Y Tanaka

Long-term low-dose acyclovir against varicella-zoster virus reactivation after allogeneic hematopoietic stem cell transplantation

To evaluate the efficacy of long-term administration of acyclovir as prophylaxis against varicella-zoster virus (VZV) reactivation, we analyzed the medical records of 86 consecutive adult patients who obtained engraftment after allogeneic hematopoietic stem cell transplantation from January 1996 to March 2000. We started long-term low-dose (400 mg/day) oral administration of acyclovir in June 1999, and this was continued until the end of immunosuppressive therapy after transplantation. There was no breakthrough reactivation of VZV in patients receiving acyclovir. Five patients who were receiving cyclosporine or prednisolone developed VZV reactivation after discontinuing acyclovir. With this prophylaxis, the cumulative incidence of VZV reactivation at 1 year after transplantation decreased from 33% to 10% (P = 0.025). On multivariate analysis, the use of long-term acyclovir was identified as a significant independent parameter for the development of VZV reactivation. These findings suggest the efficacy of long-term prophylaxis with low-dose acyclovir. Resumption of acyclovir upon restarting immunosuppressive therapy might be important for the further prevention of VZV reactivation. The benefit of long-term low-dose acyclovir should be confirmed prospectively. Bone Marrow Transplantation (2001) 28, 689–692.

Increased soluble Fas-ligand in sera of bone marrow transplant recipients with acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) is a major complication following allogeneic bone marrow transplantation (BMT). Recently, accumulating evidence indicates that the Fas/Fas ligand (FasL) system is implicated in the pathogenesis of aGVHD in murine models. We determined the serum levels of soluble FasL (sFasL) in BMT recipients using an enzyme-linked immunosorbent assay. The serum sFasL was suppressed during the period of myelosuppression following the preparative regimen and subsequently increased with hematopoietic reconstitution after BMT. In patients with aGVHD, the serum sFasL level was significantly higher than in those without aGVHD. In the mixed lymphocyte reaction assay, sFasL in the supernatants was increased with a significant correlation to the level of 3H-thymidine uptake. Our findings suggest that the Fas/FasL system is activated by allogeneic stimulation and may have close correlation to the development of aGVHD in human BMT.

Reduced-intensity hematopoietic stem-cell transplantation for malignant lymphoma : a retrospective survey of 112 adult patients in Japan

Summary:We conducted a nation-wide survey of 112 adult Japanese patients who underwent reduced-intensity stem cell transplantation (RIST) from 1999 to 2002. Underlying diseases included indolent (n=45), aggressive (n=58) and highly aggressive lymphomas (n=9). Median age of the patients was 49 years. A total of 40 patients (36%) had relapsed diseases after autologous stem cell transplantation and 36 patients (32%) had received radiotherapy. RIST regimens were fludarabine-based (n=95), low-dose total body irradiation-based (n=6) and others (n=11). Cumulative incidences of grade II–IV acute graft-versus-host disease (GVHD) and chronic GVHD were, respectively, 49 and 59%. Cumulative incidences of progression and progression-free mortality were 18 and 25%, respectively. With a median follow-up of 23.9 months, 3-year overall survival rates were 59%. A multivariate analysis identified three significant factors for progression, which are history of radiation (relative risk (RR) 3.45, confidential interval (CI) 1.12–10.0, P=0.03), central nervous system involvement (RR 6.25, CI 2.08–20.0, P=0.001) and development of GVHD (RR 0.28, CI 0.090–0.86, P=0.026). RIST may have decreased the rate of transplant-related mortality, and GVHD may have induced a graft-versus-lymphoma effect. However, whether or not these potential benefits can be directly translated into improved patient survival should be evaluated in further studies.

Aspergillus tracheobronchitis after allogeneic bone marrow transplantation.

Recently Machidaet al presented in this journal a case of a patient with anAspergillus tracheobronchitis after allogeneic BMT together with a review of the literature of this serious complication after BMT. We would like to add our recent experience and comment on the role of galactomannan antigen testing in establishing the diagnosis of this Aspergillusinfection. A 56-year-old female patient underwent allogeneic BMT in our center after induction of first complete morphological and cytogenetic remission of acute myeloid leukemia. After conditioning with idarubicin, cyclophosphamide and busulfan, bone marrow-derived stem cells from her histocompatible sibling were infused. She developed grade II acute GVHD of the skin, for which she was treated with prednisone. Later on she experienced grade IV chronic GVHD of the gastro-intestinal tract and three episodes of CMVcolitis. Treatment with high-dose corticosteroids, cyclosporin, ganciclovir and CMV-hyperimmunoglobulins was given with limited success. On day 193 after BMT she was admitted to our hospital because of severe dyspnea, inspiratory wheezing and hoarseness. Temperature was not raised and persistent severe diarrhea was still present. Physical examination showed severe respiratory distress with use of accessory respiratory muscles and extreme inspiratory wheezing, and on auscultation her breath sounds were hardly audible. Chest X-ray and high-resolution CT scan were unremarkable. Lung function examination demonstrated extreme inspiratory and expiratory obstruction. Yellowish plaques, ulcerations and pseudomembranes were seen on bronchoscopy performed immediately and there were mucus plugs that almost completely obstructed the trachea and bronchi. Microscopic examination of the obstructing material showed hyphae and cultures yielded Aspergillus fumigatus . Biopsy was considered impossible because of the low platelet count. Daily bronchial flushing and treatment with high-dose amphotericin B (1 mg/kg/day, 45 mg daily) and nebulized amphotericin B was started with only temporary improvement. Liposomal amphotericin B 200 mg daily and itraconazole (200 mg, twice daily for 2 days, followed by 200 mg daily) as well as G-CSF (300 mg daily) were added without any improvement. Our patient became ventilator-dependent and could no longer cope with this regime. For this reason it was decided to abstain from further treatment and she died of respiratory failure the same day, 37 days after admission. Permission for autopsy was denied. Like Machidaet al we measured serum galactomannan antigen levels by ELISA (Platelia Aspergillus; Sanofi Diagnostics Pasteur, Marnes-la-Coquette, France). In a series of six consecutive serum samples, the highest galactomannan serum ratio found was 0.6 which is below the recommended cut-off level of 1.0. This observation might have several explanations. Firstly, Clarke et al divided fungal tracheobronchitis into two different morphological types. The first type is characterized by intraluminal growth involving the entire circumference of the airway with only superficial invasion and ulceration; tenacious mucus or

Transplantation for accidental acute high-dose total body neutron-and γ-radiation exposure

Accidental exposure to acute high-dose total body neutron radiation is rare. We report a 35-year-old man exposed to a total body dose of 5.4 Gy neutron- and 8.5–13 Gy γ-radiation in a radiation criticality accident. He received a blood stem cell transplant from his HLA-identical sister. There was bone marrow recovery with complete donor chimerism. Random chromatid breaks were observed in donor cells suggesting a bystander effect of neutron exposure. The subject died 82 days after the accident (75 days post transplant) from multi-organ failure.

Phimosis as a manifestation of chronic graft-versus-host disease after allogeneic bone marrow transplantation

Chronic GVHD is one of the major complications of BMT, involving a variety of organs, but rarely involving the genitourinary system. We report a patient who simultaneously developed extensive chronic GVHD and phimosis after BMT. From the clinical course and pathological findings, chronic GVHD was considered to be responsible for the phimosis. Despite intensive immunosuppressive therapy, the phimosis persisted. Phimosis is a rare complication after BMT, which may often remain neglected. Possibility of this complication should be considered in patients with chronic GVHD.

The mechanism for low yield of blood culture in invasive aspergillosis; the clinical importance of antigen detection tests revisited

The mechanism for low yield of blood culture in invasive aspergillosis; the clinical importance of antigen detection tests revisited

The limitation of circulating Aspergillus antigen detection methods for BMT recipients

In a recent issue of this journal, Bolwell et al reported the results of a randomized study comparing three strategies for administering G-CSF to patients submitted to autologous progenitor cell transplants. Seventy patients were randomized to receive G-CSF (5 mg/kg) starting either at days 0, 13 or 15. There was no difference in the outcome variables among the three groups. We would like to report a similar experience. Between March 1996 and March 1998 we performed 30 autologous peripheral blood progenitor cell transplantations. The underlying diseases were as follows: multiple myeloma (10), non-Hodgkin’s lymphoma (nine), Hodgkin’s disease (five) and breast cancer (six). Twenty-eight patients received G-CSF (5 mg/kg daily): the first 11 patients received G-CSF at day 11 (group one) and the other 17 patients received it at day 15 (group two). The two groups were well balanced with respect to the underlying diagnoses, age, conditioning regimens and the total number of CD34 cells infused. As shown in Table 1, there was no difference in the outcome variables between the two groups. The median duration of G-CSF use was 11 days (7–25) in group one and seven days (5–13) in group two (P = 0.007). The median duration of neutropenia was 10 days (6–14) in group one and nine days (5–20) in group two (P = 0.72). Likewise, the times to neutrophil and platelet engraftment were similar in both groups. The time to neutrophil engraftment was influenced by the number of CFU-GM and CD34 cells infused ( P = 0.03 for both comparisons, linear regression analysis). It is conceivable that G-CSF would confer an advantage

Expression pattern of PD-L1 and PD-L2 in classical Hodgkin lymphoma, primary mediastinal large B-cell lymphoma, and gray zone lymphoma

We aimed at investigating the relationship between classical Hodgkin lymphoma (cHL), primary mediastinal large B‐cell lymphoma (PMBL), and gray zone lymphoma (GZL) with intermediate characteristics between cHL and PMBL, from the perspective of the aberration in programed cell death 1 and the programed death ligands (PDLs) network.

Molluscum contagiosum infection after reduced-intensity cord blood transplantation

Cord blood transplantation is an attractive alternative forpatientswithhematologicmalignancieswhodonothaveamatchedrelatedorunrelateddonor.Thefeasibilityofcordblood transplantation using reduced-intensity regimens(reduced-intensity unrelated cord blood transplantation(RICBT)) for adult patients with hematologic diseases hasbeen reported.