mediated by VEGF was hypothesized to have caused the systemic edema. In addition, VEGF secretion from Epstein-Barr virus (EBV)-infected cells was likely associated with the patient's clinical condition because B lymphocytes stained with CD20 were positive for Epstein-Barr virus-encoded small RNAs (EBERs) and VEGF.

A 70-year-old female was initially diagnosed with acute myeloid leukemia (AML) and achieved complete remission by conventional chemotherapy. She presented with leukocytosis and pleural effusion six years later, and was diagnosed with myelodysplastic/myeloproliferative neoplasms (MDS/MPN) by bone marrow (BM) analysis. Pyrexia and lymphadenopathy developed one year later, and lymph node biopsy confirmed peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS). Chemotherapy achieved a partial remission. Fifty-two days after her last chemotherapy treatment, increased blasts in the peripheral blood along with marked lymphadenopathy were observed, which were considered to be indicative of the simultaneous development of AML and lymphoma. TET2 mutations were confirmed in BM and lymph node samples. Development of AML and PTCL-NOS might be due to clonal hematopoiesis associated with aging and chemotherapy.

A 71-year-old male developed plasmacytoma on September 2015. He received radiotherapy, followed by posterior spinal fusion, at Th5 and L3 and was subsequently administered lenalidomide plus dexamethasone (Ld) from January 2016. After the 9th course of Ld, the patient complained of epigastric discomfort and papules on the face. FDG-PET showed duodenum 3rd potion and indicated nodular lesions with high glucose uptake on the lower lobe of the right lung and third portion of the duodenum. Biopsy of the skin, duodenum, and lung revealed Grocott's stain positive circular bodies, and the patient was subsequently diagnosed with disseminated cryptococcosis. Although disseminated cryptococcosis often causes encephalomeningitis, gastrointestinal involvement is rarely reported. The underlying conditions of disseminated cryptococcosis include AIDS, hematological malignancies, and steroid and immunosuppressant use. The sites of infections are the esophagus, stomach, small intestine, and colon. Disseminated cryptococcosis is diagnosed by abdominal pain, bloody stool, and gastrointestinal perforation. However, disseminated cryptococcosis may be asymptomatic; therefore, it is imperative that there is no delay in its diagnosis.

A 65-year-old man with multiple lymphadenopathy presented to our hospital and was diagnosed with StageIVA blastoid-variant mantle cell lymphoma (MCL), with a Ki-67 index of 93%. Partial response was achieved after four courses of CHASER (cyclophosphamide, cytarabine, dexamethasone, etoposide, and rituximab) chemotherapy, and complete response was achieved after autologous stem cell transplantation (ASCT). Six months after ASCT, the MCL relapsed with occurrence of tumors one on the left upper arm and one in the cerebrum, which were proved to be resistant to the conventional chemotherapy and progressed rapidly. These tumors disappeared with scarring following the local irradiation (45 Gy). However, the unirradiated regions became enlarged. The bulky abdominal lesion was treated with local irradiation (41 Gy) combined with 560 mg of ibrutinib but still resulted in progressive disease 1 month after initiating the ibrutinib treatment. Finally, the patient died 5 months post-relapse. The prognosis of patients with blastoid-variant MCL with high Ki-67 index is extremely poor. Furthermore, the risk of central nervous system (CNS) involvement is very high. Therefore, ibrutinib maintenance therapy post ASCT might be a treatment option to prevent CNS involvement. Further efforts might be needed to improve the outcomes of blastoid-variant MCL with a high Ki-67 index.

The rare chromosomal translocation t(16;21) has been associated with CD56 expression and extramedullary lesions in acute myeloid leukemia (AML). We herein report the first case of the development of isolated pericardial relapse after HLA-haploidentical peripheral blood stem cell transplantation (haplo-PBSCT). A 42-year-old male AML patient with t(16;21)(p11.2;q22) received haplo-PBSCT at partial remission, and he exhibited dyspnea due to massive pericardial effusion 11 months later. The effusion analysis revealed CD56+ leukemic cells, and G-banded karyotyping of the cells demonstrated t(16;21)(p11.2;q22). Salvage chemotherapy was administered, but only a transient improvement of the effusion was achieved. Moreover, the pleural effusion developed without bone marrow relapse.

An 84-year-old woman presented pancytopenia. She was diagnosed with myelodysplastic syndromes (MDS) with excess blasts-1, however, she declined treatment with azacitidine (AZA). Ten months later, bilaterally symmetrical, non-pitting edema appeared on the lower legs. A skin biopsy of the lower leg revealed lymphedema. The appearance and location of the lymphedema suggested an immunologic etiology; however, tests for autoimmune diseases yielded negative results. Therefore, a relationship between MDS and lymphedema was, therefore, speculated. Consequently, treatment with AZA was started, which led to marked improvement in both the lymphedema and pancytopenia. Based on the skin tissue pathology and the improvement in MDS after treatment with AZA, MDS-related autoinflammatory lymphedema was diagnosed.