scholarly journals 2695. Pneumocystis jirovecii Pneumonia in the Era of Effective Prophylaxis Following Hematopoietic Stem Cell Transplant

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S947-S948
Author(s):  
Alexander Christian Drelick ◽  
Priya Kodiyanplakkal ◽  
Markus Plate ◽  
Michael J Satlin ◽  
Rosemary Soave ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Clinical Symptoms ◽  
Quantitative Polymerase Chain Reaction ◽  
Case Series ◽  
Pneumocystis Jirovecii ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Background Pneumocystis jirovecii pneumonia is an uncommon and life-threatening disease that can occur following hematopoietic stem cell transplantation (HSCT). Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis greatly reduces the incidence of PJP. We aim to determine what factors contribute to the development of PJP following HSCT where TMP-SMX prophylaxis is widely used. Methods We performed a single-center, retrospective case series of HSCT recipients from January 1, 2012 to December 31, 2018. Subjects had clinical symptoms and radiographic evidence for PJP along with at least one positive Pneumocystis test obtained from bronchoalveolar lavage (BAL) including direct fluorescence antibody (DFA), quantitative polymerase chain reaction (qPCR), cytology, and pathology. Results 1111 subjects underwent HSCT; of whom, 25 (2.2%) met inclusion criteria and were treated for PJP. 6 were autologous and 19 were allogeneic HSCT recipients (1.23% and 3.05% of total autologous and allogeneic HSCT, respectively). All allogeneic HSCT recipients received in-vivo T-cell depletion. Median duration from autologous and allogeneic HSCT to PJP diagnosis were 138 days (range 20 to 348) and 346 days (range 41 to 771), respectively. PJP qPCR was positive in all samples tested (n = 20, range < 84 to 14900). DFA was positive in 6 (28%). Death from pneumonia occurred in 2 subjects; 11 (44%) required ICU stay, and 7 (27%) required intubation. At diagnosis, 3 subjects had relapse of underlying disease and 10 were on immunosuppression. 12 were on PJP prophylaxis (autologous HSCT n = 3), the most common of which was atovaquone (n = 5); only 2 subjects were on TMP-SMX. Cytomegalovirus (CMV) viremia was detected in 9 subjects (36%) prior to PJP diagnosis; 4 had pulmonary CMV coinfection. In total, 17 subjects (68%) had one of the above risk factors for PJP. Median total lymphocyte count and % lymphocytes were 5.1 × 103 cells/μL (range 1.4 to 38.5 × 103 cells/μL) and 9.6% (range 1.1 to 29.5%), respectively. Conclusion PJP is an uncommon (2.2% of the study population) complication of HSCT while receiving PJP prophylaxis and in the absence of disease relapse, CMV reactivation, or ongoing immunosuppression. Presentation is often delayed in this population; a high degree of clinical suspicion should prompt diagnostic evaluation using a combination of laboratory tests on BAL fluid. Disclosures All authors: No reported disclosures.

scholarly journals Pentamidine for Prophylaxis against Pneumocystis jirovecii Pneumonia in Pediatric Oncology Patients Receiving Immunosuppressive Chemotherapy

2018 ◽  
Vol 62 (8) ◽  
Author(s):  
Melissa Quinn ◽  
J. T. Fannin ◽  
Joseph Sciasci ◽  
Allison Bragg ◽  
Patrick K. Campbell ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Pediatric Oncology ◽  
Pneumocystis Jirovecii ◽  
Drug Event ◽  
Pneumocystis Jirovecii Pneumonia ◽  
Cell Transplant ◽  
Oncology Patients ◽  
Hematopoietic Stem ◽  
Content Type

ABSTRACT Pneumocystis jirovecii pneumonia is a life-threatening opportunistic infection in children receiving immunosuppressive chemotherapy. Without prophylaxis, up to 25% of pediatric oncology patients receiving chemotherapy will develop Pneumocystis jirovecii pneumonia. Trimethoprim-sulfamethoxazole is the preferred agent for prophylaxis against Pneumocystis jirovecii pneumonia. Pentamidine may be an acceptable alternative for pediatric patients unable to tolerate trimethoprim-sulfamethoxazole. A retrospective review was conducted of pediatric oncology patients who received ≥1 dose of pentamidine for Pneumocystis jirovecii pneumonia prophylaxis between January 2007 and August 2014. Electronic medical records were reviewed to determine the incidence of breakthrough Pneumocystis jirovecii pneumonia or discontinuation of pentamidine associated with adverse events. A total of 754 patients received pentamidine prophylaxis during the period. There were no cases of probable or proven Pneumocystis pneumonia, and 4 cases (0.5%) of possible Pneumocystis pneumonia. The incidence of possible breakthrough Pneumocystis pneumonia was not significantly different between subgroups based on age (<12 months [1.7%] versus ≥12 months [0.4%], P = 0.3), route of administration (aerosolized [0%] versus intravenous [1.0%], P = 0.2), or hematopoietic stem cell transplant status (transplant [0.4%] versus no transplant [0.8%], P = 0.6). Pentamidine was discontinued due to an adverse drug event in 23 children (3.1%), more frequently for aerosolized than for intravenous administration (7.6% versus 2.2%, respectively, P = 0.004). Intravenous or inhaled pentamidine may be a safe and effective second-line alternative for prophylaxis against Pneumocystis jirovecii pneumonia in children with cancer receiving immunosuppressive chemotherapy or hematopoietic stem cell transplantation.

Early Hematopoietic Stem Cell Transplant Is Associated with Improved Outcomes in Children with MDS,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4126-4126
Author(s):  
Ellen C Christianson ◽  
Barb Trotz ◽  
Qing Cao ◽  
Emily Lipsitz ◽  
Brenda Weigel ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Factors Associated ◽  
Secondary Mds

Abstract Abstract 4126 Background: Childhood myelodysplastic syndrome (MDS) is a rare, heterogeneous disorder that is clinically distinct from adult MDS. Hematopoietic stem cell transplant (HSCT) is the treatment of choice, but there is no consensus regarding patient, disease, or treatment-related factors that predict outcomes after HSCT. Materials and Methods: We performed a retrospective review of 37 consecutive pediatric patients who received allogeneic HSCT for MDS at the University of Minnesota Amplatz Children's Hospital between 1990 and 2010. The median age at transplant was 11 years (range 1–21 years). Twenty patients had primary (de novo) MDS and 17 had secondary MDS (4 treatment-related, 8 with preceeding idiopathic aplastic anemia, 3 with Schwachman Diamond syndrome, and 2 familial). Those with Fanconi Anemia were excluded. Cytogenetics at diagnosis included monosomy 7 (n=21), trisomy 8 (n=7), normal/other (n=8). Thirty-one had refractory cytopenia (RC) and 6 had refractory anemia with excess blasts (RAEB) according to the modified WHO MDS classification. Patients were scored according to the International Prognostic Scoring System as low risk (n=1), intermediate-1 (Int-1; n=15), intermediate-2 (Int-2; n=21), or high risk MDS (n=0). Six patients received pre HSCT chemotherapy. Immediately prior to transplant, 27 had <5% bone marrow (BM) blasts and 10 had ≥ 5% blasts. Time from diagnosis to transplant was <140 days in 18 patients and ≥140 days in 19. Donor sources included umbilical cord blood (UCB; n=9), HLA-matched related donor (MRD; n=15), HLA-matched unrelated donor (MURD; n=7), and HLA-mismatched unrelated donor (MMURD; n=6). All patients received myeloablative conditioning prior to transplant (Cy/TBI n=35, Bu based n=2). The majority (70%) received cyclosporin based GVHD prophylaxis. Results: Neutrophil engraftment occurred in 89% (95%CI 77–97%) of patients at a median of 23 days (range 12–40). Patients transplanted after year 1999 were more likely to engraft (RR 2.27; 95% CI 1.06–4.88, p=.04). Overall survival (OS) was 70% (95%CI 53–82%) and 53% (95% CI 36–68%) at 1 and 3 years. In multivariate analysis (MVA), OS at 1 year was increased in patients who did not receive pre HSCT chemotherapy (RR of death 0.04; 95% CI 0–0.50, p=.01) and decreased in those with an IPSS score of Int-2 (RR of death 11.96; 95%CI 1.29–110.74, p=.03). Disease free survival (DFS) was 62% (95%CI 44–75%) and 48% (95% CI 31–63%) at 1 and 3 years. In MVA, factors associated with improved DFS at 3 years include having secondary MDS (RR of death or relapse 0.13; 95% CI 0.02–0.69 p=.02), undergoing HSCT after 1999 (RR 0.06; 95% CI 0.01–0.70, p=.02), not receiving pre HSCT chemotherapy (RR 0.06, 95% CI 0.01–0.36, p<.01), and a short interval (<140 days) from diagnosis to transplant (RR 0.21; 95% CI 0.05–0.85, p=.03). Those with an IPSS score of Int-2 had a significantly lower DFS (RR 3.96; 95% CI 1.12–14.00, p=.03). WHO classification, cytogenetics and pre HSCT blast percentage had no significant impact on either OS or DFS. The relapse rate at 2 years was 20% (95% CI 733%). Factors associated with decreased relapse include having secondary MDS (RR 0.04; 95% CI 0.01–0.21, p<.01) and not receiving pre HSCT chemotherapy (RR 0.21; 95% CI 0.05–0.85, p=0.03). Treatment-related mortality (TRM) was 25% (95%CI 11–39%) at 1 year. The risk of TRM was increased in patients with a pre HSCT blast count ≥ 5% (RR 6.65; 95% CI 1.60–27.67, p= 0.01) and was decreased in patients who did not receive pre HSCT chemotherapy (RR 0.07; 95% CI 0.01–0.69, P=.02). At 100 days the cumulative incidence of grades II-IV and III-IV acute graft versus host disease (GVHD) was 41% (95% CI 24–57%) and 16% (95% CI 5–28%), respectively. The incidence of chronic GVHD at one year was 19% (95% CI 6–32%). Conclusions: Our results suggest that in order to achieve optimal outcomes, children with MDS should be referred for allogeneic HSCT soon after diagnosis and that unlike in adult MDS, pre HSCT chemotherapy does not appear to improve outcomes. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Stem Cell Transplant Reverses The Phenotype Of DOCK8 Deficiency

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2114-2114
Author(s):  
Jennifer Cuellar-Rodriguez ◽  
Alexandra F Freeman ◽  
Juan Gea-Banacloche ◽  
Helen Su ◽  
Jennifer K. Grossman ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Conditioning Regimen ◽  
Organ Damage ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Post Transplant ◽  
Dock8 Deficiency

Abstract Background DOCK8 deficiency— a combined immunodeficiency characterized by recurrent sinopulmonary infections and severe cutaneous DNA viral infections, eczema, food and drug allergies, and increased risk of viral driven malignancies— results from homozygous or compound heterozygous mutations in the dedicator of cytokinesis 8 protein. Allogeneic hematopoietic stem cell transplantation (HSCT) represents a potential curative therapy for DOCK8 deficiency. Methods We treated 4 patients with DOCK8 deficiency with allogeneic HSCT using a reduced toxicity, myeloablative-conditioning regimen consisting of busulfan 3.2 mg/kg/day IV for 4 days and fludarabine 40 mg/m2/day for 4 days. Two patients received matched related donor allogeneic HSCT, and 2 received 10/10 HLA matched unrelated donor allogeneic HSCT. All patients received tacrolimus, and short methotrexate on days 1,3, 6, and 11, for graft-versus-host-disease (GVHD) prophylaxis. Indication for transplant was severe recurrent infections with end organ damage in three patients, and a refractory EBV-virus driven lymphoma at the time of unrelated donor PBSC transplant in the fourth patient. Results The ages of the patients at the time of transplant were 27, 25, 18, and 16. The median follow-up for patients was 7 months (range 5-18 months). All 4 patients engrafted at a median of 12 days, and all 4 had complete reconstitution of the CD3/CD4 and CD3/CD8 compartments with donor cells. Clinical correction of the DOCK8 clinical phenotype occurred within 3-6 months of engraftment and correlated with lymphocyte reconstitution. Mucositis was the major side effect of the transplant-conditioning regimen. All had transient worsening of their pre-transplant infections 1-3 months post-transplant. In the patient with an EBV-virus driven lymphoma that had been refractory to chemotherapy, there was complete resolution of the disease on PET scanning at 100 days post-transplant. One patient, who received unrelated donor bone marrow cells, had skin GVHD that responded to a short course of steroids. There was no chronic GVHD. Conclusions Allogeneic HSCT in DOCK8 deficiency results in reconstitution of the deficient lymphocyte compartments that are present pre-transplant and complete reversal of the infection susceptibility phenotype. There was minimal regimen-related toxicity, and the incidence of GVHD was low despite complete donor chimerism. With genetic testing for DOCK8 deficiency now more widely available, we anticipate that earlier diagnosis will enable patients to be transplanted earlier in their clinical course, before significant organ damage or the development of viral-driven malignancies Disclosures: No relevant conflicts of interest to declare.

Herpes Zoster (HZ) Infection in the Post-Hematopoietic Stem Cell Transplant Pediatric Population May Be Preceded by Transaminitis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3167-3167
Author(s):  
Jason N. Berman ◽  
Winter Berry ◽  
Molin Wang ◽  
Donna S. Neuberg ◽  
Eva C. Guinan
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Pediatric Population ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Surprising Result ◽  
Skin Involvement ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract HZ infection is a common complication following hematopoietic stem cell transplantation (HSCT). We reviewed the incidence, complications, and associated risk factors in a post-HSCT pediatric population at a single center and examined whether antecedent blood counts or transaminase levels (AST, ALT) might predict the onset of infection prior to the development of skin manifestations. Seventy-eight children between the ages of 2 months and 21 years developed HZ among the 309 patients, on whom data was available, who underwent HSCT from January 1995 to December 2002. Underlying diagnoses included: acute leukemia (n=108), chronic myelogenous leukemia (n=22), myelodysplastic syndrome (n=24) and other conditions (n=155). Two hundred patients underwent an allogeneic HSCT (98 sibling donor, 102 unrelated donor) and 109 underwent an autologous HSCT. The incidence of HZ was 25% by 10 months and 40% by 70 months post-HSCT. Post-herpetic neuralgia occurred in 21/73 (29%; 95% CI=19%, 41%) evaluable patients, disseminated skin involvement in 15/74 (20%; 95% CI= 12%, 31%) patients and visceral organ involvement in 6/75 (8%; 95% CI= 3%, 17%) patients. Acyclovir prophylaxis for cytomegalovirus (CMV) antigen positivity was given for 21 days post-BMT in 49/75 (65%) patients and had no impact on the incidence or onset of HZ, nor did immune compromise (defined as history of chemotherapy or underlying primary immune deficiency) prior to HSCT. Risk factors for development of HZ included: patient age-greater than 10 years (p&lt;0.0001), allogeneic HSCT (p&lt;0.001), and conditioning with total body irradiation (TBI) (p&lt;0.059). Type of allogeneic donor did not add significantly to the model. Graft-versus-host-disease (GVHD) increased the interval to HZ infection (p&lt;0.0018). There was insufficient evidence to attribute this surprising result to CMV prophylaxis. However, prior GVHD did increase the risk of disseminated skin involvement (p&lt;0.016). There was a significant change in ALT level in the month preceding diagnosis of HZ (p&lt;0.02), with 22/37 (59%) evaluable patients having a progressive increase. This rise in ALT level was not associated with GVHD (p=0.60). Changes in AST levels, white blood cell and platelet counts were not significant. Forty-four patients were admitted to hospital for HZ infection for a median of 6 days (range 2–39). Length of stay for allogeneic patients was significantly affected by skin dissemination and visceral involvement (p&lt;0.023 and p&lt;0.034, respectively) and not by donor type, prior immune status, GVHD or TBI. Inclusion of HZ infection post-HSCT in the differential diagnosis of patients with a rising ALT level, particularly if &gt; 10 years of age after allogeneic HSCT with TBI conditioning may allow for earlier initiation of therapy with less morbidity and decreased need for hospital admission.

Zygomycosis After Allogeneic Hematopoietic Stem Cell Transplantation: A French Multicenter Cohort Study (2003-2008)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1263-1263
Author(s):  
Alienor Xhaard ◽  
Fanny Fanternier ◽  
Eric Dannaoui ◽  
Anne Bergeron-Lafaurie ◽  
Claire Lacroix ◽  
...  
Keyword(s):  
Cohort Study ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Attributable Mortality ◽  
Cell Transplant ◽  
Line Treatment ◽  
First Line ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
First Line Treatment

Abstract Abstract 1263 Background: To evaluate the clinical characteristics and outcome of zygomycosis (ZG) in allogeneic hematopoietic stem cell transplant (HSCT) recipients. Methods: Retrospective cohort study involving HSCT patients with ZG diagnosed between 2003 and 2008, from 19 centres. During this period, 4138 allogeneic HSCT were performed in these centers. Results: ZG incidence was 0.56% (n=23). Twenty patients (87%) were male. Median age was 44 years (range: 3 to 63 years). Donors were non HLA-identical in 14 cases and conditioning regimens were reduced intensity in 8. ZG occurred a median of 217 days post transplant (range: 0 to 2693 days). Fifteen patients had active graft-versus-host disease (GVHD). Twenty patients were receiving steroids at a median dose of 1 mg/kg/day (range: 0.1 to 2 mg/kg/day) at ZG diagnosis. Ten patients (43%) had diabetes mellitus. Nine patients (39%) had experienced a previous proven or probable invasive filamentous fungal infection (Aspergillus: 8, Trichoderma:1) a median of 115 days (range: 8 to 392 days) before ZG diagnosis. ZG was a breakthrough infection in 20 cases. Before ZG diagnosis, 13 patients were on voriconazole therapy for a median duration of 61 days (range 3 to 394 days), 4 patients were on posaconazole (PCZ) for a median of 61 days (range 7 to 88 days). Other patients were receiving caspofungin, itraconazole or voriconazole. Lungs were the most common site of infection (65%); two patients had a disseminated infection. Histology was performed in 52% of the patients, and contributed to diagnosis for 83% of biopsies. Culture was positive in 83% of cases. The main causal species were Lichtheimia spp. and Rhizopus spp. Median time between the first clinical symptom and diagnosis was 8 days (range: 2 to 34 days). Twenty patients received an antifungal. All but 2 patients received a lipid formulation of amphotericin B as first-line treatment. Eleven patients received PCZ, two as first-line treatment. Surgery was performed in eight patients. Median treatment duration was 47 days (range: 2 to 730 days). Nine patients responded to treatment. Nineteen patients (83%) died a median of 46 days after ZG diagnosis (range: 0 to 1449 days). ZG attributable mortality was 79% (15/19 patients). Four patients are alive a median of 706 days after ZG diagnosis (range: 705 to 1955 days). Conclusion: ZG is a late event with a poor prognosis after allogeneic HSCT. Because ZG diagnosis is difficult, special attention must be paid to patients on long-term antifungal treatment for a previous mold infection, and with protracted GVHD. Disclosures: No relevant conflicts of interest to declare.

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