Antiviral Therapy in Patients With Hematologic Malignancies, Transplantation, and Aplastic Anemia

2009 ◽  
Vol 46 (3) ◽  
pp. 230-247 ◽  
Author(s):  
Timothy Jancel ◽  
Scott R. Penzak
Keyword(s):  
Aplastic Anemia ◽  
Antiviral Therapy ◽  
Hematologic Malignancies

scholarly journals Allogeneic marrow grafting with partially mismatched, unrelated marrow donors

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1375-1381 ◽  
Author(s):  
RD Gingrich ◽  
GD Ginder ◽  
NE Goeken ◽  
CW Howe ◽  
BC Wen ◽  
...  
Keyword(s):  
Pilot Study ◽  
Aplastic Anemia ◽  
Low Dose ◽  
Acute Gvhd ◽  
Hematologic Malignancies ◽  
Severe Aplastic Anemia ◽  
Host Disease ◽  
Granulocyte Count ◽  
Allogeneic Marrow ◽  
Acute Graft

Forty patients with advanced hematologic malignancies or severe aplastic anemia received marrow grafts from partially mismatched, unrelated marrow donors. All patients were administered conventional prophylaxis for acute graft-v-host disease (GVHD) consisting of methotrexate and low-dose glucocorticoids. All but two patients who survived at least 30 days showed durable engraftment. Six patients survive 17+ to 36+ months following transplantation. Severe acute GVHD was seen in 47% of the patients; however, no direct correlation between GVHD and the degree of mismatching could be determined. Fatal infections were seen in 29 patients, and in the majority the infection occurred after the granulocyte count had risen to greater than 500 cells/microL. We conclude that the problems encountered in this pilot study can potentially be solved, and that further studies with this type of marrow grafting are warranted.

Primary Graft Failure (GF) after Unrelated Donor Cord Blood Transplants (UCBT): Risk Factors and Management.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 44-44 ◽  
Author(s):  
Ka Wah Chan ◽  
Michael S. Grimley ◽  
Candace Taylor ◽  
Donna A. Wall
Keyword(s):  
Risk Factors ◽  
Cord Blood ◽  
Aplastic Anemia ◽  
Bone Marrow Failure ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematologic Malignancies ◽  
Viral Reactivation ◽  
Unrelated Donor ◽  
Cell Dose

Abstract Primary GF is recognized as a major risk in UCBT. Both graft (cell dose and quality of the cord blood unit) and recipient (diagnosis of aplastic anemia, prior chemotherapy exposure) characteristics have been reported as being associated with non-engraftment. Here we present a large series of UCBT patients from a single institution and analyze the risk factors and management of this complication. Between 3/2001 and 7/2006, 106 consecutive patients (pts), of median age 5.3 (range 0.1–18.4) years and weight median 22 (range 4–85) kg, received UCBT at Texas Transplant Institute. 13 did not achieve donor engraftment as documented by recovery of ANC< 500/μl by day + 42, and lack of donor cells on ≥2 RFLP analysis of the bone marrow. Failure to attain engraftment occurred in 5/27 with a non-malignant disorders, and 8/79 with hematologic malignancies (p< 033). Non-engraftment was less common in better HLA matched transplants (≥5/6 HLA match: 1/45 vs ≤ 4/6 HLA : 12/61; p< 0.02). Preliminary analysis showed no difference in cord blood TNC/kg, CD34/kg and pre thaw CFU/kg in pts who had primary GF compared to the rest of the cohort. A post thaw CFU/pre-freeze ratio of <20% was more common in primary GF. Among the 79 pts with hematologic malignancies (HM), 8 did not engraft. 4 died early; 1 from persistent leukemia, and 3 from transplant-related complications (TRM). Of the remaining 4 pts with HM, 2 were ALL children in CR1. The other primary GF occurred in 2/5 children with HLH (both with active disease at UCBT), 2/8 the children transplanted for aplastic anemia, and one pt with CD40L deficiency who had primary GF. The 9 pts who had not relapsed or died of TRM went on to second (2nd) UCBT 33 to 95 (median 55) days after first transplant (1st UCBT). Conditioning regimen for 2nd UCBT was fludarabine 175mg/m2, cyclophosphamide 50mg/kg, TBI 2 Gy, ± ATG in 7/9 patients. Median cell dose for 2nd UCBT were 3.6 × 107/kg. HLA matching was similar to 1st UCBT. There was one TRM (respiratory failure) but the rest (8/8) engrafted; with ANC >500/μl at a median of 15 (range 5–64) days, and platelets > 20000/μl at a median of 92 (range 24 to 137) days. All became transfusion-independent, and as of 8/1/2006, 7 of 9 pts are alive. All have complete donor chimerism 164–1616 (median 672) days after 2nd UDCBT. EBV-lymphoproliferatve disorders developed in 2 patients and it was fatal in one. Other viral infections encountered were BKV(1), HHV-6(1), CMV(3) in the blood; adenovirus(1) and enterovirus(1) in the stool; and BKV (1) in the urine. Acute graft-versus-host disease (GVHD) was diagnosed in 2/8 pts. 7/8 pts surviving >100 days had chronic GVHD, and it was extensive in 5 pts. It is important that primary GF be recognized as a risk of UDCBT and a back-up donor source be identified prior to transplant. Children with intact/active immune systems prior to transplant are at greater risk. Early 2nd UCBT, before patient’s condition deteriorates, is a feasible treatment alternative. This immunosuppressive preparative regimen is well tolerated early post first UCBT and can result in reliable engraftment, albeit a greater risk of chronic GVHD and viral reactivation post transplant.

Clinical Implications of Clonal Cytogenetic Abnormalities of Aquired Aplastic Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4217-4217
Author(s):  
Sung Hyun Kim ◽  
Ji Hyun Lee ◽  
Kyung A. Kwon ◽  
Suee Lee ◽  
Sung Yong Oh ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Hematologic Malignancies ◽  
Initial Diagnosis ◽  
Monosomy 7 ◽  
Cytogenetic Abnormalities ◽  
Significant Difference ◽  
Group 3 ◽  
Group 2 ◽  
Normal Cytogenetics

Abstract Abstract 4217 Background Cytogenetic abnormalities (CA) have been reported infrequently in patients with otherwise typical aplastic anemia (AA). The relevance of CA in AA to the prognosis of AA and the evolution to the hematologic malignancies is controversial. Design and Methods One hundred and twenty-nine adult AA patients from four centers located in Busan, South Korea, who had successful cytogenetics at initial diagnosis were retrospectively analyzed. Results .The median follow-up duration of the overall patients was 46.8months. The ratio of severe AA to non-severe AA was 59:41. The patients were classified into 5 groups according to the CA and progression to the hematologic malignancies. Among the patients with normal cytogenetics at initial diagnosis, 117 remained AA with normal cytogenetics (Group 1). Six patients (4.7%) had CA at initial diagnosis (Group 2). The CA showed trisomy 8 in two cases and trisomy 11, deletion of Y chromosome, t(2;9), and t(22;?) in each case. One with trisomy 11 later developed monosomy 1. None of the Group 2 evolved to acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Two patients with normal cytogenetics at initial diagnosis later developed monosomy 4, and monosomy 7, respectively, with persistent AA (Group 3). Group 3 patients were treated only with intermittent transfusion but spontaneously recovered from cytopenia and are still alive without transfusion requirement. Among the AA with normal cytogenetics at initial diagnosis, four patients (3.2%) progressed to AML or MDS; two remained normal cytogenetics (Group 4), and two patients obtained structural CA (Group 5) at follow-up, respectively. Conclusion The majority of the AA patients had normal cytogenetics at initial diagnosis. Non-severe AA patients may have CA. AA patients with CA at initial diagnosis or at follow-up are not at greater risk of evolution to the hematologic malignancies, and have no significant difference in survival. Prospective studies and more patients are needed to establish the clinical relevance of CA. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reactivation of Hepatitis B Virus Infection in Aplastic Anemia Patients Receiving Immunosuppressive Therapy

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5107-5107
Author(s):  
Hua Yin ◽  
Suli Wang ◽  
Xingyu Lu ◽  
Wenyi Shen ◽  
Ruinan Lu ◽  
...  
Keyword(s):  
Aplastic Anemia ◽  
Antiviral Therapy ◽  
Immunosuppressive Therapy ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Hbv Infection ◽  
High Rate ◽  
Hbv Reactivation ◽  
Antiviral Prophylaxis ◽  
Lamivudine Therapy

Abstract Objective: The aim of this study was to assess the risk of HBV reactivation in HBsAg-positive or negative, HBcAb-positive patients with aplastic anemia (AA) receiving immunosuppressive therapy. Methods: We analyzed clinical data of 60 AA patients with HBV infection out of 201 cases. Entecavir or lamivudine therapy was initiated if HBV reactivation was encountered, or used as antiviral prophylaxis regimen for HBsAg-positive patients. Result: Among 60 AA patients, 12 were chronically infected and 48 were previously exposed. There was no difference in clinical features in AA patients with or without HBV infection. The prevalence of non-severe AA (NSAA) progressed to severe AA (SAA) was similar in two groups (35.6% vs 42.7%, p=1.0). In NSAA group, the response rate to CsA, to ATG and CsA, and progression to SAA were similar in patients with or without HBV infection (35.7% vs 35.3%, p>0.05; 42.8% vs 58.8%, p= 1.0; 35.5% vs 42.7%, p= 0.414). In SAA group, patients with or without HBV infection responded to ATG and CsA therapy similarly (83.33% vs 59.0%, p = 0.252). HBV reactivation was occurred in all 5 HBsAg positive patients without any antiviral therapy, while no HBV reactivation happened in other 7 patients received antiviral therapy. Disease course (RR=1.012, p=0.036) and absolute reticulocyte count (RR=11.556, P=0.025) were the risk factors for HBV reactivation by univariate analysis. Logistic regression indicated that HBsAg positivity without preventive therapy was the only strong factor for HBV reactivation. Conclusion: Antiviral prophylaxis is recommended for HBsAg-positive patients with AA who will receive IST because of high rate of HBV reactivation. HBV infection has no influence on the clinic course of AA, and antiviral therapy does not affect the efficacy of IST. Disclosures No relevant conflicts of interest to declare.

scholarly journals A brief, but comprehensive, guide to clonal evolution in aplastic anemia

Hematology ◽  
2018 ◽  
Vol 2018 (1) ◽  
pp. 457-466 ◽  
Author(s):  
Daria V. Babushok
Keyword(s):  
Aplastic Anemia ◽  
Somatic Mutations ◽  
Clonal Evolution ◽  
Clinical Care ◽  
Hla Class I ◽  
The Elderly ◽  
Hematologic Malignancies ◽  
Class I ◽  
Clonal Hematopoiesis ◽  
Immune Mediated

Abstract Acquired aplastic anemia (AA) is an immune-mediated bone marrow aplasia that is strongly associated with clonal hematopoiesis upon marrow recovery. More than 70% of AA patients develop somatic mutations in their hematopoietic cells. In contrast to other conditions linked to clonal hematopoiesis, such as myelodysplastic syndrome (MDS) or clonal hematopoiesis of indeterminate potential in the elderly, the top alterations in AA are closely related to its immune pathogenesis. Nearly 40% of AA patients carry somatic mutations in the PIGA gene manifested as clonal populations of cells with the paroxysmal nocturnal hemoglobinuria phenotype, and 17% of AA patients have loss of HLA class I alleles. It is estimated that between 20% and 35% of AA patients have somatic mutations associated with hematologic malignancies, most characteristically in the ASXL1, BCOR, and BCORL1 genes. Risk factors for evolution to MDS in AA include the duration of disease, acquisition of high-risk somatic mutations, and age at AA onset. Emerging data suggest that several HLA class I alleles not only predispose to the development of AA but may also predispose to clonal evolution in AA patients. Long-term prospective studies are needed to determine the true prognostic implications of clonal hematopoiesis in AA. This article provides a brief, but comprehensive, review of our current understanding of clonal evolution in AA and concludes with 3 cases that illustrate a practical approach for integrating results of next-generation molecular studies into the clinical care of AA patients in 2018.

scholarly journals Allogeneic marrow grafting with partially mismatched, unrelated marrow donors

Blood ◽  
1988 ◽  
Vol 71 (5) ◽  
pp. 1375-1381 ◽  
Author(s):  
RD Gingrich ◽  
GD Ginder ◽  
NE Goeken ◽  
CW Howe ◽  
BC Wen ◽  
...  
Keyword(s):  
Pilot Study ◽  
Aplastic Anemia ◽  
Low Dose ◽  
Acute Gvhd ◽  
Hematologic Malignancies ◽  
Severe Aplastic Anemia ◽  
Host Disease ◽  
Granulocyte Count ◽  
Allogeneic Marrow ◽  
Acute Graft

Abstract Forty patients with advanced hematologic malignancies or severe aplastic anemia received marrow grafts from partially mismatched, unrelated marrow donors. All patients were administered conventional prophylaxis for acute graft-v-host disease (GVHD) consisting of methotrexate and low-dose glucocorticoids. All but two patients who survived at least 30 days showed durable engraftment. Six patients survive 17+ to 36+ months following transplantation. Severe acute GVHD was seen in 47% of the patients; however, no direct correlation between GVHD and the degree of mismatching could be determined. Fatal infections were seen in 29 patients, and in the majority the infection occurred after the granulocyte count had risen to greater than 500 cells/microL. We conclude that the problems encountered in this pilot study can potentially be solved, and that further studies with this type of marrow grafting are warranted.

scholarly journals Invasive Fusariosis in Patients with Hematologic Malignancies at a University Hospital

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4906-4906
Author(s):  
Vildan Ozkocaman ◽  
Fahir Ozkalemkas ◽  
Burcu Dalyan Cilo ◽  
Tugcan Alp ◽  
Tuba Ersal ◽  
...  
Keyword(s):  
Skin Biopsy ◽  
Aplastic Anemia ◽  
Median Duration ◽  
None None ◽  
Fusarium Species ◽  
Hematologic Malignancies ◽  
University Hospital ◽  
Remission Induction ◽  
Fusarium Spp ◽  
Fusarium Infection

Abstract Introduction: Fusarium species cause severe infections in patients with hematologic malignancies. The types of infection caused by Fusarium spp. in humans range from infections of nail, skin, and eye in immunocompetent host to invasive and disseminated infections in mainly immunocompromised patients. Methods: We retrospectively indentified patients with hematologic malignancy and positive cultures for Fusarium species at the University Hospital (1995-2014). Results: Thirteen cases were identified over study period. Patient demographic and underlying risk factors for fusariosis are presented in Table I. Most patients had uncontrolled hematological malignancy. All patients were neutropenic at diagnosis. Pulmonary involvement was evident in 3/13 patients (23%). Skin lesions were present in 2/13 (15%) patients. Fusariosis presented as a breakthrough infection in 8/13 (62%) of patients (Table II). Positive blood cultures were in the 6/13 (46%). Conclusions: Our study has several limitations due to its retrospective nature and its relatively small size. Fusariosis, althought uncommon, continues to have poor prognosis in neutropenic leukemic patients who present with fungemia. The optimal therapy for fusariosis remains undefined, because of its rarity and the complex clinical scenarious in patients with severe immunosupression. Table 1. Characteristics of 13 patients with fusariosis No Sex/age Underlying disease Duration of neutropenia before/after (days) Fusarium spp. Diagnosis Breakthrough infections Concomitant infections Treatment of fusarium infection Outcome of Fusarium infection 1 F/41 AML/Ri 15 /6 F. verticillioides Blood None None Amp- B Eradicated, in 23 days 2 M/19 Aplastic anemia 67/54 F. proliferatum Bronchilavage None C. kefyr, C. glabrata, P. aeruginosa Amp- B, voriconazole Eradicated, in 51 days 3 M/38 AML/RÝ 31/1 F. proliferatum Bronchi lavage Fluconazole C. albicans Amp- B, voriconazole Eradicated, in 199 days 4 M/50 ALL/RÝ 25/0 F. proliferatum Blood Fluconazole K. pneumoniae Amp- B Died 5 M/43 AML/consolidation 37/9 F. solani SC haplotype 6 Skin biopsy Fluconazole C. bovis, S. arolis Voriconazole Died 6 M/45 Relapse AML/ RÝ 37/5 F. petroliphilum Blood + tissuebiopsy Itraconazole, voriconazole VRE, S. capitis, S. maltophilia Amp- B, voriconazole Died 7 M/65 AML/ RÝ 41/0 F. andiyazi Blood Posaconazol A. baumanii Amp - B Died 8 M/63 MDS tr. AML/ RÝ None F. petroliphilum Nasalbiopsy Fluconazole HSV, C. albicans, alternans spp. Amp- B, voriconazole Died 9 M/49 Refractary MDS tr. AML/ RÝ 67/94 F. solaniss. Nasalbiopsy None S. hominis, S. saprophyticus Voriconazole Eradicatedin 68 days 10 F/53 Relapse MDS tr. AML/ RÝ 25/27 F. proliferatum Nasalbiopsy Posaconazole VRE, Klebsiella, Enterobactericea Amp- B, voriconazole Eradicated, in 84 days 11 F/49 ALL/ RÝ 23/13 F. petroliphilum Nasalbiopsy None Enterococcus, S. epidermidis, E. faecalis, MRS, BLPS Amp- B, voriconazole Died 12 M/50 HCL 65/4 F. petroliphilum Blood None None Amp- B Died 13 M/52 Relapse AML/ consolidation 34/3 F. petroliphilum Blood , skin biopsy Posaconazole C. parapsilosis, C. meningosepticum, S. capitis Echinocandine, voriconazole Eradicated , in 90 days Table 2. Patient characteristics Demographic and disease characteristics Number of patients, n=13 (%) Median age 49(19-63) Male 49,5(19-63) Female 49(41-53) Female patient 3 (23) Male patient 10(77) AML/ MDS tr. AML 9 (69) Relapse 3 Remission induction 7 Consolidation 2 Reinduction 1 ALL (remission induction) 2 (15) Hairy cell leukemia 1 (8) Aplastic anemia 1 (8) Median duration of neutropenia before diagnosis (day) 34 (15-67) Median duration of neutropenia after diagnosis (day) 6 (0-94) History of DM 0 Albümin <3.5 mg/dL All Hýgh dose corticosteroid treatment within 30 days of diagnosis 1 Breakthrough infections 8 (62) While receiving posaconazole 3 (23) While receiving voriconazole 1 (8) While receiving fluconazole 4 (31) Concominant infection Bacterial, viral, fungal=11 (85) Exitus 7 (54) Disclosures No relevant conflicts of interest to declare.

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