Histological evidence for the cardiac safety of high-dose pegylated liposomal doxorubicin in a patient with HIV-associated Kaposi sarcoma: a case report and literature review.

BACKGROUND: Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear. CASE PRESENTATION: A 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient's left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2. CONCLUSIONS: This case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.

Peripherally inserted central catheter-related bloodstream infection due to Tsukamurella pulmonis: a case report and literature review.

BACKGROUND: Tsukamurella pulmonis is an aerobic gram-positive and rod-shaped organism that causes central catheter-related bloodstream infections in immunocompromised hosts. However, peripherally inserted central catheter (PICC)-related bloodstream infections due to this organism have not been reported. CASE PRESENTATION: We describe a case of a 48-year-old man with acquired immunodeficiency syndrome and diffuse large B cell lymphoma who received five courses of chemotherapy including rituximab , cyclophosphamide , doxorubicin hydrochloride , vincristine , and prednisone via a PICC. Five days after the last chemotherapy course, he presented with a high fever and shaking chills. His absolute neutrophil count was 4200/µL. Cultures obtained from blood and PICC culture revealed T. pulmonis. The colony count of T. pulmonis grown from PICC culture was 103 colony-forming units. Therefore, he was diagnosed with T. pulmonis bacteremia resulting from PICC-related bloodstream infection. The patient's condition improved and he became afebrile within 48 h after intravenous administration of cefozopran hydrochloride, which is a fourth generation cephalosporin. CONCLUSIONS: PICCs can be associated with T. pulmonis bacteremia, and fourth generation cephalosporins may be effective treatment.

Cutaneous invasive aspergillosis in a patient with glioblastoma receiving long-term temozolomide and corticosteroid therapy.

Glioblastoma is an aggressive brain tumor that requires multidisciplinary treatment including adjuvant radiotherapy, chemotherapy, and adjunct corticosteroids. Temozolomide is a commonly used chemotherapy drug and frequently causes lymphocytopenia. We describe the case of a 67-year-old woman with cutaneous invasive aspergillosis who had received long-term temozolomide and corticosteroid therapy for glioblastoma. She presented with multiple indurations, erythema, and purpura, some of which produced purulent discharge, in the anterior abdomen. Extensive intra- or inter-muscular abscesses of the right anterior abdominal wall were also observed. Her absolute lymphocyte counts were 156/µL on admission. Cultures obtained from the wound yielded Aspergillus fumigatus. She was diagnosed with secondary cutaneous invasive aspergillosis, which likely resulted from hematogenous dissemination. Although rare, this case illustrates that temozolomide-induced lymphocytopenia, especially in cases of concomitant corticosteroid use, can be associated with severe invasive aspergillosis.

Membranous nephropathy in an HIV-positive patient complicated with hepatitis B virus infection.

In ordinary settings, human immunodeficiency virus (HIV)-associated nephropathy should be considered when HIV infection is associated with heavy proteinuria. On the other hand, hepatitis B virus (HBV) may also play a role in the development of glomerular injury among patients with HIV infection, since HIV and HBV infections commonly occur together due to shared modes of transmission. We present here a case of nephrotic syndrome in an HIV-positive patient complicated with HBV infection. A renal biopsy revealed sparse granular deposits of immunoglobulin G in the subepithelial region, consistent with membranous nephropathy (MN) stage I. Moreover, immunostaining exhibited weak anti-hepatitis B core activity within glomeruli. These results led us to consider that HBV-associated MN might play a role in the development of nephrotic syndrome. Although anti-viral treatment for patients with HBV-associated MN has been suggested to be clinically effective, the use of two anti-HIV agents (tenofovir and emtricitabine), both of which have anti-HBV activities, was not effective for the patient's nephrotic syndrome, despite obtaining a decrease in the serum HBV-DNA levels. A lack of prospective data suggests that many decisions on the treatment of glomerulopathies with HIV infections are potentially empirical. Obviously, further studies and accumulated clinical experience are required to better determine the pathogenesis and management of HBV-associated MN among patients with HIV infections.

Non-surgical management of post-cesarean uterine infection with marked myometrial gas formation.

Gas in an infected organ generally indicates a severe infection, often requiring surgery; however, data are lacking as to post-cesarean gas-forming uterine infection. A 27-year-old Japanese primigravida underwent a difficult cesarean section, after which a high fever continued. Computed tomography (CT) revealed marked gas in the uterine anterior myometrium. Diagnosing this condition as post-cesarean uterine scar infection, we recommended surgical intervention, that is, hysterectomy or at least drainage; however, the patient refused it. Considering the patient's desire and lack of organ-failure signs, we employed intensive antibiotic treatment for 6 weeks. Serial CT indicated a gradual decrement in the gas amount and she recovered completely after 8 weeks. This case suggests that surgical procedure may not always be necessary for post-cesarean gas-forming uterine infection and CT may be useful to detect/follow this condition.

Hematopoietic recovery after administration of deferasirox for transfusional iron overload in a case of myelodysplastic syndrome.

Deferasirox (DFX) is a newly developed oral iron chelator that enables effective chelation with once daily administration. We describe here a case of transfusional-iron overloaded patient who experienced hematopoietic recovery after DFX administration. A 75-year-old woman with iron overload, who had been diagnosed with MDS (RCMD) and had received a transfusion of red blood cells and platelets regularly for 3 years, enrolled in the phase I clinical trial of ICL670 (DFX) in Japan. DFX administration steadily decreased her serum ferritin levels and chelated overloaded iron effectively. Interestingly, a year after initiation of the trial, she needed fewer blood transfusions, and no more transfusions after the 17th month of the trial. Even after suspending transfusions, her hemoglobin level and platelet count increased continuously, and she now has stable disease without blood transfusions. She has not received any specific treatment for MDS during this period. Examination of the bone marrow aspirates in the 35th month revealed dysplastic cells, indicating no remarkable change in the state of MDS. This case suggests that excess iron hampers hematopoiesis and that adequate iron chelation may improve hematological data in some iron-overloaded patients.

[Benefits of mycophenolate mofetil for refractory graft-versus-host disease].

We retrospectively evaluated the efficacy of mycophenolate mofetil (MMF) in the treatment of steroid-resistant acute and chronic graft-versus-host disease (GVHD) after hematopoietic stem cell transplantation. Thirteen patients, ten men and three women, consisted of 5 cases of acute myelogenous leukemia, 2 of acute lymphoblastic leukemia, 2 of chronic myelogenous leukemia, 2 of lymphoblastic lymphoma, and 1 case each of adult T-cell leukemia and peripheral T-cell lymphoma. The transfusions consisted of 5 peripheral blood, 7 bone marrow and 1 cord blood from 3 mothers, 4 siblings and 6 unrelated donors with conditioning treatments, including 8 total-body irradiation-based regimens, and 2 busulfan plus cyclophosphamide and 2 reduced-intensity regimens. GVHD prophylaxis included FK506 plus methotrexate (MTX) and/or antithymocyte globulin for 9 patients, and cyclosporine and MTX for 4 patients. All patients were treated with second-line MMF for steroid-refractory acute and/or chronic GVHD, and 11 patients improved. The adverse events were tolerable except for one patient in whom grade 3 neutropenia forced discontinuation of treatment. No case of non-relapse mortality occurred. We consider that MMF is beneficial and well tolerated for treatment of steroid-refractory GVHD.

Pleocytosis after hemopoietic stem cell transplantation.

Frequency and clinical significance of cerebrospinal fluid (CSF) pleocytosis in hemopoietic stem cell (HSC) transplantation were surveyed. Cyclosporine (CSA)- or tacrolimus (FK506)-based regimens were used as graft-vs-host disease (GVHD) prophylaxis in allogeneic HSC transplantation. CSF pleocytosis with or without neurologic symptoms was detected in 12 of 25 patients receiving allogeneic HSC transplants but in none of 11 patients receiving autologous HSC transplants. Of the 12 patients with CSF pleocytosis, only one patient developed leukoencephalopathy later. There was a correlation between CSF cell numbers and trough levels of CSA but not with those of FK506. In patients receiving allogeneic HSC transplants, CSF pleocytosis may be relatively common and may reflect neurologic damage associated with calcineurin inhibitors.

Retropharyngeal abscess due to methicillin-resistant Staphylococcus aureus in a case of acute myeloid leukemia.

We describe a case of acute myeloid leukemia (AML) complicated with retropharyngeal abscess (RPA) due to methicillin-resistant Staphylococcus aureus (MRSA) in a 56-year-old man. After administration of vancomycin and lavage of the retropharyngeal space with gentamicin, complete resolution of the RPA was observed. Despite their lower frequency, deep neck infections are associated with high mortality rates. The possibility of RPA should be considered in patients who present with fever, dysphagia and limitation of neck extension. Lavage of the retropharyngeal abscess with gentamicin may be optimal in cases of large RPA.

Usefulness of (18)F-Fluorodeoxyglucose-position emission tomography with computed tomography and gallium-67 scintigraphy for detection of Kaposi sarcoma lesions in a 40-year-old Japanese man with AIDS.

A 40-year-old Japanese man with acquired immunodeficiency syndrome was diagnosed with Kaposi sarcoma (KS) on the basis of the results of skin lesion biopsies. In addition, 18F-fluorodeoxyglucose-position emission tomography-computed tomography revealed abnormal fluorodeoxyglucose uptake in KS lesions, whereas gallium-67 scintigraphy did not show uptake of gallium. These findings indicate that combining these imaging modalities can help distinguish KS from other malignancies and opportunistic infections.

Massive immune hemolysis after non-myeloablative allogeneic peripheral blood stem cell transplantation with minor ABO-incompatibility.

A 35-year-old male, blood group B, Rh(D)+ type, received an allogeneic peripheral blood stem cell (PBSC) transplant after a non-myeloablative regimen of fludarabine and cyclophosphamide for resistant gammadelta cutaneous T-cell lymphoma (CTCL). The donor was his HLA-identical brother, blood group O, Rh(D)+ type. Graft-versus-host disease (GVHD) prophylaxis was performed with cyclosporine alone. On day +8, massive immune hemolysis occurred, followed by acute renal failure. Hemodialysis was performed eight times until recovery of renal function on day +24. The risk of delayed immune hemolysis after non-myeloablative allogeneic PBSC transplantation with minor ABO-incompatibility must be considered.

[Pseudomonas sepsis with ecthyma gangrenosum in an acute myeloid leukemia patient].

A 56-year-old woman with acute myeloid leukemia had two rapidly growing necrotizing nodules with ulcer formation on her head after the first course of consolidation therapy. Clinical features corresponding to sepsis (e.g., fever) appeared following the development of the skin lesion. Pseudomonas aeruginosa was isolated from the blood as well as pus of the lesion. Based on these findings, a diagnosis of ecthyma gangrenosum was made. Treatment with ciprofloxacin and gamma-globulin dramatically improved the patient's clinical features. Since Pseudomonas sepsis with ecthyma gangrenosum is associated with a high mortality rate, it is important to start immediate treatment with appropriate antibiotics.

Rituximab plus 70% cyclophosphamide, doxorubicin, vincristine and prednisone for Japanese patients with diffuse large B-cell lymphoma aged 70 years and older.

In the rituximab era, several large studies have suggested that full-dose rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) might be the best treatment for patients with diffuse large B-cell lymphoma (DLBCL) aged 60 years and older. However, it remains unclear whether this is also the case for those aged 70 years and older. Previously untreated patients with DLBCL aged 70 years and older (elderly) were treated with R-70%CHOP, and patients younger than 70 years (younger) were treated with full-dose R-CHOP every 3 weeks, for a total of 6-8 cycles. Complete remission (CR) rates in elderly versus younger patients were 75 vs. 78% (p = 0.7), respectively. The 3-year overall survival, event-free survival and progression-free survival of elderly versus younger patients were 58 vs. 78% (p < 0.05), 45 vs. 70% (p < 0.05) and 64 vs. 72% (p = 0.43), respectively. Severe adverse events were more frequent in the elderly, even with the dose reduction in that age group. Three-year PFS with R-70%CHOP for patients aged 70 years and older was not significantly worse than that with full-dose R-CHOP for younger patients, suggesting that R-70% CHOP might be a reasonable choice for patients with DLBCL aged 70 years and older, especially for those with comorbidities.

Correlation between flow cytometric identification of CD33-positive cells and morphological evaluation of myeloblasts in bone marrow of patients with acute myeloblastic leukemia.

Determination of the percentage of myeloblasts in bone marrow is important for the evaluation of acute myeloblastic leukemia (AML) and related disorders. Using flow cytometry with a CD45-blast gate (FCM/CD45), 226 bone marrow aspiration samples serially collected from 71 patients with de novo AML were analyzed. Bone marrow smears were evaluated independently by pathologists who did not know the corresponding flow cytometric data in advance. Patients received remission induction followed by consolidation. The CD33+ cell percentages evaluated by FCM/CD45 were strongly correlated to the myeloblast percentages determined by microscopic examination (r=0.8360, p<0.001). When only samples containing leukemic cells demonstrated by chromosomal or fluorescence in situ hybridization (FISH) analysis after induction were evaluated, positive correlations were found between CD33+ cell percentages determined by FCM/CD45 and myeloblast percentages determined by morphology (r=0.672, p<0.001). The identification of CD33+ cells by FCM/CD45 is useful for the evaluation of bone marrow myeloblasts in AML.

The usefulness of magnetic resonance imaging (MRI) for disseminated trichosporosis of the gastrocnemius muscles.

A 30-year-old man with acute myeloid leukemia who was pancytopenic after undergoing intensive chemotherapy developed pyrexia and severe pain of both lower legs. We immediately started empiric therapy with cefepime, vancomycin, and fluconazole for febrile neutropenia. However, symptoms progressed. After 4 days, Trichosporon was isolated from venous blood cultures. MRI showed hyperintense lesions within both gastrocnemius muscles and demonstrated reactive vasodilatation and interstitial tissue edema, thought to be induced by hyperpermeability of vessel membranes due to the local fungal infection. Amphotericin B was very effective against this organism. Trichosporosis is a rare infectious disease generally occurring in immunocompromized hosts. To the best of our knowledge, this is first reported case of bilateral Trichosporon infection of lower leg muscles. Severe leg pain was one of the most important signs of fungal infection in this patient with hematologic malignancy.

Autologous gamete cryopreservation before hemopoietic stem cell transplantation.

BACKGROUND: Infertility after hemopoietic stem cell transplantation (HST) is a serious problem for young patients. Autologous gamete collection before HST may be a promising strategy to overcome infertility. MATERIAL/METHODS: From October 1988 to December 2003, six male and nine female patients with hematological malignancies had autologous gametes collected before HST. The data on autologous gamete collection were analyzed. RESULTS: Sperm could be collected from three patients. However, in two of the three, the numbers and motility of the sperm were severely depleted because they received chemotherapy for one and 11 cycles, respectively. Normal sperm was only collected from one patient with myelodysplastic syndrome who had no history of receiving chemotherapy. One or more oocytes could be collected in five of nine female patients, although the five received multiple cycles of chemotherapy. The successful oocyte collection was associated with an ovulation stimulant. CONCLUSIONS: Autologous oocye collection before HST may be possible, even if patients receive multiple cycles of chemotherapy. In contrast, autologous sperm collection before HST may be difficult after patients receive chemotherapy. Successful pregnancy using autologous gametes after HST remains extremely difficult, especially in female patients; however, it is important to give information on infertility and autologous gamete collection to patients scheduled for HST.