Clinical Effectiveness of Conjugate Pneumococcal Vaccination in Hematopoietic Stem Cell Transplantation Recipients

Hematopoietic stem cell transplantation (HSCT) recipients are vulnerable to invasive pneumococcal disease (IPD), with reported IPD rates ranging from 3.81 to 22.5/1000 HSCT. This IPD risk could relate to immunodeficiency, low vaccination uptake, and poor immunogenicity of pneumococcal polysaccharide vaccine (PPV). Literature comparing the clinical effectiveness of pneumococcal conjugate vaccination (PCV) and PPV after HSCT is limited. In this retrospective analysis of HSCT recipients at our center from 2004 to 2015, we evaluated vaccination uptake and compared IPD rates in patients receiving PPV (pre-2010 group) and PCV (post-2010 group). IPD was determined from microbiological results for all HSCT recipients from January 2004 to June 30, 2019. Eight hundred patients had a total of 842 HSCT events, including autologous HSCT (auto-HSCT; n = 562) and allogeneic HSCT (allo-HSCT; n = 280). More than 90% of the HSCT recipients were enrolled, and >93% of surviving HSCT recipients completed the vaccination protocol. Fifteen IPD episodes occurred in 13 patients between 2004 and June 30, 2019. Thirteen episodes occurred in the pre-2010 group, even though 9 of 13 (69%) serotyped isolates were covered by PPV. Two episodes occurred in the post-2010 group; neither serotype was covered by PCV. Thus, with PCV introduction, IPD rate was significantly reduced from 38.5/1000 unique HSCTs pre-2010 to 4.0/1000 unique HSCTs post-2010 (P < .001). A significant reduction was seen in both auto-HSCTs (from 29.4 to 3.1 /1000 unique auto-HSCTs; P = .011) and allo-HSCTs (from 58.3 to 5.6/1000 unique allo-HSCTs; P = .011). PCV demonstrated superior clinical effectiveness over PPV, highlighting its importance in preventing infectious complications after HSCT. Robust vaccination programs at transplantation centers are needed to optimize vaccination uptake and completion.     

Therapeutic Impact and Complications Associated with Surgical Lung Biopsy after Allogeneic Hematopoietic Stem Cell Transplantation in Children

Hematopoietic stem cell transplantation (HSCT) in the pediatric population is associated with pulmonary complications in 25% of recipients. The role of surgical lung biopsy (SLB) remains unclear because of concerns about both the therapeutic impact and morbidity associated with the procedure. A retrospective review of consecutive allogeneic HSCT recipients at Dana-Farber and Boston Children's Hospital Cancer and Blood Disorders Center between 2006 and 2016 was performed. All recipients who underwent SLB during the study period were identified and charts reviewed for perioperative complications, histopathologic findings, and changes in therapy delivered. Pearson's chi-square test and Student's t-test (or appropriate nonparametric test) were used to evaluate the associations between perioperative complication and categorical and continuous variables, respectively. Five hundred fifty-five HSCTs were included, among which 48 SLBs (8.6%) were identified. Median follow-up time was 24 months (range, 0 to 139). Thirty-day postoperative morbidity was 16.7% and 30-day postoperative mortality 10.4% (n = 5). The overall 30-day postoperative complication rate (including mortality) was 20.8% (n = 10). No mortalities were directly attributable to SLB. Definitive diagnoses were identified in 70.8% of SLBs (n = 34), and therapeutic changes occurred in 79.2% (n = 38). Overall, 83.3% of SLBs (n = 40) either provided a diagnosis or led to a change in therapy. SLB has an acceptable risk of perioperative complications in this medically complicated and often severely ill population. In most HSCT patients, SLB aids in defining the etiology of pulmonary infiltrates and can inform therapeutic decisions in patients where noninvasive diagnostic modalities have failed to provide a definitive diagnosis.     

De-Escalation and Discontinuation of Empirical Antibiotic Treatment in a Cohort of Allogeneic Hematopoietic Stem Cell Transplantation Recipients during the Pre-Engraftment Period

To investigate rates and outcomes of antibiotic de-escalation during pre-engraftment neutropenia in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. 110 consecutive HSCTs performed between January 2013 and March 2014 were analyzed. De-escalation was defined as narrowing the spectrum of antibiotic treatment either within (early) or after 96 hours (late) from starting antibiotics. Discontinuation, considered a form of de-escalation, was defined as stopping antibiotics before engraftment. De-escalation failure was defined as restarting/escalating antibiotics within 96 hours after de-escalation. Predictors of de-escalation were analyzed. Among 102 patients who started antibiotics and were included, 68 (67%) received monotherapy (mainly piperacillin-tazobactam, n?=?58), whereas 34 (33%) received combination therapy (mainly meropenem plus glycopeptide, n?=?24). Median duration of neutropenia was 17 days. Bloodstream infections (BSIs) were diagnosed in 28 patients (20%). Early de-escalation rate was 25.5% (n?=?26) and mostly consisted of reducing the spectrum of β-lactams (n?=?11, 42%). In comparison with theoretical scenario of continuing therapy until engraftment, the median savings in terms of antibiotic days were 10 for meropenem, 8 for piperacillin-tazobactam, and 7 for vancomycin. Failure rate of early de-escalation was 15% (4/26). Late de-escalation rate was 30.4% (n?=?31) and failure rate 19% (6/31). The rate of de-escalation any time before engraftment was 55.9% (n?=?57), including discontinuation in 33 patients (32%). Death at day 60 after HSCT occurred in 3 patients who never underwent de-escalation. Acute myeloid disease and BSIs were independent predictors of early de-escalation. De-escalation, including discontinuation, is feasible and safe in pre-engraftment neutropenia after allogeneic HSCT.     

A Comparison of Bronchoalveolar Lavage versus Lung Biopsy in Pediatric Recipients after Stem Cell Transplantation

Bronchoalveolar lavage (BAL) has been a useful initial diagnostic tool in the evaluation of pulmonary complications after hematopoietic stem cell transplantation (HSCT); however, the diagnostic sensitivity, prevalence, and outcome after BAL versus lung biopsy (LB) in pediatric HSCT patients remains to be determined. We reviewed 193 pediatric HSCT recipients who underwent a total of 235 HSCTs. Sixty-five patients (34%) underwent a total of 101 BALs for fever, respiratory distress, and/or pulmonary infiltrates on chest radiograph and/or computed tomography scan. The 1-year probability of undergoing BAL was 43.0% after allogeneic stem cell transplantation (alloSCT) and 8.5% after autologous stem cell transplantation (autoSCT) (P = .001). Sixteen of the 193 patients (8%) patients underwent 19 LBs. The probability of undergoing LB at 1 year after HSCT was 9.3%. No grade III or IV adverse events related to either procedure were observed. Of the 101 BALs performed, 40% (n = 40) were diagnostic, with a majority revealing a bacterial pathogen. Among the 19 LBs performed, 94% identified an etiology. In multivariate analysis, myeloablative conditioning alloSCT conferred the highest risk of requiring a BAL (hazard ratio [HR],8.5; P = .0002). The probability of 2-year overall survival was 20.2% in patients who underwent BAL, 17.5% for patients who underwent biopsy, and 67.4% for patients who had neither procedure. In multivariate analysis, only the requirement of a BAL was independently associated with an increased risk of mortality (HR, 2.96; P < .0001). In summary, in this cohort of pediatric HSCT recipients, BAL and LB were used in approximately 35% and 8% of pediatric HSCTs with diagnostic yields of approximately 40% and 94%, respectively, and were both associated with poor long-term outcomes.     

Safety and Seropositivity after Live Attenuated Vaccine in Adult Patients Receiving Hematopoietic Stem Cell Transplantation

Vaccination against vaccine-preventable diseases (VPDs) is highly recommended for hematopoietic stem cell transplantation (HSCT) recipients by several guidelines; however, the safety and seropositivity after live attenuated vaccines remain unclear in adult HSCT recipients. We analyzed titers of antibodies against measles, rubella, mumps, and varicella zoster virus (VZV) from Japanese adult patients who underwent allogeneic HSCT (allo-HSCT) (n = 74), autologous HSCT (auto-HSCT) (n = 39), or chemotherapy (n = 93). The seropositive rates for measles, rubella, mumps, and VZV in allo-HSCT recipients were 20.2%, 36.4%, 5.4%, and 55.4%, respectively. These rates were equivalent to those in auto-HSCT recipients but were significantly lower than those in patients receiving chemotherapy. Antibody titers tended to gradually decrease with time. Twenty-nine allo-HSCT recipients and 8 auto-HSCT recipients received live attenuated vaccines against VPDs for which they tested seronegative. The titers of antibodies against measles, rubella, and mumps significantly increased after 2 shots of vaccine, and the seropositive rate increased up to 19%, 30%, and 27%, respectively. Three patients (8.1%) experienced mild adverse events, which resolved promptly, indicating safe administration of the live attenuated vaccines. In multivariate analysis, history of chronic graft-versus-host disease was significantly associated with high seropositivity for measles as well as high seroconversion rate for measles after vaccination. Live attenuated vaccines against VPDs were safely administered in seronegative adult HSCT recipients. A further observational study is crucial to evaluate the efficacy of vaccination in seronegative HSCT patients.     

Evaluation of Chimerism Dynamics after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Nonmalignant Diseases

It is recognized that chimerism following hematopoietic stem cell transplantation (HSCT) is a dynamic process. The aims of this study were to describe the evolution of chimerism in children with nonmalignant diseases who underwent allogeneic HSCT, and to analyze the risk factors influencing chimerism status. A total of 101 HSCTs were performed in 85 patients with nonmalignant diseases. The donor was unrelated in 62.4% of HSCTs. Reduced-intensity conditioning (RIC) regimen was administered in 48.5% of patients. Acute graft-versus-host disease (aGVHD) occurred in 51.7% and chronic GVHD (cGVHD) in 39.7% of patients. Analysis of chimerism was performed through amplification of 9 specific short tandem repeats by polymerase chain reaction at engraftment and 1, 6, and 12 months after HSCT. Upon first evaluation, complete chimerism (CC) was detected in 34.7% and mixed chimerism (MC) in 55.4%, whereas graft failure occurred in 9.9% of patients. Severe aGVHD was associated with CC (P?=?.031). The last chimerism evaluation showed CC in 72.1%, stable MC in 12.8%, and progressive MC in 3.5%. CC was associated with a higher incidence of aGVHD (P?=?.016) and cGVHD (P?=?.022), whereas the RIC regimen was associated with graft failure (P?=?.026). One- and 3-year overall survival (OS) was 87.4% and 80.5%, respectively, with a lower OS at 3 years in patients with CC compared with those with MC (P?=?.008). aGVHD and cGVHD represent factors favoring CC, thus close, careful follow-up of chimerism is recommended in patients affected by nonmalignant disease.     

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.     

Risk Factors and Predictive Scoring System For Post-Transplant Lymphoproliferative Disorder after Hematopoietic Stem Cell Transplantation

We analyzed data from 64,539 consecutive patients in the Japanese national transplant registry, including 40,195 after allogeneic hematopoietic stem cell transplantation (HSCT), 24,215 after autologous HSCT and 129 after syngeneic HSCT, of whom 299 developed Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (PTLD). The probability of developing PTLD at 2 years post-HSCT was .79% after allogeneic transplantation, .78% after syngeneic transplantation, and .11% after autologous transplantation. The following variables were identified as risk factors after allogeneic HSCT in multivariate analysis: antithymocyte globulin (ATG) use in a conditioning regimen, ATG use for acute graft-versus-host disease (GVHD) treatment, donor other than an HLA-matched related donor, aplastic anemia, second or subsequent allogeneic HSCT, the most recent year of transplantation, and acute GVHD. The probability at 2 years increased particularly after 2009 (1.24%) than before 2009 (.45%). To stratify the risk of PTLD before allogeneic HSCT, we developed a novel 5-point scoring system based on 3 pretransplant risk factors: ATG use in a conditioning regimen (high dose, 2 points; low dose, 1 point), donor type (HLA-mismatched related donor, 1 point; unrelated donor, 1 point; cord blood, 2 points), and aplastic anemia (1 point). Patients were classified into 4 risk groups according to the summed points: low risk (0 or 1 point), intermediate risk (2 points), high risk (3 points), and very high risk (4 or 5 points) groups, with probabilities at 2 years of .3%, 1.3%, 4.6%, and 11.5%, respectively. Our scoring system is useful for predicting patients at high risk for PTLD. Careful observation and close monitoring of Epstein-Barr virus reactivation are warranted for these high-risk patients.     

Results of Allogenic Hematopoietic Stem Cell Transplantation in Fanconi Anemia Caused by Bone Marrow Failure: Single-Regimen,Single-Center Experience of 14 Years

Hematopoietic stem cell transplantation (HSCT) is the only curative treatment for bone marrow failure (BMF) in patients with Fanconi anemia (FA). We retrospectively analyzed the records of patients with FA who underwent HSCT with a radiation-free, reduced-intensity conditioning regimen (fludarabine, cyclophosphamide, and antithymocyte globulin) along with an unmanipulated graft infusion between 2004 and 2018. A total of 44 patients underwent HSCT during the study period. Median age at transplantation was 121 months. Regarding the donor source, 22 transplants (50%) were collected from matched related donors (MRDs), and 22 transplants (50%) were collected from alternative donors (ADs). The median infused CD34⁺ cell dose was 4.7 × 10⁶/kg (range, 0.8 to 23) in bone marrow or peripheral blood stem cell recipients and 1.2 × 10⁵/kg (range, 1.1 to 3.6) in umbilical cord blood recipients. All but 2 patients achieved primary neutrophil engraftment (95%). In a median follow-up of 36 months (range, 1 to 159), 3-year overall survival was 70.5% in the entire group and 91% in the MRD recipients. Primary causes of death were infections (n = 5), acute grade 3 to 4 graft-versus-host disease (n = 4), and hemorrhagic cystitis (n = 3). All surviving patients have full (n = 29) and acceptable mixed (n = 2) donor chimerism and good clinical status. Our results showed an excellent outcome with unmanipulated grafts using a fludarabine-based, radiation-free preparative regimen for MRD recipients. Even though primary neutrophil engraftment rates were good in AD recipients, intervening complications increased mortality in these patients. In clinics where T cell depletion is not feasible, more effort is warranted to improve outcomes for AD recipients.     

Lifetime Probabilities of Hematopoietic Stem Cell Transplantation in the U.S.

Healthcare policies regarding hematopoietic stem cell transplantation (HSCT) must address the need for the procedure as well as the availability of stem cell sources: bone marrow, peripheral blood, or umbilical cord blood (UCB). However, data with respect to the lifetime probability of undergoing HSCT are lacking. This study was undertaken to estimate the latter probability in the United States (U.S.), depending on age, sex, and race. We used data from the Center for International Blood and Marrow Transplant Research, the U.S. Surveillance, Epidemiology and End Results Program, and the U.S. Census Bureau and calculated probabilities as cumulative incidences. Several scenarios were considered: assuming current indications for autologous and allogeneic HSCT, assuming universal donor availability, and assuming broadening of HSCT use in hematologic malignancies. Incidences of diseases treated with HSCT and of HSCTs performed increase with age, rising strongly after age 40. Among individuals older than 40, incidences are higher for men than for women. The lifetime probabilities of undergoing HSCT range from 0.23% to 0.98% under the various scenarios. We conclude that, given current indications, the lifetime probability of undergoing autologous or allogeneic HSCT is much higher than previously reported by others and could rise even higher with increases in donor availability and HSCT applicability.     

Hematopoietic Stem Cell Transplantation Without the Use of Blood Components by the Patient's Choice: Experience of 2 Brazilian Centers

Hematopoietic stem cell transplantation (HSCT) has been used to treat many malignant and nonmalignant hematologic conditions; however, the use of HSCT in patients who refuse blood transfusions has rarely been described in the literature, and no data have been published concerning haploidentical HSCT without the use of blood products. The aim of this study is to describe the experience of a Brazilian group in performing 21 HSCTs without the use of blood components in the first 100 days after transplantation, which is the period corresponding to the greatest risk of toxicity for this procedure. We developed 21 HSCTs without transfusion support in 19 patients admitted to 2 Brazilian transplantation centers. The patients were subjected to stem cell mobilization and different conditioning regimens. No mortality related to the procedure occurred among the transplant recipients. The global survival rate after 100 days, which is the period related to the immediate toxicity of HSCT, was 94.7%, and the median duration of follow-up was 980 days, with an overall survival rate of 68.4%. Thus, refusal of blood transfusion is not an absolute contraindication for HSCT. This therapy is feasible in specific situations when the patient clearly expresses a desire to avoid blood transfusions and when favorable clinical conditions are achievable with strict, specialized medical monitoring.     

Outcomes of Children with Hemophagocytic Lymphohistiocytosis Given Allogeneic Hematopoietic Stem Cell Transplantation in Italy

We report on 109 patients with hemophagocytic lymphohistiocytosis (HLH) undergoing 126 procedures of allogeneic hematopoietic stem cell transplantation (HSCT) between 2000 and 2014 in centers associated with the Italian Pediatric Hematology Oncology Association. Genetic diagnosis was FHL2 (32%), FHL3 (33%), or other defined disorders known to cause HLH (15%); in the remaining patients no genetic abnormality was found. Donor for first transplant was an HLA-matched sibling for 25 patients (23%), an unrelated donor for 73 (67%), and an HLA-partially matched family donor for 11 children (10%). Conditioning regimen was busulfan-based for 61 patients (56%), treosulfan-based for 21 (20%), and fludarabine-based for 26 children (24%). The 5-year probabilities of overall survival (OS) and event-free survival (EFS) were 71% and 60%, respectively. Twenty-six patients (24%) died due to transplant-related causes, whereas 14 (13%) and 10 (9%) patients experienced graft rejection and/or relapse, respectively. Twelve of 14 children given a second HSCT after graft failure/relapse are alive and disease-free. Use of HLA-partially matched family donors was associated with higher risk of graft failure and thus with lower EFS (but not with lower OS) in multivariable analysis. Active disease at transplantation did not significantly affect prognosis. These data confirm that HSCT can cure most HLH patients, active disease not precluding successful transplantation. Because in HLH patients HLA-haploidentical HSCT performed through CD34⁺ cell positive selection was found to be associated with poor sustained engraftment of donor cells, innovative approaches able to guarantee a more robust engraftment are warranted in patients given this type of allograft.     

Hematopoietic Stem Cell Transplant for Pediatric Acute Promyelocytic Leukemia

The optimal form of treatment for children with relapsed or refractory acute promyelocytic leukemia (APL) is unclear. We retrospectively analyzed the results of 32 (11 autologous, 21 allogeneic) hematopoietic stem cell transplants (HSCT) performed for children originally treated on either the Eastern Cooperative Group E2491 Trial or the Cancer and Leukemia Group B C9710 Trial and subsequently diagnosed with relapsed or refractory APL. For autologous HSCT, the incidence of treatment-related mortality (TRM) and relapse was 0% (95% confidence interval [CI], 0%-30%) and 27% (95% CI, 9%-57%), respectively. The 5-year event-free survival (EFS) and overall survival (OS) following autologous HSCT was 73% (95% CI, 43%-91%) and 82% (95% CI, 51%-96%), respectively. For allogeneic HSCT, the incidence of TRM and relapse was 19% (95% CI, 7%-41%) and 10% (95% CI, 2%-30%), respectively. The 5-year EFS and OS following allogeneic HSCT was 71% (95% CI, 50%-86%) and 76% (95% CI, 55%-90%), respectively. There was no significant difference in EFS or OS between autologous and allogeneic HSCT. This data demonstrates that autologous and allogeneic HSCT are both effective therapies for treatment of children with relapsed or refractory APL. Autologous HSCT is associated with a low incidence of TRM, whereas allogeneic HSCT is associated with a low incidence of relapse, suggesting a strong GVL effect against residual APL.     

Comparison of Characteristics of Bacterial Bloodstream Infection between Adult Patients with Allogeneic and Autologous Hematopoietic Stem Cell Transplantation

Although autologous and allogeneic hematopoietic stem cell transplantation (HSCT) are fundamentally different procedures, a tailored approach to bacterial bloodstream infection (BSI) according to the type of HSCT has not yet been suggested. We evaluated the characteristics of BSI after HSCT, with a focus on comparison of BSIs between recipients of autologous HSCT (auto-HSCT) and allogeneic HSCT (allo-HSCT). Among 134 patients (59 received allo-HSCT and 75 received auto-HSCT) who underwent HSCT, BSIs were reported earlier in patients who underwent auto-HSCT, compared with those who underwent allo-HSCT (mean 12.1 ± 3.4 days versus 32.8 ± 27.1 days, P = .006). Among patients receiving allo-HSCT, postneutrophil-engraftment bacterial BSI showed an association with grade ≥2 acute graft-versus-host disease (GVHD). In patients who underwent auto-HSCT, results of multivariate analysis showed that not receiving prophylactic antibiotics (P = .004) and having elevated serum C-reactive protein (P = .034) were risk factors of BSI. Elevated CRP (P = .01) and acute GVHD ≥ grade 2 (P = .002) were independent risk factors in patients who underwent allo-HSCT. Those differences originated mainly from the impact of acute GVHD-related postengraftment BSIs of patients who underwent allo-HSCT. To establish the best defense strategy against BSI, the distinctive natures of bacterial BSI after HSCT between auto-HSCT and allo-HSCT should be considered.     

Hematopoietic Stem Cell Transplantation in Patients Infected With HIV

Hematopoietic stem cell transplantation (HSCT) replaces a diseased hematopoietic system with a functional, disease-free graft and is frequently used in the treatment of hematologic malignancies. The advent of highly active antiretroviral therapy made it possible to treat medical conditions in HIV-infected patients in the same way as in the general population. Several studies have reported the feasibility, safety, and efficacy of autologous HSCT as rescue or consolidation treatment for non-Hodgkin’s and Hodgkin’s lymphoma in HIV-infected patients. As a result of the improvements in supportive care and the introduction of attenuated transplant conditioning regimens, allogeneic HSCT has been used to treat life-threatening hematologic disorders, with promising results in HIV-infected patients. Moreover, this strategy has made it possible to treat both the hematologic disease and HIV infection.     

Clostridium Difficile Infection after Allogeneic Hematopoietic Stem Cell Transplant: Strain Diversity and Outcomes Associated with NAP1/027

Allogeneic hematopoietic stem cell transplantation (HSCT) recipients are at high risk for developing Clostridium difficile infection (CDI). We studied the incidence, risk factors, NAP1/027 prevalence, and clinical outcomes, including acute lower gastrointestinal graft-versus-host disease (GI GVHD), associated with early CDI in this population. A retrospective review was conducted of patients who underwent allogeneic HSCT at Memorial Sloan Kettering Cancer Center from January 1, 2005 to September 30, 2010. Early CDI was defined as infection occurring from day −10 to day +40 from stem cell infusion. Among 793 patients who received allogeneic HSCTs, early CDI occurred in 11.9%; 56% cases were between day −5 and day +5. Overall incidence was 25.2 cases/10,000 at-risk days. There was a high prevalence of NAP1/027 strains during peak incidence (61% in 2008). NAP1/027 was the most common strain in both adult and pediatric cases (24% and 23%, respectively). CDI was clinically mild, including those due to NAP1/027. Metronidazole was the primary treatment for 91 of 94 patients, 7 of 8 cases refractory to metronidazole had no response to vancomycin, and none was due to NAP1/027. Relapse of CDI was common (31%). The cumulative incidence of GI GVHD in patients with and without early CDI was 6.8% and 8%, respectively (P = .5). Most cases of CDI occurred during conditioning or immediately after transplant. Despite high prevalence of NAP1/027, we found only mild disease. Most patients were treated successfully with metronidazole, irrespective of NAP1/027 status. There was no significant association between early CDI and subsequent development of GI GVHD. This study demonstrates the high incidence of CDI early after allogeneic HSCT with wide diversity among infecting strains. Despite the high prevalence of NAP1/027, the disease is mild but relapses are common. No association was found between CDI and subsequent development of GI GVHD.     

Prevalence of Ototoxicity Following Hematopoietic Stem Cell Transplantation in Pediatric Patients

The use of hematopoietic stem cell transplantation (HSCT) is increasing for a variety of diseases. Ototoxicity from this procedure has not been extensively studied. A retrospective chart review examined 275 patients from this institution who underwent HSCT between January 1, 2007, and April 30, 2017. Data extracted included therapy before HSCT and the subsequent course of transplantation. Evaluable patients had complete medical records and interpretable audiograms available. Ototoxicity constituted significant threshold changes from baseline or changes in International Society of Pediatric Oncology/Boston Ototoxicity Grading Scale (SIOP) grade comparing audiogram results just before HSCT with those following the transplantation procedure. A total of 147 patients were evaluable. Ototoxicity was observed in 10.2% of the patients. Higher SIOP grade before HSCT was significantly associated with a higher risk of post-transplantation ototoxicity (P < .01). Previous cisplatin treatment (P < .0001), but not carboplatin or radiation treatment, was also associated with ototoxicity. Patients with a solid tumor or brain tumor (P < .0001) and those who received an autologous transplant (P = .0002) were also at increased risk. No post-transplantation event was significantly associated with ototoxicity. Ototoxicity affects a significant percentage of patients undergoing HSCT, and careful monitoring is needed to identify patients impacted by this procedure.     

Noninfectious Neurologic Complications after Allogeneic Hematopoietic Stem Cell Transplantation

Although allogeneic hematopoietic stem cell transplantation (allo-HSCT) can be associated with neurologic complications, data on noninfectious etiologies are scanty. Therefore, we analyzed the incidence, clinical characteristics, risk factors, and influence on outcomes of noninfectious neurologic complications (NCs) in 971 consecutive patients with hematologic malignancies undergoing allo-HSCT at our center between January 2000 and December 2016. We evaluated NCs affecting the central nervous system (CNS) and peripheral nervous system (PNS). The median duration of follow-up of survivors was 71 months (range, 11 to 213 months). A total of 467 patients received a matched sibling donor (MSD) transplant, 381 received umbilical cord blood (UCB), 74 received a haploidentical transplant, and 49 received a matched unrelated donor (MUD) transplant. One hundred forty-nine (15.3%) NCs were documented at a median of 78 days after transplantation (range, 5 days before to 3722 days after). The cumulative incidence risk of developing NC was 7.5% (95% confidence interval, 6% to 8.2%) at day +90 and 13% at 5 years. The 5-year cumulative incidence of NCs was 10.8% after MSD allo-HSCT and 15.3% after alternative donor (UCB, MUD, haploidentical) allo-HSCT (P = .004). There were 101 (68%) CNS complications, including encephalopathy, n = 46 (31%); headache, n = 20 (13%); stroke, n = 15 (10%); seizures, n = 9 (6%), posterior reversible encephalopathy syndrome, n = 6 (4%), and myelopathy, n = 5 (3%). PNS complications (32%) included neuropathies, n = 25 (17%), and myopathies and neuromuscular junction disorders, n = 23 (17%), with 17% of the total PNS complications being immune-related. In multivariable analysis, donor type other than MSD, age ≥40 years, development of acute graft-versus-host disease (GVHD) grade II-IV (hazard ratio [HR], 3.3; P < .00001), and extensive chronic GVHD (HR, 3.2; P = .0002) were independently associated with increased risk of NCs. The 5-year overall survival (OS) was 21% in patients who developed NCs and 41% for those who did not (P < .0001). This difference in OS was observed in patients developing CNS NCs, but not in those developing PNS complications. In conclusion, our study reveals NCs as a frequent and heterogeneous complication that, when affecting CNS, is associated with poor prognosis following allo-HSCT.     

Identification and Characterization of Hematopoietic Stem Cell Transplant Candidates in a Sickle Cell Disease Cohort

Sickle cell disease (SCD) is associated with significant morbidity, and allogeneic hematopoietic stem cell transplantation (HSCT) remains the primary curative treatment. Recently, the Brazilian Ministry of Health released a regulation that required the publically funded healthcare system to pay for HSCT for SCD patients with defined indications. We used an existing 2794-member SCD cohort established during 2013 to 2015 to characterize candidates for HSCT and estimate the number of possible donors. Of 2064 patients with SC anemia (SCA), 152 of 974 children (16%) and 279 of 1090 adults (26%) had at least 1 HSCT indication. The most common indication for transplant was stroke (n = 239) followed by avascular necrosis (n = 96), priapism (n = 82), cerebrovascular disease (n = 55), >2 vaso-occlusive episodes (n = 38), alloantibodies and chronic transfusion therapy (n = 18), and >2 acute chest syndrome episodes (n = 11). Increasing age, number of transfusions, abnormal transcranial Doppler, retinopathy, dactylitis, and use of hydroxyurea were more frequent in the 152 children with an indication for HSCT compared with 822 without (P < .001). Of 152 children and 279 adults meeting the eligibility definition, 77 (50%) and 204 (73%), respectively, had at least 1 non-SCD full sibling who could potentially serve as a donor. In conclusion, in a large cohort of SCA patients, 16% of children and 26% of adults had at least 1 indication for HSCT; these indications were associated with the severity of the disease. This study provides clinical data necessary for estimating the costs and infrastructure that would be required to implement HSCT in a public healthcare system.     

Hematopoietic Stem Cell Transplantation in Adults with Acute Myeloid Leukemia

Hematopoietic stem cell transplantation (HSCT) is an integral part of the treatment of many patients with acute myeloid leukemia (AML). Despite extensive study, the appropriate role and timing of allogeneic and autologous transplantation in AML are poorly defined. This review critically analyzes the extensive literature, focusing on the recent advances, and provides practical recommendations for the use of HSCT in AML.