scholarly journals Association of mannose-binding lectin levels and invasive fungal disease in hematologic malignancy patients receiving myelosuppressive chemotherapy or allogeneic hematopoietic stem cell transplantation

2016 ◽  
Vol 51 (9) ◽  
pp. 1228-1232 ◽  
Author(s):  
M M Riwes ◽  
H Leather ◽  
D Neal ◽  
C Bennett ◽  
M Sugrue ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematologic Malignancy ◽  
Invasive Fungal Disease ◽  
Hematopoietic Stem ◽  
Myelosuppressive Chemotherapy ◽  
Mannose Binding ◽  
Binding Lectin

Mannose-Binding Lectin Status Is Associated with Risk of Major Infection Following Myeloablative Sibling Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2928-2928
Author(s):  
Charles G. Mullighan ◽  
Susan E. Heatley ◽  
Silke Danner ◽  
Melinda Dean ◽  
Kathleen V. Doherty ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem ◽  
Major Infection ◽  
Mannose Binding ◽  
Conditioning Regimens ◽  
Binding Lectin ◽  
Mbl2 Genotype

Abstract Infection is a leading cause of morbidity following allogeneic hematopoietic stem cell transplantation (allo-HCT). In a previous retrospective study of related, HLA-matched myeloablative transplants, we identified associations between common inherited polymorphisms in the MBL2 gene encoding the mediator of innate immunity, mannose-binding lectin (MBL), and risk of major infection. Missense mutations resulting in low circulating MBL levels were associated with increased infection, and high-producing promoter haplotypes were protective. However, subsequent studies have been conflicting, there are no data examining non-myeloablative transplants, and the relationship between MBL2 genotype and serum MBL levels peri-transplant has not been studied. This is important as MBL is an acute phase reactant primarily synthesized by the liver, and many conditioning regimens are hepatotoxic. Here we report a prospective study examining MBL2 genotype, MBL levels and risk of major infection following HLA-matched sibling myeloablative and non-myeloablative allo-HCT. Data is available for 138 transplants, 81 myeloablative and 57 non-myeloablative. 49 of the myeloablative transplants utilized total body irradiation (TBI) based conditioning regimens. Five promoter and missense MBL2 polymorphisms were genotyped, and plasma MBL mannan-binding and C4-deposition levels were measured pretransplant for donor and recipient, and at days 0, 14 and 28 post-transplant. Major infection was defined as invasive or systemic episodes of microbiologically confirmed sepsis. MBL levels were higher in recipients than donors at baseline (t test P<0.0001), reflecting an acute phase response induced by disease and prior treatment. Recipient MBL levels increased during the peritransplant period (ANOVA P=0.0002), most strikingly in individuals without MBL2 coding mutations undergoing TBI. 59 of 138 (42.8%) recipients experienced at least one episode of major infection (myeloablative 38/81, 46.9%, non-myeloablative 21/57 (36.8%), P=NS). The most significant clinical risk factor for infection was the use of myeloablative TBI (HR 2.8, CI 1.39–5.8, p=0.004). Analyzing all transplants, MBL2 genotype (recipient P=0.07, donor p=0.08), and recipient mannan-binding MBL levels (P=0.10) were weak risk factors for infection, however the association was highly dependent upon the type and intensity of conditioning. No association was observed in non-myeloablative transplants, but a significant interaction was observed between recipient MBL2 coding mutations and the use of TBI in myeloablative transplants (Cox P=0.002). For example, 70.6% of recipients with a coding MBL2 mutation receiving TBI developed major sepsis, compared with 20% of those without mutations not receiving TBI. Our results confirm the association of MBL status with risk of infection risk post allo-HCT. Importantly, the association is restricted to myeloablative, TBI-conditioned transplants. Further studies examining the role of MBL replacement in this setting are warranted.

scholarly journals Disseminated adenovirus infection in a patient with a hematologic malignancy: a case report and literature review

2019 ◽  
Vol 5 (8) ◽  
pp. FSO412 ◽  
Author(s):  
Akane Takamatsu ◽  
Yasuaki Tagashira ◽  
Shinya Hasegawa ◽  
Hitoshi Honda
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Wide Spectrum ◽  
Hematologic Malignancy ◽  
Cord Blood Transplantation ◽  
Adenovirus Infection ◽  
Hematopoietic Stem

Human adenoviruses cause a wide spectrum of illnesses, including invasive infections, in immunocompromised hosts. We report a case of disseminated adenovirus infection following unrelated cord–blood transplantation in a 46-year-old male with a lymphoma. A review of the literature on disseminated adenovirus infections in adult patients with hematopoietic stem cell transplantation has also been included. Despite antiviral therapy, the mortality rate in hematopoietic stem cell transplantation recipients with a disseminated adenovirus infection is as high as 72%, and estimating the risk of human adenovirus infection in a timely manner is crucial to improving outcomes.

Secondary Malignancies after Hematopoietic Stem Cell Transplantation in Patients Treated with Total Body Irradiation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2741-2741 ◽  
Author(s):  
Cristina de la Fuente ◽  
Maria I. Berrocal ◽  
J. Rafael Cabrera ◽  
Carlos A. Regueiro ◽  
Rafael Fores ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Solid Tumor ◽  
Hematologic Malignancy ◽  
Secondary Malignancy ◽  
Hematopoietic Stem

Abstract We have analyzed the incidence and risk factors of developing a secondary malignancy after total body irradiation (TBI) and hematopoietic stem cell transplantation (HSCT). From March 1986 to December 2002, 205 patients received TBI as a part of the HSCT conditioning regimen. TBI was administered in 6 fractions, twice a day, up to a total dose of 12 Gy, with a median dose rate of 11.44 cGy/min. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) was performed in 119 patients and the other 86 patients received an autologous hematopoietic stem cell transplantation (AHSCT). Median age was 30 years (5–63). We have calculated the cumulative incidence of solid tumors and secondary hematologic malignancies among these patients. Death due to noncancerous causes and patients lost to follow-up were entered as a competitive risk. With a median follow-up of 32 months (0.2–229)- including patients deceased in the first three months- 13 (6.3%) developed a secondary malignancy, 7 of them (3.4%) developed a solid tumor and 6 (2.9%) developed a secondary hematologic malignancy. The 7 patients who developed a solid tumor-1 glioblastoma, 2 head and neck carcinoma, 2 basocelular carcinoma, 1 osteosarcoma and 1 cervical intraepithelial neoplasia- had received an allo-HSCT. The 6 patients that developed a secondary hematologic malignancy- 5 therapy-related leukemia/myelodisplasia (t-AML/MDS) and 1 B cell non Hodgkin’s lymphoma- had received an AHSCT. The overall probability of developing a secondary malignancy after HSCT is 2.5% at 3 years (95% confidence interval (CI) 1.1– 6); 5% at 10 years (95% CI 2.6–9.3), and 9% at 15 years (95% CI 5–16.5). The probability of developing a solid tumor after HSCT is 0.5% at 3 years (95% CI 0.1–3.6), 1.8 % at 10 years (95% CI 0.6–5.5), and 6 % at 15 years (95% CI 2.6–13.7) and the probability of developing a secondary hematologic malignancy is 2 % at 3 years (95% CI 0.8–5.3), and 3,1 % at 10 and 15 years (95% CI 1.4–6.9). Median time to develop a solid tumor was 134 months (29–229). Median time to develop a secondary hematologic malignancy was 31 (3–60) months. Multivariate analysis proved that allo-HSCT was the only risk factor of developing a solid tumor, and that AHSCT and advanced age were risk factors of developing secondary hematologic malignancy (mean age 30 vs. 50 years ). To conclude, the probability of developing a solid tumor after HSCT is higher if an allo-HSCT has been performed and increases with time. AHSCT and advanced age are risk factors for the development of a secondary hematologic malignancy, a risk that decreases 5 years after AHSCT.

Safety and Efficacy of Cytotoxic Chemotherapy after Allogeneic Hematopoietic Stem Cell Transplantation for Relapsed Hematologic Malignancy.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5333-5333
Author(s):  
Nancy M. Hardy ◽  
Jeanne Odom ◽  
Kelly Snow ◽  
Robert Dean ◽  
Steven Pavletic ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematologic Malignancy ◽  
Cytotoxic Chemotherapy ◽  
Cytotoxic Therapy ◽  
Hematopoietic Stem ◽  
Cmv Reactivation

Abstract Relapse of hematologic malignancy is a major problem after allogeneic hematopoietic stem cell transplantation (alloHSCT), with limited treatment options of proven benefit other than donor lymphocyte infusions (DLI). Additionally, toxicity from treatment with cytotoxic chemotherapy after alloHSCT may differ from conventional treatments, and could include graft-versus-host disease, allograft failure, or increased risk of infection. We retrospectively reviewed treatment outcomes of 25 patients who received cytotoxic chemotherapy as treatment for relapsed hematologic malignancies after reduced-intensity, matched-sibling donor alloHSCT. Combination therapies included: EPOCH+/− rituximab (n=12 patients); “7&3” AML induction (ida/ara-c) (n=2); FLAG (n=2); asparaginase/6-MP/vincristine (n=1); R-ICE (n=1); MIME (n=1); BVP (n=1); and bortezomib/doxorubicin/dexamethasone (n=1). Single-agent therapies included: bortezomib (n=6); gemcitabine (n=4), vinorelbine (n=3); vincristine (n=1); methotrexate (n=1); and intrathecal methotrexate and/or cytarabine (n=5). A total of 133 cycles or doses were administered, of which 20 were supported with donor stem cell boosts, and another 9 were followed by nonmobilized DLI. There were 52 Grade 3 or higher toxicity episodes recorded, most commonly: neutropenia (10 episodes); infection with neutropenia (5 episodes); thrombocytopenia (6 episodes); and anemia (3 episodes). There were 12 episodes of CMV reactivation in 8 of 15 patients at risk, including 2 cases of pneumonitis and 1 case of colitis. GVHD flares were considered definitely chemotherapy-induced (2), possibly chemotherapy-induced (7), and unlikely chemotherapy-induced (2). Unusual events after treatment included culture-negative sepsis-like illness after bortezomib (n=2), secondary (11q23) AML of donor origin after one cycle of EPOCH (n=1) and diffuse alveolar hemorrhage after EPOCH (n=1). Seven patients achieved CR with therapy for post-transplant relapse, including three durable remissions. Four patients achieved PR and seven achieved disease stabilization. Median survival after starting cytotoxic therapy was 263 days. Timing of relapse appeared to be associated with survival, with median overall survival of 95 days for patients requiring therapy before Day 100 vs. 508 days for patients after Day 100 (p=0.0008). Treatment of relapse with cytotoxic chemotherapy after alloSCT is feasible and can result in durable remissions in a minority of patients. However, administration of cytotoxic therapy after alloHSCT requires monitoring and support for hematologic toxicities, GVHD and CMV reactivation; selected patients may benefit from prophylactic stem cell boosts or immune suppression. Survival after Cytotoxic Therapy for Relapse after alloHSCT Survival after Cytotoxic Therapy for Relapse after alloHSCT

Daily performance status-based target physical activity of early rehabilitation for hematologic malignancy patients after allogeneic hematopoietic stem cell transplantation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e17020-e17020
Author(s):  
Junichiro Inoue ◽  
Rei Ono ◽  
Atsuo Okamura ◽  
Naomi Kiyota ◽  
Daisuke Makiura ◽  
...  
Keyword(s):  
Physical Activity ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Hematologic Malignancy ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Hematopoietic Stem

e17020 Background: For hematologic malignancy patients receiving allogeneic hematopoietic stem cell transplantation (allo-SCT), the maintenance and/or increase of physical activity (PA) after allo-SCT possibly lead to favorable outcomes. However, it remains to be clarified how much intensity of daily rehabilitation should be prescribed. The aim of this study was to evaluate target PA according to daily performance status (PS) in these patients. Methods: Twenty-seven allo-SCT patients were enrolled in this study (13 males, 14 females, the median age; 47 years). Written informed consent was obtained from all patients. Donor types were bone marrow (n = 12), peripheral blood stem cell (n = 6), and single-unit cord blood (n = 9). All patients received our established exercise program supervised by physical therapists just after neutrophil engraftment in a bioclean room. As an alternative value of PA, daily steps (DS) were measured by using a uniaxial pedometer (Lifecorder EX, Suzuken Co. Ltd., Nagoya, Japan), and Eastern Cooperative Oncology Group PS after allo-SCT were also assessed daily for each individual. The data were statistically analyzed by using ANOVA and Scheff 's tests. Results: A correlation between DS and PS was observed. After the early physical intervention, the mean DS of patients with PS 1, 2, or 3 in a bioclean room were 2,411 ± 1,068, 1,205 ± 572, and 597 ± 216 steps/day, respectively. DS significantly declined by about 50% according to one grade deterioration of PS. Conclusions: As the target PA correlated with PS seems to be existence, we should plan daily activity in a bioclean room to keep more than above-mentioned mean DS according to daily PS for allo-SCT patients.

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