Psychosocial predictors of distress in parents of children undergoing stem cell or bone marrow transplantation

OBJECTIVE: To examine psychosocial predictors of distress (mood disturbance, perceived stress, caregiver burden) in parents of children undergoing stem cell or bone marrow transplantation (BMT). METHOD: Measures of prior illness experiences, premorbid child behavior problems, family environment, social support, and parental coping behavior were obtained from the resident parents of 151 children prior to the children's admission for BMT. Parents subsequently completed assessments of their mood disturbance, perceived stress, and caregiving burden on a weekly basis through week +6 post-BMT, and then monthly through month +6 post-BMT. RESULTS: Significant changes were observed in parental distress across the course of BMT. After correcting for demographic and medical factors, several significant predictors of parental distress trajectories were identified, including prior parent and patient illness-related distress, premorbid child internalizing behavior problems, the family relationship dimensions of the family environment, and parental avoidant coping behaviors. Multivariable models were developed using a hierarchical modeling approach. The best-fit model accounted for approximately 50% of the variance in parental global distress. CONCLUSIONS: Subgroups of parents at higher risk for increased distress during the acute phase of transplant have been identified. These findings can help target parents who may be in greater need of intervention aimed at reducing transplant-related distress.     

伏立康唑与两性霉素B脂质体治疗艾滋病合并播散性马尔尼菲青霉菌病的对照研究

目的比较伏立康唑和两性霉素B脂质体治疗艾滋病（AIDS）合并播散性马尔尼菲青霉菌病（PSM）的疗效及安全性。方法对经血/骨髓培养确诊为AIDS合并PSM的患者,分别给予伏立康唑和两性霉素B脂质体治疗,疗程28d,比较两组的疗效和安全性。结果共52例患者纳入研究,其中伏立康唑治疗组20例,两性霉素B脂质体治疗组32例。治疗14d和28d时,伏立康唑组和两性霉素B脂质体组的治疗有效率分别为40.0%、65.0%和56.3%、71.9%,两组比较差异均无统计学意义（Z=1.300,P=0.254;Z=0.273,P=0.601）,但两组28d的治疗有效率均明显高于14d（Z=3.994,P=0.046）。治疗过程中,两组均未出现因毒副作用停药的现象,但两性霉素B脂质体组临床毒副反应较重且出现了血清肌酐的升高。结论伏立康唑与两性霉素B脂质体均为治疗AIDS合并PSM的有效方法,但伏立康唑安全性更好。     

Histopathological changes in bone marrow biopsies from patients with chronic myeloid leukaemia after treatment with recombinant alpha-interferon

Aims : Recombinant alpha-interferon (r-IFN) is an effective therapy for chronic myeloid leukaemia (CML), inducing haematological and major cytogenetic response in 70% and 30% of patients, respectively. In this study we have evaluated the significance of bone marrow (BM) histology on the subsequent response to r-IFN therapy, as well as the morphological changes induced by r-IFN within BM. Methods and results : 73 BM biopsies were studied from 21 patients with Ph¹-positive CML in chronic phase at diagnosis and at different times during r-IFN treatment. At diagnosis the probability of achieving a major or complete cytogenetic response was significantly higher in patients with a total marrow cellularity lower than 90% ( P  = 0.02). During therapy with r-IFN, significant BM changes included disappearance of the CML pattern ( P  = 0.0002), reduction of M:E ratio ( P  = 0.0009) and total cellularity ( P  = 0.0027), and increase in number of terminal megakaryocytes ( P  = 0.0009) and of fatty tissue regeneration ( P  = 0.037); only after long-term therapy (mean 20 months), did reticulin fibrosis increase significantly ( P  = 0.032). Conclusions : The overall BM morphology in response to treatment displayed different pictures, ranging from persistence of CML (25 biopsies out of 51), to reversion to normal histology (14 out of 51). Persistence of diffuse morphological abnormalities was associated with lack of cytogenetic responsiveness ( P  = 0.025).     

Prophylactic administration of voriconazole with two different doses for invasive fungal infection in children and adolescents with acute myeloid leukemia

Background

Pediatric patients under treatment for acute myeloid leukemia (AML) are at high risk for invasive fungal infection (IFI). We evaluated the efficacy of prophylactic administration of voriconazole (VRCZ) with two different doses.

Cytomegalovirus antibody avidity in allogeneic bone marrow recipients: Evidence for primary or secondary humoral responses depending on donor immune status

The reconstitution of the human cytomegalovirus (CMV) antibody response in CMV seropositive bone marrow transplant patients was investigated by comparing 11 patients whose donors were CMV seropositive with 8 whose donors were CMV seronegative. Evidence for primary or secondary responses to CMV was sought by determining IgG antibody avidity using an avidity index method, and antibody titre over a period of up to 3 years after transplant. For the patients whose donors were CMV seropositive, the results showed the characteristics of a secondary response, i.e., rising antibody titres of high avidity immediately after transplant. In contrast, the patients with CMV seronegative donors showed evidence of a primary antibody response usually occurring at about 250 days after transplant, i.e., rising antibody levels initially of low avidity maturing to high avidity over the following 100 to 200 days. It is concluded that a secondary response and hence transfer of humoral immunity had occurred in those patients whose donor was CMV seropositive, whereas a delayed primary response occurred in those patients whose donor was CMV seronegative. © 1996 Wiley-Liss, Inc.     

Efficacy of voriconazole plus amphotericin B or micafungin in a guinea-pig model of invasive pulmonary aspergillosis

The efficacy of voriconazole in combination with amphotericin B or micafungin was studied in a transiently neutropenic guinea-pig model of invasive pulmonary aspergillosis. Guinea-pigs treated with the antifungal drugs, alone or in two-drug combinations, had an improved survival rate and reduced fungal burden in the lungs compared to untreated control animals. The efficacy of monotherapy and combination therapy was similar; activity was neither enhanced nor reduced with the two-drug combinations. Further studies of efficacy, dosing and optimal regimens for antifungal combinations are warranted.     

Brief report: parents of children undergoing bone marrow transplantation: documenting stress and piloting a psychological intervention program

OBJECTIVE: To document levels of stress in parents of children undergoing bone marrow transplantation (BMT) over the course of hospitalization and to pilot a psychological intervention program designed to teach parents techniques for managing stress associated with their child's illness and hospitalization. METHODS: Twenty-two mothers of children (ages 2-16) undergoing BMT were followed prospectively from preadmission to three weeks posttransplant. Eleven mothers, randomly assigned to participate in a pilot intervention program, were compared with 11 control mothers receiving standard care preparation of their child's BMT. RESULTS: Repeated measures ANOVAs detected significant changes in stress over time, with most stress reported preadmission. Mothers in the intervention condition reported using more stress management techniques than mothers in the standard care condition, though the majority of analyses revealed no significant differences in stress between groups. CONCLUSIONS: Increased levels of parenting distress may occur pretransplant, suggesting the need for additional psychological intervention at that time.     

Dominance and persistence of donor marrow in long-lived allogeneic radiation chimeras obtained with unmanipulated bone marrow

Allogeneic, H-2-incompatible irradiation chimeras (H-2d leads to H-2b) constructed with normal, unmanipulated bone marrow and with marrow-derived factors live long and do not manifest a GvH disease. Their response to primary immunization is deficient but their alloreactivity is normal. This chimeric allotolerance cannot be passively transferred from chimeric donors to normal irradiated recipients. Passive transfer of both donor- or recipient-type immunocompetent T-cells into the chimeric mice does not lead to syngeneic reconstitution, rejection of the engrafted marrow or GvH disease and the mice maintain permanently their chimerism. This new model demonstrates that chimerism is not eradicable in long-lived chimeras reconstituted with unmanipulated bone marrow, and that the bone marrow itself plays a dominant role in maintenance of chimerism.     

Direct detection of the human papovavirus BK in urine of bone marrow transplant recipients: comparison of DNA hybridization with ELISA

Urine specimens from bone marrow transplant (BMT) recipients and from controls were directly tested for BK virus (BKV) DNA sequences by dot hybridization and for BKV antigen by a double-antibody indirect ELISA. A total of 158 specimens from 55 BMT patients (57 collected prior to or at the time of transplantation and 101 in the posttransplant period) and single urines from 125 control subjects were examined by both methods. A molecularly cloned, 32P-labelled BKV probe was hybridized with urine sediments that were spotted directly on nitrocellulose filters and denatured in situ. BKV DNA sequences were detected in 1 (1.8%) pretransplant and 22 (21.8%) posttransplant urines of BMT patients, and in none of control urines. In ELISA of urine supernatants, BKV antigen was detected in 1 (1.8%) pretransplant and 21 (20.8%) posttransplant urines of BMT patients and in 1 (0.8%) of the control urines. The results of the two tests correlated as follows: 16 urines were positive and 253 urines negative by both methods; seven specimens were positive by DNA hybridization only and seven were positive by ELISA alone. Virus excretion in urine was demonstrated in 20 (36.4%) patients by DNA hybridization, in 19 (34.5%) patients by ELISA, in 15 (27.3%) patients by both methods, and in 24 (44%) patients by at least one of the two tests.     

T cell lymphoblastic leukaemia/lymphoma associated with a microenvironment of thymic asteroid B cells in the bone marrow

Naresh K N, May P C, Reid A G, Marks A J, Macdonald D & Kanfer E
(2010) Histopathology 57, 549–554
T cell lymphoblastic leukaemia/lymphoma associated with a microenvironment of thymic asteroid B cells in the bone marrow Aims: Asteroid B cells are a component of normal thymus. It is currently unclear whether these cells are identifiable in T cell lymphoblastic leukaemia/lymphoma (T‐ALL/LBL) of the thymus. The aim of this study was to identify asteroid B cells both in thymic and extrathymic tissue involved by T‐ALL/LBL. Methods and results: Thymic, lymph node (LN) and bone marrow trephine biopsy (BMTB) samples from eight patients with T‐ALL/LBL were reviewed. All had been investigated by immunohistochemistry and one by fluorescent in situ hybridization (FISH). The BMTB samples of two of eight T‐ALL/LBLs and LN sample in one of them showed the presence of asteroid‐shaped B cells with dendritic cytoplasmic processes. These B cells also expressed CD23 and the features were akin to the unique thymic asteroid B cells. Both patients had aggressive/resistant disease. Cytogenetic analysis in one showed a complex translocation involving the T cell receptor beta (TCRB) gene at 7q35 and a distal region of 9q known to harbour the NOTCH1 gene. Conclusion: This is the first report of T‐ALL/LBL documenting the presence of an asteroid B cell‐rich microenvironment at bone marrow and LN sites. In this small subset, T‐ALL/LBL cells are possibly dependent upon asteroid B cells, and whether targeting of asteroid B cells with anti‐CD20 monoclonal antibody in such cases will result in clinical benefit remains to be determined.     

Effects of ethanol consumption and withdrawal on B cell subpopulations in murine bone marrow.

We designed studies to examine the effects of ethanol consumption and withdrawal on the numbers of pre-B and B cells in murine bone marrow. Flow cytometric analysis of B220 and surface IgM expression on bone marrow cells revealed that consumption of ethanol by mice for 7 days led to a significant reduction in pre-B cells. The number of mature B cells in the bone marrow of these animals, however, did not differ from that of control mice. In contrast, examination of bone marrow obtained from mice at various times after withdrawal from ethanol showed significantly fewer numbers of mature B cells and an even greater loss of pre-B cells. This effect was seen for relatively long periods after withdrawal. These study findings are interpreted to suggest that ethanol consumption results in changes in the pre-B cell population in murine bone marrow. It also appears that withdrawal from ethanol results in more profound changes in the mature B cell population of the bone marrow than those that occur during ethanol consumption.     

Large B cell lymphoma presenting initially in bone marrow, liver and spleen: an aggressive entity associated frequently with haemophagocytic syndrome

Yeh Y‐M, Chang K‐C, Chen Y‐P, Kao L‐Y, Tsai H‐P, Ho C‐L, Wang J‐R, Jones D & Chen T‐Y
(2010) Histopathology 57, 785–795 Large B cell lymphoma presenting initially in bone marrow, liver and spleen: an aggressive entity associated frequently with haemophagocytic syndrome Aims: To describe diffuse large B cell lymphoma (DLBCL) presenting initially in bone marrow, liver and spleen (BLS‐type) without lymphadenopathy. Methods and results: The clinicopathological and cytogenetic features of 11 such cases (eight men, three women; mean age: 62.7 years are described). Usually presenting with fever and haemophagocytic syndrome suggesting infection and complicating timely diagnosis, bone marrow examination showed patchy and interstitial infiltration of large tumour cells without sinusoidal involvement. All cases had a high Ki‐67 index (≥90%), commonly a non‐germinal centre/activated B cell immunophenotype and were negative for Epstein–Barr virus and human herpesvirus 6 and 8. The more frequent cytogenetic changes involved chromosomal loci 14q32 and 9p24, as well as del(3)(q21), add(7)(p22), t(3;6), del(8)(p22), +18 and add(19)(p13). Clinical behaviour was very aggressive, with a 2‐year survival rate of 18% (45% of patients died within 3 weeks). High‐dose chemotherapy with haematopoietic stem cell transplantation prolonged survival in one patient. Conclusions: Although it shares with intravascular LBCL a subtle presentation and an aggressive clinical course, this primary BLS large cell lymphoma variant is distinguished by lacking an intravascular component and having different cytogenetic findings.     

Assessment of ica operon carriage and biofilm production in Staphylococcus epidermidis isolates causing bacteraemia in bone marrow transplant recipients

The clinical significance of coagulase-negative staphylococci isolated from blood culture is typically assessed on the basis of a combination of clinical and microbiological criteria. However, these criteria are difficult to apply to haematology patients who are highly immunosuppressed and from whom blood cultures are obtained most frequently through a central venous catheter. This study analysed 112 episodes of Staphylococcus epidermidis bacteraemia that occurred in 79 bone marrow transplant recipients. In 73 (65%) episodes, only one blood culture set was positive for S. epidermidis, while 39 (35%) episodes grew S. epidermidis from multiple blood cultures. Nine patients had two or more episodes of bacteraemia with the same strain, as determined by pulsed-field gel electrophoresis (PFGE). The PFGE method also showed that 34 (31%) isolates belonged to seven clusters, indicating the persistence of certain clones in the environment. Of the 109 isolates analysed, 59 (54%) produced biofilm and 91 (83.5%) carried the ica operon. Isolates that produced biofilm were observed to colonise central venous catheters faster than non-biofilm-producing isolates (18 vs. 37 days; p 0.03). No clinical features were associated with carriage of the ica operon, but the ica operon was carried more frequently by the isolates that formed clusters.     

Anti-herpesvirus prophylaxis,pre-emptive treatment or no treatment in adults undergoing allogeneic transplant for haematological disease: systematic review and meta-analysis

BackgroundHerpesviridae infections incur significant morbidity and indirect effects on mortality among allogeneic haematopoietic cell transplant (allo-HCT) recipients.ObjectivesTo study the effects of antiviral prevention strategies among haemato-oncological individuals undergoing allo-HCT.Data sourcesCochrane Central Register of Controlled Trials, MEDLINE, Embase and LILACS. We further searched for conference proceedings and trial registries.Study eligibility criteriaRandomized controlled trials (RCTs).ParticipantsAdults with haematological malignancy undergoing allo-HCT.InterventionsAntiviral prophylaxis versus no treatment/placebo or pre-emptive treatment and pre-emptive treatment versus prophylaxis with the same agent.MethodsRandom-effects meta-analysis was conducted computing pooled risk ratios (RR) with 95% CI and the inconsistency measure (I²). The certainty of the evidence was appraised by GRADE.ResultsWe included 22 RCTs. Antiviral prophylaxis reduced all-cause mortality (RR 0.83, 95% CI 0.7–0.99; 15 trials, I² = 0%), cytomegalovirus (CMV) disease (RR 0.54, 95% CI 0.34–0.85; n = 15, I² = 20%) and herpes simplex virus (HSV) disease (RR 0.29, 95% CI 0.2–0.43; n = 13, I² = 18%) compared with no treatment/placebo or pre-emptive treatment, all with high-certainty evidence. Furthermore, antivirals reduced HSV infection, CMV pneumonitis, CMV infection and varicella zoster virus disease. Anti-CMV prophylaxis (+/– pre-emptive treatment) compared with pre-emptive treatment alone reduced non-significantly all-cause mortality (RR 0.78, 95% CI 0.6–1.02; n = 8, I² = 0%), CMV disease (RR 0.47, 95% CI 0.23–0.97; n = 9, I² = 30%) and HSV disease (RR 0.41, 95% CI 0.24–0.67; n = 4, I² = 0%) with high-certainty evidence, as well as CMV and HSV infections. Antiviral prophylaxis did not result in increased adverse event rates overall or more discontinuation due to adverse events.ConclusionsAntiviral prophylaxis directed against herpesviruses is highly effective and safe, reducing mortality, HSV and CMV disease, as well as herpesvirus reactivations among allo-HCT recipients. Anti-CMV prophylaxis is more effective than pre-emptive treatment alone with respect to HSV and CMV disease and infection.     

The identification and characteristics of IL-22-producing T cells in acute graft-versus-host disease following allogeneic bone marrow transplantation

Graft-versus-host disease (GVHD) remains the major obstacle for allogeneic bone marrow transplantation, in which many proinflammatory cytokines secreted by alloreactive donor T cells are involved. Role of IL-22 as a member of IL-10 family in GVHD is still disputed and the properties of IL-22-producing cells are unclear. We demonstrated here that CD4⁺ T cells but not CD8⁺ T cells involved in GVHD were the main cellular source of donor-derived IL-22. Th1 and Th17 cells were detected not only express classical cytokine IFN-γ or IL-17, but also contributed to IL-22 secretion in GVHD. Th22 cells characterized by the independent secretion of IL-22 were identified and occupied almost half percentage of IL-22-producing CD4⁺ T cells. The frequency of IL-22-producing CD4⁺ T cells showed dynamic changes with the development of GVHD. Finally, we observed that IL-22-producing CD4⁺ T cells in GVHD mouse carried CD62L⁻CD44^high/low surface markers. In conclusion, we illuminate the characteristics of donor-derived IL-22-producing CD4⁺ T cells, which may have potent implication for further study of pathogenesis of GVHD.     

Changes in the hepatitis B surface antibody in childhood acute lymphocytic leukaemia survivors after treatment with the CCLG‐ALL 2008 protocol

Antibody levels after hepatitis B virus (HBV) vaccination may be affected by suppression of the immune system due to cancer therapy. As such, childhood acute lymphocytic leukaemia (ALL) survivors are at risk of HBV infection due to immunosuppression secondary to chemotherapy. However, the hepatitis B surface antibody (HBsAb)‐seropositive rate of childhood ALL survivors after chemotherapy is unknown, and the need to revaccinate HBsAb‐seronegative ALL survivors is not appreciated in China. To assess the changes in HBsAb before and after chemotherapy, we retrospectively analyzed clinical data from 547 patients treated with the Chinese Children Leukaemia Group (CCLG)‐ALL 2008 protocol from 1 April 2008 to 30 August 2019. The results revealed that 416 patients (76·1%) were HBsAb‐seropositive at diagnosis, and at the time of the cessation of chemotherapy, 177 patients (32·4%) were HBsAb‐seropositive and 370 patients (67·6%) were HBsAb‐seronegative. Interestingly, 11 patients who were HBsAb‐seronegative at diagnosis converted to seropositive at the time of the cessation of chemotherapy. HBsAb titres were decreased after chemotherapy (P < 0·0001). Further, patients with higher HBsAb titres at diagnosis were more likely to maintain protective antibody titres at the completion of chemotherapy (P < 0·0001). The loss of antibody was more remarkable in younger patients (≤ 10 years) both at diagnosis (P = 0·009) and at the completion of chemotherapy (P = 0·006). In summary, this study showed that 67·6% of patients were HBsAb‐seronegative at the time of the cessation of chemotherapy, which indicates that ALL survivors are at high risk of HBV. As a result, HBV revaccination after chemotherapy should be highly valued in ALL survivors.     

Predictors of PTSD in mothers of children undergoing bone marrow transplantation: the role of cognitive and social processes

OBJECTIVE: To investigate the role of cognitive and social processing in posttraumatic stress symptoms and disorder (PTSD) among mothers of children undergoing bone marrow and hematopoietic stem-cell transplantation (BMT/SCT). METHOD: Questionnaires assessing emotional distress, BMT-related fears, and negative responses of family and friends were completed by 90 mothers at the time of the BMT infusion and 3 and 6 months post-BMT. PTSD symptoms were measured 6 months post-BMT by both paper-and-pencil and structured interview methods. RESULTS: Emotional distress, BMT-related fears, and negative responses of family and friends assessed at the time of BMT hospitalization were predictive of later PTSD symptoms. None of these variables prospectively predicted a PTSD diagnosis as measured by the structured interview. CONCLUSIONS: Higher levels of general psychological distress, cognitive interpretations of the threat of the BMT for the child's future functioning, and negative responses of family and friends may place mothers at risk for post-BMT posttraumatic stress symptomatology.