Association of pulmonary nontuberculous mycobacteria with the outcomes of patients with lung cancer: A retrospective matched cohort study with a special emphasis on the impact of chemotherapy

IntroductionNontuberculous mycobacteria (NTM) may be present in the respiratory tract of patients with lung cancer. We investigated the association of pulmonary NTM with the clinical features and outcomes of patients with lung cancer.MethodsBetween 2015 and 2019, the data of patients diagnosed with lung cancer at a medical center in northern Taiwan were analyzed. Patients whose respiratory specimens were culture-positive for NTM were identified (NTM group). For each patient in the NTM group, a matched control was selected (control group). The survival of the two groups was compared using the Kaplan–Meier method and Cox proportional hazards regression analysis.ResultsAmong 8718 patients with lung cancer, 5418 (62.1%) underwent a sputum mycobacterial culture. At least one NTM species was isolated from 138 (2.5%) patients. The median age was 72 years (range: 64–80). In the NTM group, 19.8% fulfilled both the microbiological and radiographic criteria for the diagnosis of NTM lung disease. Compared with the control group, the NTM group exhibited a lower body mass index (22.4 vs. 23.6, p = 0.025) and a higher prevalence of structural lung disease (38.9% vs. 22.2%, p = 0.004). The two-year survival was not significantly different between the two groups (hazard ratio [HR]: 1.110; 95% confidence interval [CI]: 0.702–1.754, p = 0.656). In patients receiving chemotherapy, pulmonary NTM was associated with worse survival (HR: 2.497, 95% CI: 1.262–4.943, p = 0.009).ConclusionsExcept in patients receiving chemotherapy, pulmonary NTM may not be clinically relevant in patients with lung cancer.     

Genital Chronic Graft-versus-Host Disease in Females: A Cross-Sectional Study

Using the National Institutes of Health (NIH) consensus criteria for chronic graft-versus-host disease (cGVHD), we assessed the prevalence, symptoms, and clinical signs of female genital cGVHD in a cross-sectional population-based study. Forty-two women were evaluated at a median of 80 months (range, 13 to 148 months) after undergoing hematopoietic stem cell transplantation (HSCT). Medical history, ongoing medications, and genital signs and symptoms were recorded. Gynecologic examination for the diagnosis and clinical scoring of genital cGVHD was combined with clinical scoring of extragenital cGVHD for the estimation of each patient's global cGVHD score. Biopsy specimens from the genital mucosa were obtained from 38 patients. Genital cGVHD was diagnosed in 22 of 42 patients (52%). Its presence was associated with systemic corticoid steroid treatment of extragenital cGVHD (P = .001), older age (P = .07), and HSCT from a sibling donor (P = .002). Five patients had isolated genital cGVHD. Dryness, pain, smarting pain (P < .05 for all), and dyspareunia (P = .001) were observed more frequently in the women with genital cGVHD. Twelve patients had advanced genital cGVHD (clinical score 3), which was the main factor explaining the high rate (15 of 42) of severe global cGVHD. The rate of genital cGVHD was similar (P = .37) in patients with a follow-up of ≥80 months (10 of 22) and those with a follow-up of <80 months (12 of 20). We found no convincing relationship between clinical diagnosis and histopathological assessment of mucosal biopsy specimens. In our group of women with a long follow-up after HSCT, genital cGVHD was common and in many cases incorrectly diagnosed. Genital cGVHD causes genital symptoms and affects sexual life, and may present without any other cGVHD, warranting early and continuous gynecologic surveillance in all women after HSCT.     

Infections after Allogenic Transplant with Post-Transplant Cyclophosphamide: Impact of Donor HLA Matching

Incidence and outcome of infections after allogeneic hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PT-Cy) as graft-versus-host disease (GVHD) prophylaxis are largely unknown. Study aims were to estimate the incidence of pre-engraftment bloodstream infections (PE-BSIs) and viral infections (VIs; cytomegalovirus [CMV], adenovirus [ADV], human herpes virus 6 [HHV6], and BK-polyomavirus hemorrhagic-cystitis [BKPyV-HC]), their predictive factors, and infection-related mortality (IRM) after HSCT with PT-Cy. We analyzed 235 patients: 62%, 21%, and 17% received haploidentical (haplo), matched-unrelated donor (MUD), and matched-related donor, respectively. Overall, 72 patients had 77 PE-BSI episodes at a median time of 13 days after HSCT: cumulative incidence function (CIF) at 28 days was 32%, without differences among donor types (P = .988). By multivariate analysis, CIF of PE-BSI was higher in patients with severe neutropenia before HSCT (adjusted hazard ratio [AHR] = 2.90) and in multidrug-resistant Gram-negative bacteria rectal carriers (AHR = 2.68). IRM at 30 days was 5%, without differences by donor type (P = .106). Overall, 208 patients experienced ≥1 VIs (first occurrence among CMV, HHV6, ADV, BKPyV-HC) at a median time of 20 days after HSCT: CIF at 90 days was 91%, significantly higher in MUD and haplo (P = .0089). By multivariate analysis, also acute GVHD grade ≥2 (AHR = 1.32) and host/donor CMV-serology mismatch (positive/positive versus negative/negative: AHR = 2.95, positive/negative versus negative/negative: AHR = 2.41, negative/positive versus negative/negative: AHR = 2.35) affected VIs occurrence. IRM at 180 days was 8%, without differences among donor types (P = .106). In conclusion, study results did not show a significant impact of donor type on PE-BSI incidence; conversely, MUD and haploidentical transplants retained a higher occurrence of VIs in the early phase after HSCT.     

Clinical and demographic study of non-tuberculous mycobacterial ocular infections in South India

PurposeTo describe demographics, risk factors, antibiotic susceptibility, management and outcomes of ocular infections caused by non-tuberculous mycobacteria (NTM).MethodsA retrospective review of medical case records and microbiology records of patients with ocular infections that were culture positive for non-tuberculous Mycobacteria from January 2014 to December 2018 was done. Antibiotic susceptibility profile was done based on the CLSI guidelines. Laboratory diagnosis for the NTM Species was done by conventional microbiological methods. The species identification was done for stored isolated utilizing polymerase chain reaction targeting 16S rDNA and rpoB gene, followed by DNA sequencing and phylogenetic analysis.ResultsTwenty patients with NTM ocular infections were identified during the study period. A majority of cases presented as 12 infectious keratitis (60%) and three suture-related corneal infiltrates (15%). Common risk factors were history of trauma in 9 (45%) patients and history of ocular surgery in 5 (25%) patients. Patients were treated with combination of amikacin and flouroquinolones/chloramphenicol (70%) and surgical interventions were performed in 25% cases. Only twelve isolates were stored and ten isolates were identified as the M. abscessus subsp. abscessus and two isolates as M. abscessus subsp. massiliense by sequencing and phylogenetic analysis. Majority of the NTM were sensitive to amikacin (75%) followed by moxifloxacin, ciprofloxacin, cephotaxime and tobramycin (35%).ConclusionHigh degree of clinical suspicion, multidrug antibiotic therapy and timely surgical intervention in patients with NTM infections, are advised for better clinical outcomes. Prior ocular trauma, prior ocular surgery and presence of biomaterials were the major predisposing factors. Earlier surgical intervention in cases where abscesses or biomaterials are involved, is necessary for rapid recovery.     

Nontuberculous mycobacterial infection after lung transplantation: A single-center experience in South Korea

PurposeNontuberculous mycobacteria (NTM) infection is an important issue after lung transplantation. However, a large-scale epidemiological study on this issue in Korea is lacking. We aimed to evaluate the epidemiology of NTM infection after lung transplant surgery in Korea.MethodsBetween October 2012 and December 2018, we retrospectively evaluated lung transplant recipients in a referral hospital in South Korea. A total of 215 recipients were enrolled. The median age at transplantation was 56 years (range, 17–75), and 62% were men. Bronchoscopy was performed according to the surveillance protocol and clinical indications. A diagnosis of NTM infection was defined as a positive NTM culture from a bronchial washing, bronchoalveolar lavage sample, or two separate sputum samples. We determined NTM pulmonary disease (NTM-PD) according to the American Thoracic Society/Infectious Disease Society of America 2007 guidelines. The Kaplan–Meier method and log-rank test were used for conditional survival analysis in patients with follow-up of ≥12 months.ResultsFourteen patients (6.5%) were diagnosed with NTM infection at a median of 11.8 months (range, 0.3–51.4) after transplantation. Nine patients (4.2%) were diagnosed with NTM-PD, and the incidence rate was 1980/100,000 person-years. Mycobacterium abscessus was the most common species causing NTM-PD (66%), followed by M. avium complex (33%). The presence of NTM infection did not influence all-cause mortality among those who underwent follow-up for ≥12 months (N = 133, log-rank P = 0.816).ConclusionThe incidence of NTM-PD was considerably high among lung-transplant recipients. M. abscessus was the most common causative species of NTM-PD after lung transplantation.     

Differences in Graft-versus-Host Disease Characteristics between Haploidentical Transplantation Using Post-Transplantation Cyclophosphamide and Matched Unrelated Donor Transplantation Using Calcineurin Inhibitors

We assessed differences in presentation and response to therapy in 394 consecutive patients who developed acute or chronic graft-versus-host disease (GVHD) after receiving their first allogeneic transplantation (HSCT) from a 10/10 HLA allele-matched unrelated donor (MUD; n = 179) using calcineurin inhibitors or a T cell-replete haploidentical donor (haplo; n = 215) and post-transplantation cyclophosphamide at our center between 2005 and 2017. The median duration of follow-up for survivors was 52.5 months. The cumulative incidences for grade II-IV and grade III-IV acute GVHD at day 180 post HCT were similar, at 39% and 14%, respectively, for haplo-HSCT compared with 50% and 16% for MUD HSCT (P not significant). Haplo-HSCT recipients had a lower cumulative incidence of moderate to severe chronic GVHD, at 22% (severe, 19%), compared with 31% (severe, 29%) for MUD HSCT recipients (P = .026). The time to onset of moderate to severe chronic GVHD was faster for haplo-HSCT recipients (213 days versus 280 days; P = .011). Among patients with grade II-IV acute GVHD, there was no significant between-group difference in organ involvement, with skin the most affected (75% for haplo-HSCT versus 70% for MUD HSCT), followed by the gastrointestinal tract (71% versus 69%) and liver (14% versus 17% MUD). For chronic GVHD, haplo-HSCT recipients had less involvement of the eyes (46% versus 75% for MUD; P < .001) and of the joints/fascia (12% versus 36%; P = .001). Also for cGVHD patients, haplo-HSCT recipients and MUD HSCT recipients had similar all-cause mortality (22% versus 18%; P = .89), but the former were more likely to be off immunosuppression at 2 years post-HCT (63% versus 43%; P = .03) compared with MUD.     

A low incidence of nontuberculous mycobacterial infections in pediatric hematopoietic stem cell transplantation recipients.

Hematopoietic stem cell transplantation (HSCT) is being used to treat a wide spectrum of clinical disorders but opportunistic infection remains an important factor determining outcomes for these patients. Nontuberculous mycobacterial (NTM) infections are being reported more frequently in HSCT recipients and the incidence of NTM infections in adult recipients is reported to be 0.4%-4.9%. However, the incidence and severity of NTM infections are less well described in pediatric HSCT recipients. Centers for Disease Control and Prevention guidelines were used to define definite and probable NTM infection among 132 children undergoing 169 HSCT between January 2000 and December 2004 at our institution. NTM infection was diagnosed in 5 of 132 pediatric recipients (3.8%). There were no NTM infections diagnosed in the autologous HSCT recipients and the incidence of NTM in allogeneic HSCT recipients was 6.4% (95% confidence interval, 0.8-11.9). The mean age of the HSCT recipients who developed NTM infections was 8 years (range, 2-19 years); 3 were male and 2 were female. Four conditioning regimens included alemtuzumab and 3 had antithymocyte globulin. Of the 5 patients with NTM infections, 2 met the criteria for definite infection and 3 for probable infection. Of the 2 patients with definite NTM infection, 1 had disseminated disease with Mycobacterium avium complex and the other had Mycobacterium chelonae catheter-related bloodstream infection. The probable NTM infections were 1 skin infection with Mycobacterium kansasii and 2 lower respiratory tract infections with M avium complex. Median time to NTM infection was 115 days (range, 14-269 days) after HSCT. Two patients had graft-versus-host disease at the time of NTM infection. All 5 patients received 3-4 antimycobacterial drugs and all NTM infections resolved. In summary, the incidence of NTM infection in pediatric HSCT recipients appears similar to that described in adult HSCT recipients and the outcome appears to be excellent with the proper antibiotic therapy. The increased use of anti-T cell antibodies appears to be associated with an increased risk of NTM infections in pediatric HSCT recipients. Multicenter studies are needed to identify the risk factors, early diagnostic criteria, and optimal therapy.     

Mismatch on Glutathione S-Transferase T1 Increases the Risk of Graft-versus-Host Disease and Mortality after Allogeneic Stem Cell Transplantation

Several drug-metabolizing enzymes, preferentially expressed in the liver, have the potential to act as minor histocompatibility antigens. In the present study, we analyzed the impact of glutathione S-transferase T1 (GSTT1), glutathione S-transferase M1, glutathione S-transferase P1, and UDP glucuronosyl transferase 2B17 (UGT2B17) disparities on the outcome of 125 patients undergoing allogeneic hematopoietic stem cell transplantation. Grades 2 to 4 acute graft-versus-host disease (aGVHD) developed in 56.2% versus 73.3% of GSTT1-matched versus mismatched patients (P = .048). Remarkably, 8.6% GSTT1-matched patients developed grades 2 to 4 liver aGVHD, compared with 36.8% among GSTT1-mismatched recipients (P < .001). Regarding chronic graft-versus-host disease (cGVHD), 34.8% versus 70.7% matched versus mismatched patients developed overall cGVHD (P = .038) and 16.3% versus 48% developed hepatic cGVHD (P = .006). We also found a strong association between the UGT2B17 mismatch and the risk of severe aGVHD (P = .001), especially with gut involvement (P < .001). Most striking was the influence of the GSTT1 mismatch on nonrelapse mortality (26.8% versus 52.6%, P = .031) and overall survival (62% versus 36.9%, P = .045). In summary, UGT2B17 and GSTT1 mismatch are risk factors for the development of GVHD and the latter also influences on mortality and survival after allogeneic transplantation from HLA-identical donors.     

Evaluation of a semi-automated Seegene PCR workflow with MTB,MDR, and NTM detection for rapid screening of tuberculosis in a low-prevalence setting

In areas of low tuberculosis (TB) prevalence, laboratory diagnosis of TB may essentially cover non-tuberculous mycobacteria (NTM) in addition to Mycobacterium tuberculosis (MTB). In this study, a semi-automated PCR workflow distinguishing MTB and NTM (Anyplex™ MTB/NTMe, Seegene) and subsequently detecting MTB isoniazid/rifampicin resistance (Allplex™ MTB/MDRe, Seegene) was evaluated for replacing smear microscopy of acid-fast bacilli as the rapid screening method for TB. With 279 clinical samples, 47 cultures positive for MTB and 76 for NTM, the Anyplex™ MTB/NTMe assay and smear microscopy showed equal sensitivities (49.6% vs 50.8%, respectively) but Anyplex™ MTB/NTMe was more sensitive for MTB (63.8% vs 25.6%) than for NTM (40.8% vs 64.5%). Allplex™ MTB/MDRe showed a slightly higher sensitivity of 68.1% for MTB (32/47 positive, n = 222). Antibiotic resistance profiles were correctly identified for all MTB isolates (one MDR isolate). Specificity was 100% for both assays. Anyplex™ MTB/NTMe detected all the 18 NTM species present in the study. The analytical performance of the evaluated high-throughput workflow was relatively weak compared to culture but potentially adequate as a rapid screening method analogous to smear microscopy with additional differentiation between TB, MDR-TB, and NTM.     

Mycobacterial pulmonary infections in patients with idiopathic pulmonary fibrosis

Patients with idiopathic pulmonary fibrosis (IPF) have an increased risk for developing tuberculosis (TB). However, no studies have been reported regarding the development of nontuberculous mycobacterium (NTM) lung disease (NTMLD). We reviewed 795 patients with IPF from five university hospitals who were diagnosed by histological or radio-clinical criteria. In the 795 patients with IPF, pulmonary infections with mycobacterium tuberculosis (MTB) and NTM were found in 35 (4.4%) and 16 patients (2.0%), respectively, which was a higher frequency than that found in the general population. TB was more common in patients treated with immunosuppressants than in those who did not receive immunosuppressants (2.6% vs 1.4%, P = 0.12). Among the IPF patients who had mycobacterial infections,immunosuppressant users developed TB or NTMLD within 1 yr after treatment with immunosuppressants,while those occurred later than 2 yr after diagnosis of IPF in the subjects that did not receive immunosuppressants. Among 51 IPF patients who had mycobacterial infections, 9 (18%) died during follow-up. Of these, three died due to progression of pulmonary tuberculosis. TB and NTMLD is relatively common in patients with IPF in Korea and may be fatal in some groups. Careful evaluation of TB and NTMLD is necessary not only for immunosuppressant users, but also for nonusers with IPF.     

Long-Term Outcomes of Hematopoietic Stem Cell Transplantation for Severe Treatment-Resistant Autoimmune Cytopenia in Children

We analyzed the long-term outcomes of pediatric patients registered in the European Group for Blood and Marrow Transplantation database who underwent hematopoietic stem cell transplantation (HSCT) for severe treatment refractory autoimmune cytopenia. With a median follow-up of 100 months, event-free survival was 54% overall, with no significant difference between allogeneic HSCT (n = 15) and autologous HSCT (n = 7) recipients (58% versus 42%; P = .50). Despite a trend toward failure of response or relapse after autologous HSCT compared with allogeneic HSCT, the difference was not significant (43% versus 13%; P = .30). Treatment-related mortality was high in both HSCT groups (29% and 16%; P = .09). Based on the limited numbers of subjects in this retrospective analysis, both allogeneic and autologous HSCT may induce complete and persistent responses in approximately one-half of pediatric patients with severe refractory autoimmune cytopenia, although treatment-related toxicity is high.     

Superior Survival of Unmanipulated Haploidentical Hematopoietic Stem Cell Transplantation Compared with Chemotherapy Alone Used as Post-Remission Therapy in Adults with Standard-Risk Acute Lymphoblastic Leukemia in First Complete Remission

We wanted to compare the efficacy of haploidentical hematopoietic stem cell transplantation (HSCT) with chemotherapy alone in adults with standard-risk acute lymphoblastic leukemia (ALL) in first complete remission (CR1). One hundred thirty-eight consecutive adult patients with standard-risk ALL in CR1 were retrospectively investigated. Of these patients, 59 received chemotherapy alone (group A) and 79 received unmanipulated haploidentical HSCT (group B). Cumulative incidence of relapse at 5 years in group A was significantly higher than that in group B (66.3% versus 29.9%, P < .0001). Overall and disease-free survival in group A were significantly inferior to group B (P < .0001). Moreover, multivariate analyses demonstrated that central nervous system leukemia (P = .002), T cell immunophenotype (P = .044), expression of E2A-PBX1 (P = .007), and positive minimal residual disease after the first cycle of consolidation (P = .004) were correlated with relapse. Patients with 1 of 4 risk factors were assigned to the high-risk group. Otherwise, patients without risk factors were assigned to the low-risk group. In the high-risk group, HSCT had lower relapse rates and superior DFS compared with chemotherapy (P < .05), but in the low-risk group, there were no differences between HSCT and chemotherapy (P > .05). This study is the first to demonstrate that compared with chemotherapy alone, haploidentical HSCT is a better postremission therapy in adults with standard-risk ALL in CR1. Moreover, based on the 4 risk factors, the establishment of risk stratification could identify the subgroup of patients with a higher risk of relapse in adults with standard-risk ALL in CR1. Furthermore, risk stratification–directed postremission therapies using haploidentical HSCT or chemotherapy alone not only reduce relapse rate but also avoid unnecessary treatment-related mortality and improve survival.     

Elevated Numbers of Immature/Transitional CD21− B Lymphocytes and Deficiency of Memory CD27+ B Cells Identify Patients with Active Chronic Graft-versus-Host Disease

Chronic graft-versus-host disease (cGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (HSCT) and a leading cause of non-relapse mortality (NRM). Currently, biology-based markers are lacking both for diagnosis and for monitoring the activity of cGVHD. Seventy patients who received HSCT were enrolled in a pilot study, including 21 without cGVHD and 49 with active or resolved cGVHD. Evaluations were comprised of clinical parameters including cGVHD severity and infections. Peripheral blood cells were analyzed by multi-parameter flow cytometry. The CD19⁺ B cell compartment was further subdivided by staining for surface IgD, CD21 and CD27. No significant differences in absolute B, T, and natural killer (NK) cell numbers were observed between the groups with and without cGVHD. However, elevated numbers (>15% of B lymphocytes) of immature/transitional CD19⁺/CD21^- B cells were associated with the occurrence of severe infections (P = .003). Most significantly, all patients with active cGVHD and elevated numbers of CD19⁺/CD21^- B lymphocytes experienced severe infections (P = .00016). The numbers of both non-class-switched and class-switched memory B cells were significantly lower in patients with active cGVHD when compared to patients who never experienced cGVHD (P = .002 and P = .001). Perturbation of circulating B lymphocyte compartments may serve as a novel biomarker for monitoring cGVHD activity and its impact on the immune system. A prospective study on unselected patients assessed serially for B cell reconstitution after HSCT is warranted.     

Haploidentical haematopoietic stem cell transplantation for the treatment of severe aplastic anaemia patients with high-risk factors who lack an HLA-matched sibling donor

This study aimed to analyse the efficacy of haploidentical donor (HID) haematopoietic stem cell transplantation as a first-line treatment for severe aplastic anaemia (SAA) with high-risk factors (infection or very severe aplastic anaemia,VSAA) in patients who lack an HLA-matched sibling donor (MSD). The patients with infection were treated with anti-infection therapy, and allogeneic haematopoietic stem cell transplantation (HSCT) was carried out after the infection being effectively controlled was in accordance with the stable infection (SI) standard. A total of 44 SAA patients receiving MSD transplantation (n = 19) and HID transplantation (n = 25) were included in this study. There was no significant difference in neutrophil engraftment between the two groups [MSD vs. HID, 19 (11–38) vs. 22 (15–47).P = 0.241], and the difference in platelet engraftment was statistically significant [MSD vs. HID, 11(7–33) vs. 20 (12–69), P = 0.034]. The HID group exhibited a higher incidence of grade II–IV acute graft-versus-host disease (aGVHD) (HID vs. MSD, 48.0% vs10.5%, P = 0.034)and a higher incidence of chronic GVHD (cGVHD) than the MSD group (64.0% vs. 21.1%, P = 0.026). There was no significant difference between overall survival (OS) following HID and MSD transplantation (84.0% vs. 89.5%, P = 0.664) and failure-free survival (FFS)(80.0% vs. 84.2%, P = 0.965). The interval from diagnosis to transplantation (> 50d) and ECOG (> 2) were independent factors associated with OS and FFS. HID HSCT may be an effective and safe option for SAA patients with high-risk factors who lack an MSD.     

High within-host diversity found from direct genotyping on post-mortem tuberculosis specimens in a high-burden setting

ObjectivesTo characterize the clonal complexity in Mycobacterium tuberculosis (MTB) infections considering factors that help maximize the detection of coexisting strains/variants.MethodsGenotypic analysis by Mycobacterial Interspersed Repetitive-Unit–Variable-Number Tandem-Repeats (MIRU-VNTR) was performed directly on 70 biopsy specimens from two or more different tissues involving 28 tuberculosis cases diagnosed post-mortem in Mozambique, a country with a high tuberculosis burden.ResultsGenotypic data from isolates collected from two or more tissues were obtained for 23 of the 28 cases (82.1%), allowing the analysis of within-patient diversity. MIRU-VNTR analysis revealed clonal diversity in ten cases (35.7%). Five cases showed allelic differences in three or more loci, suggesting mixed infection with two different strains. In half of the cases showing within-host diversity, one of the specimens associated with clonal heterogeneity was brain tissue.ConclusionsDirect MTB genotyping from post-mortem tissue samples revealed a frequent within-host Mycobacterium tuberculosis diversity, including mixed and polyclonal infections. Most of this diversity would have been overlooked if only standard analysis of respiratory specimens had been performed.     

Extramedullary Relapse of Acute Leukemia after Haploidentical Hematopoietic Stem Cell Transplantation: Incidence,Risk Factors,Treatment, and Clinical Outcomes

We examined the incidence, risk factors, treatment, and clinical outcomes of extramedullary relapse (EMR) in 961 acute leukemia patients undergoing HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) between 2002 and 2013. Multiple control subjects were selected at random from the same cohort and matched to EMR cases for diagnosis, disease status at HSCT, age at the time of the HSCT, and year of HSCT. Forty patients exhibited EMR, with a median time to EMR of 207 days. The cumulative incidence of EMR was 4.0% at 3 years, and the incidence was higher in acute lymphoblastic leukemia patients compared with acute myeloid leukemia patients (5.6% versus 2.4%). In the multivariate analysis, non–complete remission (CR) status at HSCT (hazard ratio [HR] = 4.6; P = .018) and non–chronic graft-versus-host disease after HSCT (HR = 3.2; P < .001) were the independent risk factors for EMR after haplo-HSCT. Twenty-seven patients received combination treatments, and the proportion of patients who achieved CR was higher than those who received single treatment. Multifocal involvement at EMR (HR = 2.7; P = .024) and non-CR after EMR treatments (HR = 4.6; P < .001) were the independent risk factors for poor survival rates among EMR patients. We found that graft-versus-leukemia effect may help to prevent EMR after haplo-HSCT.     

Drug susceptibiity testing of nontuberculous mycobacteria by broth microdilution method

Introduction-Incidence of Nontuberculous mycobacteria (NTM) has been increasing in past few years. Treatment of NTM differs from Mycobacterium tuberculosis. For proper treatment, it's important to carry out Drug Susceptibility Testing of NTM. Method of DST for NTM is different from MTB and is not available in most laboratories.Method-We performed DST on 122 isolates of NTM. Amikacin, Ciprofloxacin, Trimethoprim, Doxycycline, Moxifloxacin, Clarithromycin, Minocycline and Cefoxitin were used for Rapid Growing Mycobacteria (RGM) and Rifampicin, Clarithromycin, Ethambutol, Isoniazid and Moxifloxacin for Slow Growing Mycobacteria (SGM). M. avium Complex (MAC) was tested against Clarithromycin. Minimum inhibitor concentration was calculated as recommended by standard Clinical and Laboratory Standards Institute (CLSI) and Resazurin Microtitre Assay (REMA).Result-Most of Rapid Growing Mycobacteria were sensitive to Amikacin (76.1%) and Moxifloxacin (46.47%) while Slow Growing Mycobacteria showed only 33.3% sensitivity to Rifampicin and Moxifloxacin and 42% to Clarithromycin. M. avium-intracellulare complex showed 45–50% sensitivity to Clarithromycin. Overall, 98% concordance (Kappa = 0.98; almost perfect; 95% CI = 0.966 to 0.996) was seen between standard and REMA method of DST of NTM.Conclusion-Rapid growers showed good sensitivity to Amikacin and Moxifloxacin, while only one third SGM showed sensitivity to Rifampicin, Moxifloxacin and Clarithromycin. For proper management of NTM of eastern Rajasthan its important to know the DST profile in our area to initiate empirical therapy till the results of specific patient are available. REMA was found to give excellent concordance with standard method.     

Molecular epidemiology of Escherichia coli causing bloodstream infections in a centralized Canadian region: a population-based surveillance study

ObjectivesEscherichia coli is a leading cause of bloodstream infections worldwide, and is responsible for substantial patient morbidity, mortality and healthcare expenditure. Understanding the molecular epidemiology of E. coli will aid in designing superior treatment and prevention strategies.MethodsWe undertook a population-based surveillance study describing the clinical factors, susceptibility patterns, incidence rates and geographical distribution of sequence types (STs) among E. coli isolates (n = 686) causing incident bloodstream infections in a centralized Canadian region during 2016. STs were identified using a seven-single-nucleotide-polymorphism quantitative PCR (n = 422) and sequencing of certain house-keeping genes (n = 249).ResultsThe annual population incidence rate of E. coli bloodstream infections was 48.8/100 000 patient years, and five dominant clones (ST131, ST73, ST69, ST95 and ST1193) accounting for 55% (378/686) of the population were identified, each with a specific geographical distribution within Calgary. ST131 was the most common (overall incidence rate of 10.4/100 000 patient years), an antimicrobial-resistant (AMR) clone affecting mainly the elderly and the very young. ST131 was common among residents in long-term care with an incidence rate of 312.5/100 000 patient years. ST73 was associated with community infections in the elderly, while ST69 and ST95 had increased incidence rates among females. ST1193 was the second most AMR clone and was associated with bloodstream infections in elderly males.ConclusionsThis study showed that E. coli clones have unique characteristics in a well-defined human population. The elimination of ST131 would substantially decrease the overall incidence rate and AMR burden among E. coli bloodstream infections in the Calgary region, leading to considerable public health benefits.     

Cytogenetics,Donor Type,and Use of Hypomethylating Agents in Myelodysplastic Syndrome with Allogeneic Stem Cell Transplantation

We investigated the impact of patient and disease characteristics, including cytogenetics, previous therapy, and depth of response, on the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) for patients with myelodysplastic syndrome (MDS). We analyzed 256 MDS patients who underwent transplantation from a matched related (n = 133) or matched unrelated (n = 123) donor after 2001. Of the 256, 78 (30.5%) did not receive cytoreductive therapy before HSCT; 40 (15.6%) received chemotherapy, 122 (47.7%) received hypomethylating agents (HMA), and 16 (6.2%) received both (chemo+HMA). Disease status at HSCT defined by International Working Criteria was complete remission in 46 (18%) patients. There were significant differences between therapy groups: there were more therapy-related MDS and higher use of matched related donor in the untreated group. The chemotherapy group had higher serum ferritin levels at HSCT. Patients were older and had more high-risk disease by revised International Prognostic Scoring in the HMA group. Despite those differences, transplantation outcomes were similar in patients who were untreated and who received cytoreductive therapy before HSCT. Three-year event-free survival (EFS) was 44.2%, 30.6%, 34.2%, and 32.8% for untreated, chemotherapy, HMA, and chemo+HMA groups, respectively (P = .50). Multivariate analyses revealed that older age (hazard ratio [HR], 1.3; P = .001); high-risk histologic subtypes, including refractory anemia with excess blasts (HR, 1.5; P = .05) and chronic myelomonocytic leukemia (HR, 2.1; P = .03), high-risk cytogenetics with monosomal karyotype (MK) (HR, 4.0; P < .0001) and high serum ferritin level at HSCT (HR, 1.8; P = .002) were poor prognostic factors for EFS. Bone marrow blast count 5% or higher at HSCT (HR, 1.6; P = .01) and MK (HR, 4.2; P < .0001) were the only prognostic factors for increased relapse incidence after HSCT. Patients with MK represented a poor prognostic group, with 3-year EFS of 11.4% and relapse incidence of 60.9%. In this analysis, various therapy approaches before HSCT did not lead to different transplantation outcomes. Cytogenetics defined by MK was able to identify a very poor prognostic groups that innovative transplantation approaches to improve outcomes are urgently needed.