Evaluation of the correlation between multiple organ calcification on CT and disease severity in patients with TAFRO syndrome.

PURPOSE: The purpose of this study was to investigate the incidence of multiple organ calcification and the correlation between multiple organ calcification and clinical severity in patients with thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly (TAFRO) syndrome. METHODS: We retrospectively identified 13 patients with TAFRO syndrome who were treated at our hospital between February 2019 and March 2021. Computed tomography (CT) images of TAFRO patients, which were acquired at admission and one month after admission, were evaluated. Additionally, clinical and laboratory data related to organ calcification and severity classification of TAFRO syndrome were investigated. The correlation between the presence of organ calcification on CT and TAFRO syndrome-severity classification was evaluated. RESULTS: One month after admission, calcification of the myocardium, adrenal glands, gallbladder wall, pancreas, kidney, skeletal muscle, and skin were observed in 38%, 46%, 15%, 15%, 15%, 23%, and 15% of the thirteen patients, respectively. The occurrence rate of calcifications in the myocardium, adrenal glands, and skeletal muscle was significantly higher in patients with a grade 4 or higher clinical severity than in those with a level up to grade 3 (p = 0.001, p = 0.005, and p = 0.035, respectively). CONCLUSIONS: Our results suggest that the higher the clinical severity in patients with TAFRO syndrome, the higher is the frequency of calcification in the myocardium, adrenal glands, and skeletal muscle; therefore, the assessment of these organ calcifications on CT images may be useful in predicting the severity of TAFRO syndrome.

Severe graft-versus-host disease of the lower intestinal tract after pomalidomide administration in a plasma cell leukemia patient following bone marrow transplantation.

Posttransplant treatment is performed to treat hematopoietic diseases but can lead to allogeneic-specific complications in addition to those seen in a non-transplant setting. Immunomodulatory drugs (IMiDs) activate cytotoxic T cells and suppress regulatory T cells. The optimal timing and optimal dose of IMiDs after allogeneic transplantation (allo-HSCT) to reduce complications and increase antitumor efficacy are difficult to determine because the degree of recovery of donor immune cells varies depending on the time after allo-HSCT. We experienced a patient with allo-HSCT who developed severe late acute graft-versus-host disease (GVHD) of the lower intestinal tract after receiving pomalidomide as a posttransplant therapy eight months after allo-HSCT. It is possible that pomalidomide induced acute GVHD by altering the activity of donor immune cells. This first case report highlights that the use of pomalidomide after allo-HSCT may lead to severe late acute GVHD. When pomalidomide is used after allo-HSCT, it is desirable to start with a small dose and gradually increase the dose while monitoring cytokine and lymphocyte subsets for the onset of GVHD.

Successful bridge therapy of gilteritinib to cord blood transplantation in relapsed acute myeloid leukemia after bone marrow transplantation.

The FMS-related tyrosine kinase 3 (FLT3) internal tandem duplication mutations (FLT3-ITD) positive acute myeloid leukemia (AML) is a disease with a dismal outcome. Gilteritinib is a second-generation FLT3 inhibitor with activity against ITD and high affinity toward the FLT3 receptor, thereby showing therapeutic potential for relapsed/refractory FLT3-mutated AML. Bone marrow transplantation (BMT) from a human leukocyte antigen (HLA) identical sibling donor was performed in a 38-year-old Japanese male with FLT3-ITD positive AML. Neutrophil engraftment (>0.5 × 109/L) was achieved on day 16, and bone marrow remission was revealed on day 32. The patient's AML relapsed hematologically four months after BMT and was resistant to salvage chemotherapy. Gilteritinib was administered and the patient achieved non-remission but 'stable disease' status according to the response criteria. During administration, liver damage was observed but controllable. The patient received cord blood transplantation (CBT) as the second hematopoietic stem cell transplantation (HSCT) three months after relapse and achieved second remission. There was no evidence of recurrence of AML four months after CBT. This case demonstrates that gilteritinib can control FLT3-ITD positive AML that relapsed early after initial HSCT and can bridge to second HSCT.

Concurrent immunoglobulin G-lambda type multiple myeloma and mixed cellularity classical Hodgkin lymphoma: A case report.

A 66-year-old man with a swollen right inguinal lymph node (LN) had pain on the lower side of the back. Computed tomography revealed bone disease in the back and swollen right inguinal LNs. Laboratory studies showed anemia and serum immunoglobulin G-lambda (IgG-λ) type monoclonal protein. The bone marrow contained 39.6% plasma cells. He was diagnosed with IgG-λ type multiple myeloma (MM). However, the pathological findings of the right inguinal LN were mixed cellular classical Hodgkin lymphoma (HL). The administration of melphalan, prednisone, and bortezomib (MPB) was started for MM; however, swelling in the right inguinal LN increased. After three cycles of MPB, the administration of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was started for HL. However, HL was refractory to ABVD. Pancytopenia subsequently progressed and rapid swelling occurred in his LNs. He died 7 months after diagnosis. Multiple myeloma was diagnosed, based on the typical symptoms, although the pathological findings of the LN indicated a diagnosis of HL. We analyzed the molecular relationship between MM and HL cells using a direct sequencing method. The sequencing results demonstrated that the variable-diversity-joining (VDJ) region of the IgH gene was identified with 94.4% of IGLV3-32*01 in the bone marrow sample at diagnosis. Furthermore, clonotypic IgH sequence was identified in CD30-positive cells from the LN. These results suggested that the clonal HL cells were derived from the same source as the clonal MM cells and demonstrated that MM and HL in this patient may have originated from the same B cell progenitor.

Clinical significance of cancer-related fatigue in multiple myeloma patients.

Cancer-related fatigue (CRF) is one of the adverse events in multiple myeloma (MM) patients treated with cytotoxic agents, proteasome inhibitors (PIs), and immunomodulatory drugs (IMiDs) such as bortezomib, lenalidomide, and thalidomide. The aims of our study were to prospectively analyze the clinical significance of CRF, and to evaluate the cumulative incidence of CRF and the survival rates of 16 MM patients who were treated with PIs and IMiDs. Reactivation of salivary human herpes virus (HHV)-6 and HHV-7 was analyzed using real-time quantitative polymerase chain reaction (qPCR). CRF was evaluated using a visual analog scale (VAS). Eleven newly diagnosed multiple myeloma (NDMM) and five relapsed or refractory MM patients were enrolled in this study. The cumulative incidence of CRF was 54.9%. The treatment types were not associated with the CRF incidence. The cumulative incidence of reactivation of HHV-6 and HHV-7 was 73.1% and 45.6%, respectively. However, the reactivation of HHV-6 and HHV-7 was not related to CRF. The overall survival (OS) and progression-free survival (PFS) in NDMM patients with CRF was significantly shorter than in those without CRF. In conclusion, CRF was one of the major symptoms in MM patients, and predicted shorter OS and PFS in NDMM patients.

Epstein-Barr Virus-associated Lymphoproliferative Disorder with Encephalitis Following Anti-thymocyte Globulin for Aplastic Anemia Resolved with Rituximab Therapy: A Case Report and Literature Review.

Epstein-Barr virus (EBV)-associated lymphoproliferative disorders (LPDs) sometimes occur following Anti-thymocyte globulin (ATG) administration for allogenic stem cell transplantation but are rare in aplastic anemia (AA) patients. A 55-year-old woman with AA following ATG developed refractory fever and was diagnosed with EBV-LPD. She was successfully treated with weekly rituximab monotherapy; however, she developed EBV encephalitis. She was admitted to the intensive care unit and finally recovered from unconsciousness. EBV-LPD should be considered after ATG for AA when symptoms appear. Because EBV-LPD following ATG for AA can rapidly progress, weekly monitoring of EBV-DNA and early intervention may be necessary.

Clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma.

The clinical features and prognostic significance of myeloma cells containing granules remain unclear. The purpose of this retrospective study was to investigate the clinical significance of granule-containing myeloma cells in patients with newly diagnosed multiple myeloma (NDMM). We retrospectively analyzed the records of 122 patients diagnosed with NDMM between January 2007 and December 2013. Granule-containing myeloma cells were defined as myeloma cells that exhibited three or more granules in their cytoplasm by May-Giemsa staining. The patients were classified into two groups, the granule-containing myeloma (GM) and nongranule-containing myeloma (non-GM) groups, depending on the proportion of myeloma cells that contained granules (cut-off value: 10%). There were 25 (20.5%) patients in the GM group. Patients in the GM group displayed significantly higher CD56 and CD49e expression than those in the non-GM group (t-test, P = 0.027 and 0.042). None of the patient characteristics differed significantly between the two groups. There was no significant difference in the chemotherapy profiles of the two groups, and the overall response rates of the two groups were similar. During the median follow-up period of 33.9 months, the overall survival (OS) in the GM group was similar to that in the non-GM group; 4-year OS of the GM and non-GM groups were 78.5% and 51.9%, respectively (P = 0.126). We concluded that cases of NDMM involving granule-containing myeloma cells are not infrequent. Moreover, CD56 and CD49e expression was significantly higher in the presence of myeloma cell populations, and the presence of granules did not affect survival.

Pharmacokinetics for once-daily modified release formulation of tacrolimus hydrate in unrelated hematopoietic stem cell transplantation.

A once-daily modified release formulation of oral tacrolimus (Tac QD) has been developed in response to the problem of nonadherence. However, there have been no data available about the efficacy of Tac QD conversion from intravenous Tac (Tac i.v.) in allogeneic hematopoietic stem cell transplantation (allo-SCT). We analyzed the pharmacokinetics (PK) of Tac QD in allo-SCT recipients. A total of 10 patients with hematological malignancies who received allo-SCT from unrelated donors were enrolled. Patients received Tac i.v. at 0.03 mg/kg a day before transplantation. Administration of Tac i.v. was converted to Tac QD at a 1:4 ratio when the patients had recovered from regimen-related gastrointestinal toxicity and could tolerate oral medication. After conversion, six out of 10 patients (60 %) showed a sustained decrease in Tac exposure and required dose adjustment. The conversion from Tac i.v. to Tac QD should be performed under close medical supervision. Area under the curve (AUC) and the trough of Tac QD showed a correlation, and the trough should be maintained above 7.5 ng/ml to provide an adequate AUC. Although four patients received bone marrow from an HLA DRB1 1 antigen-mismatched unrelated donor, no patients developed grade III-IV acute graft-versus-host disease (GVHD). The modification of Tac QD to maintain a whole-blood trough concentration above 7.5 ng/ml may be as effective as Tac BID.

Rapid progression and unusual premortal diagnosis of mucormycosis in patients with hematologic malignancies: analysis of eight patients.

Mucormycosis is a rare but emerging group of life-threatening opportunistic mycoses. We described experience of eight patients who developed mucormycosis. These patients had developed hematologic malignancies, and none achieved complete remission. Six of the eight patients presented with neutropenia, five received corticosteroid, and four had concomitant hyperglycemia. The most frequent physical finding was fever, and five patients complained of facial pain, headache, or chest pain. Four patients presented with concomitant bacterial infection, pulmonary aspergillosis, or intestinal candidiasis. Premortal diagnosis of mucormycosis was made in only one patient. Postmortem biopsy or autopsy was the diagnostic tool for the other patients. Although patients who were treated with amphotericin B survived longer than those treated with micafungin or voriconazole, all patients died due to the progression of mucormycosis. Estimated median survival was 23 days. Premortal diagnosis was rarely achieved as biopsy of infected tissues was the only diagnostic tool, and four patients who revealed dual infection were diagnosed with aspergillosis or bacterial infections. In patients with a high risk of mucormycosis presenting with pain and uncontrollable fever, mucormycosis should be included in the differential diagnosis. High dosages of liposomal amphotericin B should be given and surgical debridement should be performed promptly in cases highly suggestive of mucormycosis.

[Efficacy of CHOP+/-Rituximab-like therapy plus radiation therapy for patients with diffuse large B-cell lymphoma stage I].

Clinically, R-CHOP-like therapy plus radiation therapy is commonly performed for patients with limited stage diffuse large B-cell lymphoma. However, the efficacy and the safety of the management have not been evaluated properly. In particular, we have few definitive reports about patients with stage I DLBCL. This time we evaluated the effect of CHOP+/-R-like therapy plus radiation therapy, by analyzing 28 patients with stage I DLBCL, retrospectively. 15 patients were treated with the RCHOP-like therapy, and 13 received CHOP-like therapy combined with radiation therapy. A complete response was observed in all of the patients. With a median follow-up time of 14 months, 1-year progression-free survival (PFS) was 100%, and the 1-year overall survival (OS) was 100% for the patients receiving the R-CHOP-like therapy. With a median follow-up time of 68 months, 5-year PFS was 84. 6%, and 5-year OS was 100% for patients receiving the CHOP-like therapy. Since the followup time was not enough and the patient numbers were too few, the benefit of the addition of Rituximab to the CHOP therapy could not be clarified. We need to assess the safety and the efficacy of the combined modality therapy for patients with limited-stage DLBCL by a larger prospective study.

Gemtuzumab ozogamicin (GO) in relapsed/refractory patients with acute myeloid leukemia.

OBJECTIVE: Gemtuzumab ozogamicin (GO) is a humanized anti-CD33 antibody, linked to calicheamicin, which has been approved in Japan recently. We conducted to evaluate the efficacy and toxicity of GO in our patients with relapsed or refractory AML retrospectively. PATIENTS AND METHODS: Data were collected between March 1, 2000, and March 1, 2006, on 10 patients with relapsed or refractory AML(excluding FAB: M3). Scheduled treatment was two doses of GO monotherapy, 14-28 days apart. RESULTS: Of the 10 assessable patients, two patients achieved CR. CR duration of one patient lasted for 52 months with post-remission treatment. Grade 4 neutropenia occurred in 9 patients, and the incidence of grade 3 or 4 thrombocytopenia was 100%, with no severe bleeding events. Two patients developed infusion-related adverse events that included grade 3 allergic reaction with shock status. Liver damage (grade 3 or 4) were observed in 40% of patients after GO treatment. No patient developed hepatic veno-occlusive disease including 2 patients who underwent HSCT. CONCLUSION: GO is a valuable new treatment option for relapsed or refractory AML patients, however, the benefit from single agent appears insufficient. On going clinical trials including combination with other antileukemic agents might better define the role of GO.