Nocardiosis in transplant recipients

Nocardiosis is a rare opportunistic infection caused by Nocardia spp., an aerobic actinomycete, that mainly affects patients with cell-mediated immunity defects, such as transplant recipients. Despite recent progress regarding Nocardia identification and changes in taxonomic assignment, many challenges remain for the diagnosis or management of nocardiosis. This opportunistic infection affects 0.04 to 3.5 % of patients with solid organ or hematopoietic stem cell transplantation, depending on the organ transplanted, cytomegalovirus (CMV) infection, corticosteroids dose and calcineurin inhibitors level. Nocardiosis diagnosis relies on appropriate clinical, radiological and microbiological workup that includes the sampling of an accessible involved site and molecular microbiology tools. In parallel, extensive clinical and radiological evaluations are mandatory, including brain imaging, even in the absence of neurological signs. In transplanted patients, differential diagnosis is challenging, with co-infections reported in 20 to 64 % of cases. As the antibiotic susceptibility pattern varies among species, the antimicrobial regimen before species identification should rely on the association of antibiotics active on all species of Nocardia. Bactericidal antibiotics are required in cases of severe or disseminated disease. Furthermore, in transplant recipients, combination therapy is difficult to manage because of cumulative toxicity and interactions with immunosuppressive agents. Because of a high recurrence rate, antibiotic therapy should be prescribed for 6 to 12 months.     

Atypical Strain of Toxoplasma gondii Causing Fatal Reactivation after Hematopoietic Stem Cell Transplantion in a Patient with an Underlying Immunological Deficiency

In immunocompromized patients, including hematopoietic stem cell transplant (HSCT) recipients, life-threatening toxoplasmosis may result from reactivation of previous infection. We report a case of severe disseminated toxoplasmosis that developed early after allogeneic HSCT for T-cell lymphoblastic leukemia/lymphoma in a 15-year-old Toxoplasma gondii-seropositive boy with Nijmegen breakage syndrome, a rare genetic DNA repair disorder associated with immunodeficiency. The donor was the patient''s HLA-identical brother. Prophylaxis with cotrimoxazole was discontinued a day before the HSCT procedure. Signs of lung infection appeared as early as day 14 post-HSCT. The presence of tachyzoite-like structures on Giemsa-stained bronchoalveolar lavage (BAL) fluid smears suggested toxoplasmosis. Real-time PCR targeted at the T. gondii {"type":"entrez-nucleotide","attrs":{"text":"AF146527","term_id":"5916167","term_text":"AF146527"}}AF146527 gene revealed extremely high parasite burdens in both blood and BAL fluid. Although immediate introduction of specific treatment resulted in a marked reduction of the parasite load and transient clinical improvement, the patient deteriorated and died of multiple organ failure on day 39 post-HSCT. Direct genotyping of T. gondii DNA from blood and BAL fluid with the PCR-restriction fragment length polymorphism method revealed type II alleles with SAG1, SAG2, and GRA6 markers but alleles of both type I and type II with GRA7. Additional analysis with 15 microsatellite markers showed that the T. gondii DNA was atypical and genetically divergent from that of the clonal type I, II, and III strains. This is the first report of increased clinical severity of toxoplasmosis associated with an atypical strain in the setting of immunosuppression, which emphasizes the need to diagnose and monitor toxoplasmosis by quantitative molecular methods in cases of reactivation risk.     

Cerebral Toxoplasmosis After Autologous Peripheral Blood Stem Cell Transplantation

Toxoplasmosis appears to be a rare opportunistic protozoal infection following haematopoietic stem cell transplantation (HSCT). Most cases have been reported in allogeneic HSCT recipients, with only anecdotal reports of infection occurring after autologous transplantation. Reported here is the case of a patient who developed cerebral toxoplasmosis following autologous peripheral blood stem cell transplantation for non-Hodgkin's lymphoma.     

Detection of toxoplasmosis in patients with end-stage renal disease by enzyme-linked immunosorbent assay and polymerase chain reaction methods

Toxoplasmosis caused by Toxoplasma gondii is an opportunistic infection. In healthy individuals, the infection is largely asymptomatic, but in immunocompromised people the parasite can become widely disseminated, causing severe toxoplasmosis. In patients undergoing haemodialysis, the phagocytic process shows a highly significant impairment. Therefore, this study aimed to investigate toxoplasmosis in patients with end-stage renal disease (ESRD) undergoing haemodialysis in Ahvaz hospitals, southwest of Iran. A total of 280 patients and 100 healthy subjects participated in this study. The presence of serum IgM and IgG antibodies against T. gondii was detected by ELISA and the presence of Toxoplasma parasites in whole blood was evaluated by GRA6 PCR. Anti-T. gondii IgG antibodies were detected in 82 (29.3 %) haemodialysis patients and 26 (26 %) controls. In addition, anti-T. gondii IgM antibodies were detected in 7.9 % of patients and in 4 % of controls. For both the antibodies, the differences were statistically significant (P?<?0.05). PCR was performed with DNA extracted from blood samples of all patients and controls. PCR gave positive results with four of the 280 blood samples from patients but none for the control blood samples. The results revealed a high percentage of positivity for Toxoplasma antibodies in patients with ESRD undergoing haemodialysis and also confirmed the parasite in whole blood, indicating disseminated infection in these patients. Patients undergoing dialysis have a higher rate of active infection with Toxoplasma likely due to reactivation of a chronic infection. Thus, parasitological examinations of ESRD patients should be periodically carried out for monitoring and evaluating the possible dissemination of toxoplasmosis during haemodialysis.     

Molecular Diagnosis of Toxoplasmosis in Immunocompromised Patients: a 3-Year Multicenter Retrospective Study

Toxoplasmosis is a life-threatening infection in immunocompromised patients (ICPs). The definitive diagnosis relies on parasite DNA detection, but little is known about the incidence and burden of disease in HIV-negative patients. A 3-year retrospective study was conducted in 15 reference laboratories from the network of the French National Reference Center for Toxoplasmosis, in order to record the frequency of Toxoplasma gondii DNA detection in ICPs and to review the molecular methods used for diagnosis and the prevention measures implemented in transplant patients. During the study period, of 31,640 PCRs performed on samples from ICPs, 610 were positive (323 patients). Blood (n = 337 samples), cerebrospinal fluid (n = 101 samples), and aqueous humor (n = 100 samples) were more frequently positive. Chemoprophylaxis schemes in transplant patients differed between centers. PCR follow-up of allogeneic hematopoietic stem cell transplant (allo-HSCT) patients was implemented in 8/15 centers. Data from 180 patients (13 centers) were further analyzed regarding clinical setting and outcome. Only 68/180 (38%) patients were HIV⁺; the remaining 62% consisted of 72 HSCT, 14 solid organ transplant, and 26 miscellaneous immunodeficiency patients. Cerebral toxoplasmosis and disseminated toxoplasmosis were most frequently observed in HIV and transplant patients, respectively. Of 72 allo-HSCT patients with a positive PCR result, 23 were asymptomatic; all were diagnosed in centers performing systematic blood PCR follow-up, and they received specific treatment. Overall survival of allo-HSCT patients at 2 months was better in centers with PCR follow-up than in other centers (P < 0.01). This study provides updated data on the frequency of toxoplasmosis in HIV-negative ICPs and suggests that regular PCR follow-up of allo-HSCT patients could guide preemptive treatment and improve outcome.     

Correlation of Parasite Load Determined by Quantitative PCR to Clinical Outcome in a Heart Transplant Patient with Disseminated Toxoplasmosis

Disseminated toxoplasmosis is a life-threatening infection in transplant recipients, which results either from reactivation of latent infection or from organ-transmitted primary infection. Preventive measures and diagnostic screening methods differ between countries and are related to the seroprevalence of Toxoplasma spp. in the general population. Here we report a case of disseminated toxoplasmosis in a heart transplant recipient with previous immunity that occurred after cotrimoxazole prophylaxis for the prevention of Pneumocystis jirovecii pneumonia was stopped. Quantitative PCR proved useful for the diagnosis and monitoring of Toxoplasma infection. Decreasing parasitic burdens in sequential samples of cerebrospinal fluid, blood, and bronchoalveolar lavage fluid correlated with a favorable outcome and allowed modulation of the immunosuppressive drug regimen. The duration of anti-Toxoplasma treatment and the need for maintenance prophylaxis are discussed, as well as prophylaxis for solid-organ transplant recipients. Although a rare event in heart transplant recipients, Toxoplasma reactivation must be investigated promptly, since early treatment improves the prognosis.Toxoplasmosis is a worldwide parasitic disease caused by the intracellular protozoan Toxoplasma gondii. After infection, acquired mostly through contaminated vegetables or undercooked meat, the parasite can persist for life, encysted in different sites such as the muscles, heart, brain, eye, and, more rarely, other organs. Whereas clinical symptoms are usually absent or mild in primarily infected immunocompetent individuals, the infection is life-threatening for immunocompromised patients (17). In transplant patients, severe or disseminated toxoplasmosis can result either from reactivation of latent infection in the recipient or from organ-transmitted infection from a seropositive donor to a seronegative recipient (6, 29), a situation where heart transplants carry the highest risk (16, 19, 22, 32). Reactivation of a chronic infection may occur in the recipient irrespective of the type of graft, but the risk is closely related to the duration and degree of immunosuppression. The risk also differs according to the immunosuppression protocol and therefore according to the graft, with hematopoietic stem cell transplantation (HSCT) carrying the highest risk (10). Furthermore, the incidence of Toxoplasma reactivation is greater in countries with higher seroprevalences. The diagnosis of acute toxoplasmosis in immunocompromised patients relies on PCR detection of parasite DNA in blood, cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) samples, or biopsy specimens. Serology performs poorly in the diagnosis of reactivation of infection, due to a lack of sensitivity (in HSCT patients) or poor correlation with clinical reactivation (for solid-organ transplantation [SOT]).Here we report a case of disseminated toxoplasmosis in a previously seropositive heart transplant recipient who underwent several severe infectious complications leading to interruption of cotrimoxazole prophylaxis and subsequently to Toxoplasma reactivation. After the initial diagnosis, the infection was monitored by quantitative PCR on blood, CSF, and pulmonary samples. A decrease in parasite load correlated with a favorable clinical outcome upon treatment. Quantitative PCR is considered to be a valuable tool for the diagnosis and monitoring of acute toxoplasmosis in SOT recipients. Our results reemphasize the need to monitor Toxoplasma reactivation in seropositive recipients, particularly in countries with high seroprevalences. Potential drug regimens for anti-Toxoplasma chemoprophylaxis in heart transplant patients are discussed.     

Two Cases of Nocardia bacteraemia in Solid Organ Transplant Recipients

Nocardiosis is an opportunistic infection occurring in immunosuppressed patients. While disseminated nocardiosis is common in immunosuppressed patients, Nocardia bacteraemia is rare. There are few reports of Nocardia bacteraemia following solid organ transplantation. We report two cases of Nocardia bacteraemia in solid organ transplant recipients-Nocardia cyriacigeorgica bacteraemia in liver transplant recipient and concomitant Nocardia farcinica bacteraemia and cyclosporiasis in a heart transplant recipient. Prompt recognition of early bacteraemia with initiation of antibiotic therapy may avoid the complications of disseminated disease in the solid organ transplant recipients.     

Risk of reactivated toxoplasmosis in haematopoietic stem cell transplant recipients: a prospective cohort study in a setting withholding prophylaxis

ObjectivesReactivation of latent toxoplasmosis may be life-threatening in haematopoietic stem cell transplant (HSCT) recipients. We conducted an 8-year-long prospective study on the diagnosis and monitoring of reactivated toxoplasmosis in paediatric HSCT recipients. The primary objective was to determine the incidence of reactivated toxoplasmosis in a setting that withholds prophylaxis until engraftment. The second objective was to identify the subgroups of HSCT recipients particularly prone to reactivation who may benefit the most from regular PCR follow-up.MethodsSerological and qPCR screening targeting the Toxoplasma 529 bp gene was performed before HSCT, and continued by weekly monitoring after HSCT for a median time of 104 days.ResultsReactivated toxoplasmosis was diagnosed in 21/104 (20.2%), predominantly in allo- (19/75) and rarely in auto-HSCT (2/29) recipients. Over 50% (14/21) of cases were diagnosed during the first month after HSCT, while awaiting engraftment without prophylaxis. Toxoplasma disease evolved in only three (14.3%, 3/21) patients, all treated by allo-HSCT. Reactivation was more frequent in patients treated for acute lymphoblastic leukaemia (3/27, p 0.03) and especially, in recipients of haploidentical stem cells (10/20, p 0.005). Seronegative status of the donor (where was known) contributed to 75% (12/16) cases of reactivated toxoplasmosis after allo-HSCT.DiscussionThe presented results show that peripheral blood-based qPCR, both before and after HSCT, is a valuable asset for the diagnosis of reactivated toxoplasmosis, whereas the results of serology in recipients should be interpreted with caution. Weekly qPCR monitoring, at least until successful engraftment and administration of prophylaxis, allows for prompt introduction of specific treatment.     

Toxoplasma gondii infection in the peritoneal macrophages of rats treated with glucocorticoids

It is well known that toxoplasmosis can be life threatening to immunocompromised individuals such as AIDS and organ transplantation patients. Glucocorticoids (GCs) are widely used in the clinic for the treatment of autoimmune diseases and organ transplantation resulting in acute toxoplasmosis in these patients. However, the interaction and mechanism between the development of acute toxoplasmosis and GC therapy are still unknown. The aims of this study were to investigate the infection of Toxoplasma gondii in the peritoneal macrophages of rats treated with glucocorticoids. Our results showed that the growth rate of T. gondii RH strain was significantly increased in the peritoneal macrophages of rats treated with glucocorticoids in vivo. For instance, 242 (±16) tachyzoites were found in 100 macrophages from the rats treated with methylprednisolone (MP), while only 16 (±4) tachyzoites were counted in the macrophages from the non-treated control rats 24 h after infection (P?<?0.01). We also demonstrated that a significant inhibition of nitric oxide (NO) production was detected in the macrophages collected from the rats post-treated with GCs with 12.90 μM (±0.99 μM) of nitrite production from the rats treated with MP, while 30.85 μM (±1.62 μM) was found in the non-treated control rats 36 h after incubation (P?<?0.01). Furthermore, glucocorticoids could significantly inhibit the expression of inducible nitric oxide synthase mRNA and its protein in the rat peritoneal macrophages. Our results strongly indicate that the decrease of NO in the rat peritoneal macrophages is closely linked to the cause of acute toxoplasmosis in the host. Additionally, there was a significant increase in the number of cysts produced by the naturally cyst forming, T. gondii Prugniaud strain with an average of 2,795 (±422) cysts of the parasite being detected in the brains of the rats treated with dexamethasone, while only 1,356 (±490) cysts were found in the non-treated control animals (P?<?0.01). As rats and humans are both naturally resistant to T. gondii infection, these novel data could lead to a better understanding of the development of acute toxoplasmosis during glucocorticoid therapy in humans.     

Coccidioidomycosis in hematopoietic stem cell transplant recipients.

Coccidioidomycosis is an endemic fungal infection of the desert southwestern United States that can cause devastating disseminated infection in immunocompromised persons. Clinical coccidioidomycosis, which is caused by Coccidioides species, has been well characterized in patients who have had solid organ transplants, but it has rarely been described in patients who have received a hematopoietic stem cell transplant (HSCT). We report the experience of 121 consecutive HSCT recipients at a single tertiary care institution in an endemic area. One patient had fatal disseminated coccidioidomycosis after receiving an allogeneic transplant, and 2 patients had pulmonary infection before successful autologous HSCT; 1 of these 2 had a reactivation of coccidioidal infection after HSCT but was treated and survived. Coccidioidomycosis was not commonly identified in HSCT recipients, even in the endemic area. A prospective evaluation is required to address the optimal use of coccidioidal serologic tests, antifungal protocols, and secondary prophylaxis in these patients.     

Fulminant toxoplasmosis in a heart transplant recipient

Toxoplasma gondii infections in heart transplant recipients emerge in most cases as newly acquired infections of the immunocompromised sero-negative patient from an exogenous source, usually the donor organ. We report on a 64-year-old heart transplant recipient who developed pneumonitis, myocarditis, and hyperacute encephalitis three weeks after transplantation. Histopathological examination of an endomyocardial biopsy revealed fulminant T. gondii infection. Although appropriate chemotherapy was administered immediately, the patient died the next day. Our case demonstrates that if a histological diagnosis is not rendered in time, fulminant toxoplasmosis may lead to a fatal outcome. In conclusion, a general screening of the donors and recipients for opportunistic infections, including toxoplasmosis, and an appropriate prophylaxis should always be considered.     

Co-Infections with Cytomegalovirus and Human Herpesvirus Type 7 in Adult Polish Allogeneic Haematopoietic Stem Cell Transplant Recipients

Human herpesvirus 7 (HHV-7) is widespread around the world and may also be a possible cofactor for cytomegalovirus (CMV) infection in haematopoietic stem cell transplant (HSCT) recipients. In case of viral diseases where specific treatment is available, real-time PCR assays constitute reliable diagnostic tools enabling timely initiation of appropriate therapy and rapid assessment of the efficacy of antiviral treatment strategies. The presence of CMV and HHV-7 was confirmed by the detection of viral DNA isolated from 1,027 plasma samples. A group of 69 allogeneic HSCT (alloHSCT) recipients was examined in early post-transplant period using quantitative real-time PCR methods. Within the study period, 62 % of patients had at least once CMV DNA-emia, while HHV-7 DNA was found in 43 % of subjects. Co-infection between these β-herpesviruses was detected in the plasma samples collected from 18 patients (26 %). Patients with concomitant HHV-7 DNA-emia had significantly higher number of CMV DNA copies compared with those without HHV-7 infection (1986 vs. 432 copies/ml, p < 0.001) but there was no difference in duration of CMV DNA-emia between these groups. On the other hand, while the load of HHV-7 DNA was comparable between patients with CMV DNA-emia and without CMV DNA-emia, the duration of HHV-7 DNA-emia was significantly longer in the first group (38.5 vs. 14 days, p < 0.001). HHV-7 DNA-emia is very frequently detected in Polish alloHSCT recipients. In those, who have subsequent CMV reactivation, the coexistence of the viruses may negatively affect the kinetics of infection with either of them. Therefore the investigation of concomitant HHV-7 DNA-emia could affect the prognosis of post-transplant patients suffering from CMV reactivation.     

Bloodstream Infection after Stem Cell Transplantation in Children with Idiopathic Aplastic Anemia

Bloodstream infection (BSI) is the most common infectious complication of hematopoietic stem cell transplantation (HSCT) and can cause substantial morbidity and mortality. Identification of risk factors for BSI might be helpful in efforts to reduce transplantation-related death. This study analyzed the incidence of BSI and risk factors for BSI after HSCT in pediatric patients with aplastic anemia (AA). BSI occurred in 39 of the 351 patients with AA (11.1%). Onset of BSI occurred at a median of 8 days after HSCT (range, 0 to 92 days). The 5-year overall survival rate was lower in patients with BSI than in patients without BSI (63.32% ± 7.90% versus 93.35% ± 1.44%; P < .0001). Univariate analysis identified the following variables as associated with BSI: history of immunosuppressive therapy with antithymocyte globulin (ATG), transplantation from an unrelated donor, frequent blood transfusion before transplantation, major or major plus minor ABO type mismatch, graft-versus-host disease prophylaxis with tacrolimus and without cyclosporine, and long interval from diagnosis to transplantation. Among these factors, long interval from diagnosis to transplantation was the sole statistically significant risk factor for BSI on multivariate analysis. In patients who underwent HSCT from a related donor, age ≥14 years at transplantation was risk factor for BSI. In contrast, history of immunosuppressive therapy with ATG, frequent blood transfusion before HSCT, graft failure, and major or major plus minor ABO type mismatch were risk factors for BSI in patients who underwent HSCT from an unrelated donor. Because the overall 5-year survival rate without BSI was >90%, even in patients who were received a transplant from an unrelated donor, control of BSI is very important for successful HSCT in pediatric patients with AA.     

Nonmalignant Late Effects in Survivors of Partially Matched Donor Hematopoietic Stem Cell Transplantation

Human leukocyte antigen (HLA) partially matched related donor (PMRD) hematopoietic stem cell transplantation (HSCT) is an effective option for hematological malignancies. In this study, the nonmalignant late effects of PMRD HSCT were evaluated and compared with HLA-identical sibling donor (ISD) HSCT. Three hundred thirteen patients (ISD, n = 160; PMRD, n = 153) who survived at least 6 months and received regular follow-up examinations after their HSCT were enrolled. The 5-year cumulative incidence (±SE) of at least one late effect and multiple late effects was 47.30% ± .17% versus 58.21% ± .16% (P = .134) and 17.97% ± .10% versus 34.28% ± .15% (P = .001) for PMRD HSCT recipients versus ISD HSCT recipients, respectively. The cumulative incidence of keratoconjunctivitis sicca, periodontitis, ankylosis, myalgia, and nephrotic syndrome was lower among PMRD HSCT recipients compared with ISD HSCT recipients. Severe chronic graft-versus-host disease, multiple pre-HSCT chemotherapy cycles, female donor, and older age were risk factors for at least one late effect. Female donor, older age, and long-term immunosuppressive therapy were associated with multiple late effects. In summary, PMRD HSCT recipients have a lower risk of late effects compared with ISD HSCT recipients, possibly due to differences in protocols for graft-versus-host disease prophylaxis, and long-term follow-up after transplantation is recommended.     

Pneumocystis jirovecii pneumonia 13 years post renal transplant following a recurrent cytomegalovirus infection

Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP) is a rare but serious infection that usually occurs within a year after solid organ transplantation. PCP may occur after 1?year post transplantation, but the rate is reported to be very low. Studies have shown an association between cytomegalovirus (CMV) infection in solid organ transplant patients and an increased risk of opportunistic infection. This increased risk is thought to be a result of the immunomodulatory effects of the CMV infection. We present a case of PCP infection occurring 13?years after a renal transplantation. This occurred following a recurrent CMV infection while the patient was on low-dose immunosuppressants.     

Characteristics comparisons of bacteremia in allogeneic and autologous hematopoietic stem cell-transplant recipients with levofloxacin prophylaxis and influence on resistant bacteria emergence

Background

The aim of this study was to compare the risk factors and clinical outcomes of bacteremia in allogeneic and autologous hematopoietic stem cell transplant (allo-HSCT and auto-HSCT) recipients with levofloxacin prophylaxis during the early period after transplantation.

Tolerance induction in HLA disparate living donor kidney transplantation by facilitating cell-enriched donor stem cell Infusion: The importance of durable chimerism

Successful solid organ transplantation currently requires the life-long use of medications to suppress the immune system in order to prevent transplant rejection. Drug-based immunosuppression significantly increases the risk of infection and cancer, as well as being very costly. Development of new therapies to minimize or eliminate entirely the need for anti-rejection drugs is of great interest to the transplant community. Therapeutic cell transfer for the control of the human immune system represents a compelling approach to reduce or eliminate the need for anti-rejection drugs. Establishment of durable hematopoietic chimerism through hematopoietic stem cell transplantation (HSCT) has been shown in preclinical models and patients to lead to donor specific tolerance. However, the application HSCT is limited by the potential toxicity of conditioning regimens, the risk of graft versus host disease (GVHD) and the challenge of HLA mismatching. In this review we describe the clinical outcomes and science behind a CD8⁺/TCR^? facilitating cell-based hematopoietic stem cell transplant approach (termed FCRx) to induce tolerance to mismatched renal allografts while minimizing the risk of graft-versus-host GVHD and achieving avoidance of long-term immunosuppressant drugs in living donor kidney transplant recipients.     

Monoclonal antibody HBME-1 reacts with a minor subset of B cells with villous surface and can be useful in the diagnosis of hairy cell leukemia and other indolent lymphoproliferations of villous B lymphocytes

The Hector Battifora mesothelial epitope-1 (HBME-1) monoclonal antibody has been generated against human mesothelioma cells and recognizes a biochemically unknown membrane epitope. We have accidentally found that the HBME-1 reacts with scattered lymphocytes showing villous surface in hyperplastic lymphoid tissue. To evaluate its reactivity pattern, we have performed a consecutive immunohistochemical study in nonneoplastic bone marrow and lymphoid samples (n?=?40), as well as in malignant lymphoproliferations (n?=?427), including hairy cell leukemia (HCL) (n?=?72), HCL variant (HCL-v) (n?=?13), splenic diffuse red pulp small B cell lymphoma (SDRPL) (n?=?8), splenic B cell marginal zone lymphoma (SMZL) (n?=?59), and splenic B cell lymphoma/leukemia, not further classifiable on bone marrow morphology (SBCL) (n?=?37) cases. The staining pattern of HBME-1 was compared to DBA.44. HBME-1⁺ villous lymphocytes were constantly detected in low number in nonneoplastic lymphoid tissues. With multicolor immunofluorescence staining, HBME-1⁺ lymphocytes showed a CD20⁺/CD79a⁺/IgM⁺ B cell phenotype. In B cell lymphoproliferations of villous lymphocytes, HBME-1 reactivity was demonstrated in 96 % of HCL, 39 % of HCL-v, 50 % of SDRPL, 12 % of SMZL, and 19 % of SBCL cases. Nodal and extranodal marginal zone lymphoma cases were positive in 12 % of the cases. A small minority (4 %) of the other B cell lymphomas and no T cell lymphoma revealed tumor cell reactivity with HBME-1. In conclusion, our study has established that HBME-1 reacts with a minor subset of B lymphocytes and a small proportion of B cell lymphomas, which has not been described previously. We suggest that HBME-1 can be a useful marker in the diagnosis of HCL and other indolent lymphoproliferations of villous B lymphocytes.     

Toxoplasmosis as an Early Complication of Allogeneic Hematopoietic Cell Transplantation

Among 419 consecutive allogeneic hematopoietic cell transplant recipients, we observed 17 (4.0%) cases of toxoplasmosis at a median time of day 45 (range, 6 to 322) after transplant. Seven of these 17 cases occurred before day 30 after transplant. Because of the lack of PCR screening and trimethoprim-sulfamethoxazole prophylaxis before engraftment, the diagnosis of toxoplasmosis was late, and 5 of these 7 patients died. Analyzing these cases, early Toxoplasma blood PCR screening, starting from transplant, is crucial.