Cytomegalovirus retinitis after allogeneic hematopoietic stem cell transplantation under cytomegalovirus antigenemia-guided active screening.

Although cytomegalovirus (CMV) remains a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT), the incidence of CMV retinitis is considered to be lower than the incidence of CMV infection in other organs following allogeneic HSCT. In this study, the incidence and characteristics of CMV retinitis were retrospectively evaluated in recipients of allogeneic HSCT. Ophthalmological screening was performed at the development of ocular symptoms or positive CMV infection using peripheral blood evaluated by pp65 antigenemia or polymerase chain reaction. Of the 514 patients, 13 patients developed CMV retinitis. The median onset of CMV retinitis was day 34 (range, 21-118) post transplant, and the cumulative incidence was 2.5% (95% CI, 1.6-4.2) at 6 months after transplantation. Five patients presented ocular symptoms at the onset. In the remaining eight asymptomatic patients, the diagnosis of CMV retinitis was made by the screening guided by positive CMV infection. All evaluable patients responded to antiviral treatment but three showed incomplete improvement with ocular sequela. Our results suggest that the incidence of CMV retinitis after allogeneic HSCT is not negligible and active ophthalmological screening based not only on symptoms but also positive CMV infection monitoring contributes to the early diagnosis of CMV retinitis.

Geriatric screening tools predict survival outcomes in older patients with diffuse large B cell lymphoma.

The proportion of elderly patients with diffuse large B cell lymphoma (DLBCL) appears to be increasing, with outcomes varying widely because of the patients' heterogeneity. Geriatric assessment is used to predict prognosis in elderly patients with DLBCL, but the utility of two simple screening tools for patients with DLBCL, the Flemish version of the Triage Risk Screening Tool (fTRST) and G8, has remained to be elucidated. We retrospectively assessed patients using fTRST and G8, and evaluated the impacts of the scores on survival outcomes in older patients with newly diagnosed DLBCL. A total of 59 patients aged 65 years or older and who were diagnosed with DLBCL were included. The median age was 77 years (range, 65-91 years), and the initial treatments were R-CHOP (63%) and R-THPCOP (31%). The estimated 2-year overall survival (OS) rate was significantly lower in patients with abnormal fTRST scores (≥ 2; N = 17) than in those with normal fTRST scores (< 2; N = 42): (50.5% (95% CI, 22.7-73.0%) vs. 82.2% (95% CI, 63.8-91.8%), P = 0.007). The estimated 2-year OS rate was significantly lower also in patients with abnormal G8 scores (≤ 14; N = 38) than in those with normal G8 scores (> 14; N = 21): (66.1% (95% CI, 46.7-79.5%) vs. 86.8% (95% CI, 55.7-96.7%), P = 0.03, respectively). These associations were independently significant after adjusting for other significant factors by multivariate analysis. These results suggest that the easy-to-use geriatric screening tools, fTRST and G8, have strong prognostic value for OS in older patients with DLBCL.

Successful treatment of breakthrough disseminated Trichosporon asahii fungemia in a patient with acute myeloid leukemia receiving itraconazole prophylaxis.

We encountered a case of a 73-year-old man with acute myeloid leukemia who developed Trichosporon asahii systemic infection while on itraconazole prophylaxis during severe neutropenia. Cryptococcal antigen was useful for diagnosis. Although itraconazole was ineffective in protecting against trichosporonosis, treatment was successful with voriconazole following liposomal amphotericin B.

Sinusitis caused by Exserohilum rostratum after cord blood transplantation for myelodysplastic syndrome: A case report and literature review.

Invasive fungal disease is a serious infectious complication of allogeneic hematopoietic stem cell transplantation (HSCT). Exserohilum rostratum is a species causing phaeohyphomycosis, which rarely causes invasive disease in humans. We treated a case of sinusitis caused by E. rostratum after cord blood transplantation (CBT). A 60-year-old man with myelodysplastic syndrome, who had a medical history of an operation to correct deviation of the nasal septum, developed sinusitis caused by E. rostratum under prolonged profound neutropenia after a second CBT because of the graft rejection of the first transplantation. Liposomal amphotericin B improved the sinusitis. A literature review revealed nine reported cases of sinusitis caused by E. rostratum, including our case. Although five cases had severe neutropenia at onset (HSCT recipients, n = 2; aplastic anemia, n = 3), the remaining four had no preexisting immunosuppressive conditions. However, three of the four patients had preexisting nasal diseases with or without a history of surgery, as in our case. Excluding our case, the outcome was fatal in five neutropenic patients, whereas the four patients without neutropenia recovered. Although sinusitis caused by E. rostratum is rare, E. rostratum should be recognized as a possible pathogen causing sinusitis in highly immunosuppressed patients such as HSCT recipients. Preexisting nasal disease and/or nasal surgery could be risks for this infection.

Allogeneic hematopoietic stem cell transplantation following treatment with brentuximab vedotin for refractory Hodgkin lymphoma.

Brentuximab vedotin (BV) is a novel agent used for the treatment of relapsed or refractory Hodgkin lymphoma. We have described two patients with refractory Hodgkin lymphoma, who were successfully treated with BV followed by allogeneic hematopoietic stem cell transplantation (HSCT). Although both patients were resistant to conventional chemotherapies, they responded to four or five doses of BV given every 3 weeks. Then, the patients underwent bone marrow transplantation from unrelated donors after reduced-intensity conditioning consisting of fludarabine and melphalan. They remained progression-free for more than 3 years after the transplantation. These findings suggest that BV could be a promising bridging therapy to curative allogeneic HSCT for relapsed or refractory Hodgkin lymphoma. Further accumulation of such cases is warranted to evaluate the efficacy and safety of BV therapy prior to allogeneic HSCT.

Hyponatremia associated with human herpesvirus-6 (HHV-6) encephalitis after allogeneic hematopoietic stem cell transplantation: A presentation different from HHV-6 myelitis.

Human herpesvirus-6 (HHV-6) encephalitis and myelitis following allogeneic hematopoietic stem cell transplantation (HSCT) is frequently life-threatening. We retrospectively evaluated the clinical significance of hyponatremia in cases of HHV-6 encephalitis/myelitis. Using an institutional database and medical records, we identified and retrospectively analyzed 16 cases of HHV-6 encephalitis and/or myelitis after allogeneic HSCT. HHV-6 encephalitis and myelitis were defined as the symptoms/signs with HHV-6-DNA in the cerebrospinal fluid. Seizure and memory disorder were defined as symptoms/signs of encephalitis, and dysesthesia and vesicorectal disorder as those of myelitis. Five patients developed encephalitis with or without myelitis, and 11 patients developed myelitis alone. Hyponatremia (median 129.1 mEq/L; range 125.9-130.1) was observed in all five patients with HHV-6 encephalitis at diagnosis, and values were significantly lower than those in patients with HHV-6 myelitis alone (median 137.6; range 134.0-142.2; P < 0.01). In three of the five patients with encephalitis, the decrease in sodium level preceded the clinical onset of encephalitis by one or two days. These results suggest that hyponatremia may be an important manifestation of HHV-6 encephalitis, but not of myelitis, and could be a useful tool for the early prediction or diagnosis of HHV-6 encephalitis.

Single-institutional retrospective analysis of Japanese patients with chronic lymphocytic leukemia.

Unlike in Western countries, chronic lymphocytic leukemia (CLL) is a rare lymphoid malignancy in Japan, and its clinical features remain to be elucidated in the Japanese population. Therefore, we retrospectively analyzed 29 Japanese CLL patients newly diagnosed at our institute. Seventeen (59%) were male, and their median age was 62 years. With a median follow-up period from diagnosis of 69 months (range, 3-170 months), 9 patients received some form of treatment for CLL. Three patients died of disease progression with or without infection (n=2) or skin cancer (n=1). Five-year overall and treatment-free survival rates were 83% (95%CI, 46-96%) and 67% (95%CI, 45-81%), respectively. Two patients received allogeneic hematopoietic stem cell transplantation for refractory disease, and both were alive without disease relapse at 53 and 110 months, respectively, after transplantation. These results suggest the clinical courses of Japanese patients with CLL to be comparable to those in Western countries. However, future studies of larger numbers of patients are needed to further elucidate the features and long-term clinical courses of CLL in the Japanese population.

Effects of calcineurin inhibitors on sodium excretion in recipients of allogeneic hematopoietic stem cell transplantation.

Calcineurin inhibitors (CIs) such as cyclosporine A (CSA) and tacrolimus often cause renal dysfunction, resulting in increased serum creatinine, hyperkalemia, and hyperuricemia. However, the effects of CIs on sodium excretion have not been fully elucidated. We retrospectively evaluated the effects of CI administration on sodium excretion in recipients of allogeneic hematopoietic stem cell transplantation (HSCT). Fifty consecutive recipients each of allogeneic HSCT receiving either CSA or tacrolimus (100 patients in total) with available data for weekly fractional excretion of sodium (FENa) for a 4-week period after transplantation were enrolled in this retrospective analysis. No significant differences in patient characteristics were observed between CSA and tacrolimus groups except for the type of donor. FENa was significantly higher at the 3rd (1.25 ± 0.80) and 4th weeks (1.53 ± 1.06) after transplantation as compared with that at the 1st week (0.93 ± 0.51; P < 0.01, P < 0.001, respectively) in the tacrolimus group, but not at any time point in the CSA group. In addition, FENa was significantly higher in the tacrolimus group than the CSA group at the 4th week (1.53 ± 1.06 vs. 1.13 ± 0.80; P < 0.05). These results suggest that tacrolimus increases sodium excretion after allogeneic HSCT, and that this effect is minimal with CSA.

Bacteremia due to Capnocytophaga species during chemotherapy-induced neutropenia in patients with hematological malignancies.

The number of reported cases of infections due to Capnocytophaga species (spp.) is limited. We herein describe four cases developing bacteremia due to Capnocytophaga spp. during neutropenia after chemotherapy for hematological malignancies. At the onset of bacteremia, 3 of the 4 patients had oral mucositis, and 2 were co-infected with other bacteria. Two patients developed bacteremia while receiving fluoroquinolone as prophylaxis against bacterial infection. Bacteremia resolved with administration of antimicrobial agents in all patients and no recurrences were observed thereafter. The emergence of fluoroquinolone-resistant or beta-lactamase-producing Capnocytophaga spp. has recently been reported. Therefore, Capnocytophaga spp. could be causative pathogens in breakthrough and refractory infections under fluoroquinolone prophylaxis and empiric therapy, respectively, for febrile neutropenia. Capnocytophaga spp. should be recognized as one of the causative pathogens of febrile neutropenia. Furthermore, accumulation of cases and susceptibility data are required to establish an optimal treatment protocol.

[Cellulitis due to Achromobacter xylosoxidans during bortezomib therapy for multiple myeloma].

Achromobacter xylosoxidans (A. xylosoxidans) is a non-fermentative gram-negative rod. This organism is reportedly a causative pathogen of bacteremia mainly in patients with hematological disorders. However, only one case of cellulitis due to A. xylosoxidans associated with hematological malignancy has been reported. An 80-year-old man developed cellulitis and subsequent bacteremia due to A. xylosoxidans during bortezomib therapy for multiple myeloma. Although his condition was serious enough to require intensive care, he fully recovered with appropriate antimicrobial agents and supportive care. The isolate was broadly resistant to antimicrobial agents, including cefepime, amikacin, and ciprofloxacin. Therefore, the identification and selection of appropriate antimicrobial agents were considered to have contributed to the successful outcome in this case. Physicians should recognize A. xylosoxidans as a possible pathogen causing cellulitis and secondary bacteremia, as well as being aware of its broad resistance to antimicrobial agents.

Outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for multiple myeloma.

We retrospectively evaluated single-institute outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with a reduced-intensity conditioning regimen consisting of fludarabine (125 mg/m²) and melphalan (140 mg/m²) for multiple myeloma. Twenty-three patients (median age: 46 years) were evaluated. Stem cell sources were bone marrow or peripheral blood stem cells from siblings (n = 4) and bone marrow from unrelated donors (n = 19). For graft-versus-host disease prophylaxis, cyclosporine A or tacrolimus with short-term methotrexate was given. Disease status at time of transplant was complete response in four patients, very good partial or partial response in 13, and stable or progressive disease in six. The median follow-up period of 7 survivors at analysis was 73.2 months (range 46.0-158.9 months). During the follow-up, disease recurrence or progression was observed in 21 patients, and was primary causes of death in 88% of the patients. The 5-year overall survival and progression-free survival rates were 38.6% (95% CI 19.3-57.7%) and 5.4% (95% CI 0.4-21.6%), respectively. Although allo-HSCT with this conditioning could be safely performed, further refinement of this approach aiming at more effective eradication of myeloma cells is clearly warranted.

[Bacteremia due to Rothia mucilaginosa after chemotherapy for myeloid malignancies].

The number of reported cases of bacteremia due to Rothia mucilaginosa (R. mucilaginosa), a component of the normal flora of human gastrointestinal tract mucosa, is limited. We encountered three cases of bacteremia due to R. mucilaginosa during neutropenia after chemotherapy for myeloid malignancies. Although all three patients were successfully treated with antimicrobial agents, one patient developed disseminated lesions in the lungs and soft tissue. The portal of R. mucilaginosa bacteremia is reportedly mucositis or dental disorders; however, no such complications were identified in our patients. Even in the absence of a preexisting portal, R. mucilaginosa should be recognized as a potential causative pathogen of bacteremia during neutropenic periods. Accumulations of cases and isolates are required to further elucidate the risk factors for developing R. mucilaginosa bacteremia, its clinical course, and the optimal antimicrobial treatment.

Immune-mediated Neuropathy with Anti-disialosyl IgM Antibodies in Diffuse Large B-cell Lymphoma: A Case Report and Literature Review.

A 36-year-old man with diffuse large B-cell lymphoma presented with polyneuropathy, and the diagnostic work-up revealed the presence of IgM antibodies against gangliosides with disialosyl residues (GD1b, GD3). He was treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone and received high-dose intravenous immunoglobulin for the treatment of neuropathy. After initiating the treatments, the patient's neurological impairment improved dramatically. He currently remains in complete remission without a flare-up of the polyneuropathy. Based upon our experience and other case reports of lymphoma with immune-mediated neuropathy caused by anti-disialosyl ganglioside IgM antibodies, we conclude that determining the anti-ganglioside antibody profile and beginning early treatment should be considered promptly for patients with malignant lymphoma who develop polyneuropathy.

Evaluation of safety and efficacy of transjugular liver biopsy in allogeneic hematopoietic stem cell transplant recipients.

We retrospectively evaluated the safety and utility of transjugular liver biopsy (TJLB) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Ten patients underwent HSCT between 1991 and 2013. Eight patients with thrombocytopenia received platelet transfusions before and/or during TJLB. No complications associated with TJLB were observed. Samples adequate for a pathological diagnosis were obtained in 9 of the 10 patients, and the diagnoses made by TJLB were graft-versus-host-disease in eight patients and non-specific hepatitis in one. These results suggest that TJLB is a safe and effective procedure for the evaluation of liver injury in HSCT recipients.

Efficacy of aprepitant in preventing nausea and vomiting due to high-dose melphalan-based conditioning for allogeneic hematopoietic stem cell transplantation.

High-dose melphalan has been gaining recognition as a highly emetogenic agent used in hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to elucidate the efficacy of aprepitant in preventing high-dose melphalan-induced emesis. Sixty patients who received melphalan (70 mg/m(2)/day, 2 days) and fludarabine (125 mg/m(2)/day, 5 days) as conditioning for allogeneic HSCT for hematological malignancies, and who received ondansetron and methylprednisolone as an antiemetic prophylaxis, were eligible. Twenty of these 60 patients also received aprepitant for 5 days (aprepitant group); the remaining 40 patients served as a control. The rates of complete response (CR), defined as no emesis without rescue medications, and complete protection (CP), defined as no emesis with or without rescue medications, were assessed between the two groups. The observation period was 12 days from the first day of melphalan administration. The CR and CP rates were significantly higher in the aprepitant group than in the control group during the observation period (35 % versus 10 %, P < 0.05; 85 % versus 33 %, P < 0.001; respectively). These results suggest that aprepitant in combination with ondansetron and steroid effectively ameliorates nausea and vomiting caused by the high-dose melphalan-based conditioning for allogeneic HSCT.

Validation of NIH consensus criteria for diagnosis and severity-grading of chronic graft-versus-host disease.

To validate the National Institutes of Health (NIH) consensus criteria for chronic GVHD, we retrospectively reviewed 143 patients who developed GVHD later than 100 days after allogeneic hematopoietic stem cell transplantation. Their GVHD was reclassified and the severity was graded according to the criteria. Only four patients (2.8 %) could not be reclassified into any type of GVHD. In the remaining 139 patients, reclassified subtypes were late acute GVHD in 52 patients (37.4 %), classic chronic GVHD in 33 (23.7 %), and overlap syndrome in 54 (38.8 %). Of 87 patients with classic chronic GVHD or overlap syndrome, the severity was graded as mild in 21 patients (24 %), moderate in 53 (61 %), and severe in 13 (15 %). The proportions of moderate (70 %) and severe (20 %) disease were significantly higher in patients with overlap syndrome than those with classic chronic GVHD (46 and 6 %, respectively; P < 0.001). Univariate and multivariate analyses of subtypes and severity did not identify any significant prognostic values in any of the transplant outcomes, such as transplant-related mortality, overall survival, GVHD-specific survival, or discontinuation of systemic immunosuppressants. These findings suggest that the NIH consensus criteria are useful for classification of chronic GVHD, but have limited significance in predicting clinical outcomes. The validity of these criteria remains inconclusive, and future prospective studies will be required to refine them.