A Comparison of Clinical Outcomes of Non-T-Cell-Depleted (Non-TCD) Unrelated Donor Heamatopietic Stem Cell Transplantation (HSCT) and Non-TCD Haploidentical Related Donor HSCT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5140-5140
Author(s):  
Feng Chen ◽  
De Pei Wu ◽  
Aining Sun ◽  
Xiao Ma ◽  
Xiaowen Tang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Acute Gvhd ◽  
Peripheral Blood Stem Cell ◽  
Ex Vivo ◽  
Unrelated Donor ◽  
Group A ◽  
Related Donor ◽  
Group B

Abstract Unrelated donor HSCT and haploidentical related donor HSCT have been evaluated as alternative transplant options for the approximately 70% of patients without an HLA-identical sibling donor. To compare the clinical outcomes between Non-TCD unrelated donor HSCT and Non-TCD haploidentical HSCT, we studied 55 patients with high-risk or advanced leukemia who underwent Non-TCD HSCT from unrelated or haploidentical related donors from June 2001 to May 2006. Group A including 25 patients received HLA-matched unrelated donor HSCT, group B, including the other 30 patients, received HLA-haploidentical family donor HSCT. 20 recipient/donor pairs were allele matched and 5 pairs were 1–2 alleles disparity mismatched in the group A, HLA-haploidentical family donors in the group B included mother (22 cases), sibling(5 cases) and offspring (3 cases). Patients with myeloid leukemia were conditioned with the regimen consisting of Simustine (MeCCNU) 250mg/m2×1day, Ara-c 4g/ m2×2days, busulfan (Bu) 4mg/kg×3days, and cyclophosphamide (Cy)1.8g/m2×2days, patients with lymphoblastic leukemia were conditioned with the regimen consisting of MeCCNU 250mg/m2×1day, total-body irradition(TBI) 8Gy×1day, Ara-c 4g/ m2×2days, and Cy 1.8g/m2×2days. 15 patients received Non-TCD bone marrow transplantation (BMT), and 10 patients received Non-TCD peripheral blood stem cell transplantation (PBSCT) in the group A. 17 patients received G-CSF-primed bone marrow grafts that had not been depleted ex vivo of T cells, and 13 patients received G-CSF-primed bone marrow grafts plus G-CSF-mobilized peripheral blood stem cell without ex vivo T cell depletion in the group B. Prophylaxis against GVHD was performed with cyclosporine (CSP), short-term methotrexate (MTX), and mycophenolate mofetil (MMF), some patients received the combination of CSP, MTX and MMF plus antithymocyte globulin (ATG). When GVHD developed, methylprednisolone(MP) was given at first, if the response was poor, anti-CD25 monoclonal antibody was given to the patients as quickiy as possible and CSP was replaced with tacrolimus. All patients of the group A and 29 patients of the group B were engrafted successfully. Acute GVHD grades III-IVoccurred in 10 and 11 patients in the group A and B, respectively(the cumulaitive incidence 40% vs 37.9%, P>0.05). 2 patients relapsed in each group (the actuarial probilities of relapse 8% vs 6%, P>0.05). The 2-year probabilities of event-free survival(EFS) for the group A and B were (58.7±5.9)% and (42.2±2.0)%, respectively (P>0.05). 10 patients of the group A and 17 of the group B died of transplantation- related disease. The primary causes of death included severe acute GVHD and pulmonary infection. These results suggested that both Non-TCD unrelated donor HSCT and Non-TCD haploidentical related donor HSCT are effective treatments for patients with refractory or high-risk hematologic malignancies, the high transplantation related mortality due to GVHD and infection is still a major challenge.

Comparative 2-Arm Study for Acute Graft-Versus-Host Disease; Antithymocyte Globulin Is More Effective Than Mycofenolate Mofetil on Outcome of Allogeneic Peripheral Blood Stem Cell Transplantation from Mismatched Unrelated Donors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5395-5395
Author(s):  
Woo-Sung Min ◽  
Heeje Kim ◽  
Byoung-Sik Cho ◽  
Sung-Yong Kim ◽  
Ki-Sung Eom ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Antithymocyte Globulin ◽  
Acute Gvhd ◽  
Unrelated Donor ◽  
Group A ◽  
Unrelated Donors ◽  
Group B

Abstract We have experienced many HLA-mismatched unrelated donor hematopoietic stem cell transplantation (HSCT) for patients with high-risk AML. The availability of unrelated donors, who were categorized as high-risk for acute GvHD posttransplant, based on well understanding of impact of HLA allele or antigen mismatch immunobiology on various clinical outcomes, was investigated. With the use of different immunosuppression conditioning regimens, according to the patient-risk grouping, will allow stable HLA-mismatched unrelated donor HSCT to meet the needs best of the individual patient. Beginning on March 2004, 23 consecutive adult patients were enrolled in treatment protocols and follow-up was carried out through July 31, 2006. Patients with AML, age in the range between 17 and 58, who were all in 1st or 2nd complete remission, had high-risk assessment, in various performance status, received mainly total body irradiation containing conventional myeloablative transplantation. Specifically, for patients who were supposed to receive peripheral blood stem cells (PBSCs) from HLA-mismatched unrelated donors at the level of HLA antigen (N=5) or 1-2 alleles (N=7) at the HLA-A, B, Cw, and DR loci; if antithymocyte globulin (ATG;Thymoglobulin, SangStat), at a dose of 1.25 mg per kilogram of body weight per day, was given intravenously on days D-3 and D-2 followed by FK-506 from D-1 and short-term methotrexate at D+1, D+3, D+6, D+11 at a dose of 5mg/m2 intravenously, they were enrolled as group A (N=10). In contrast, if mycofenolate mofetil was started from D+21 and tapered out until D+60 instead of ATG, they were in the group B (N=13). Patients with unrelated donors were screened for HLA-A, B, and DRB1 alleles with the use of high-resolution (DNA sequencing) molecular typing method. Median age for group A, B were 36 (range, 17–58), 32 (range, 17–48), respectively. Sex ratio was similar between 2 groups. Group A received with a median CD34 dose of 4.2 (3.6–8.8) ×106/kg compared with 2.4 (1.6–5.5) ×106/kg of the group B. Median time to neutrophil (>0.5×109/kg) and platelet (>20×109/kg) regeneration was 13 vs 15 days, 14 vs 17 days in the group A and B respectively. After median follow-up of 9 months (range, 2–20) and 16 months (range, 3–29) for each group, acute GvHD was observed in 40% and 77%, respectively. However, 31% was greater than grade II acute GvHD in the group B and one of them died due to severe GvHD grade IV, despite none (0%) in the group A. Only 2 patients (29%) in the group A developed limited type chronic GvHD, but 3 patients in the group B together with 3 of extensive type (46% in total). Also, one case of graft rejection was observed in the group B (4%). The cumulative incidence of each group transplant related mortality (TRM) was 0% and 15%, respectively. The relapse rate was 0% in each group. Therefore, in our experience, in order to reduce TRM using unrelated donor PBSCs, particularly in the HLA-mismatched setting, it is required to cautiously apply ATG as a critical immunosuppression used in this group A as the benefits from reduction of GvHD/rejection.

Psychosocial and Behavioral Issues in Stem Cell Transplantation

2006 ◽  
Author(s):  
Sean Phipps
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Well Being ◽  
Unrelated Donor ◽  
Behavioral Issues ◽  
Leukemic Relapse

Stem cell transplantation (SCT) or bone marrow transplantation (BMT) has evolved from a heroic, experimental therapy of last resort to a standard therapy for many high-risk leukemias and the preferred first option after leukemic relapse (Sanders, 1997; Santos, 2000; Treleaven & Barrett, 1998; Wingard, 1997). The indications for SCT have widened to include a number of other malignant disorders, including lymphomas, solid tumors, and even brain tumors, as well as to a growing number of nonmalignant disorders (Meller & Pinkerton, 1998; Santos, 2000; Treleaven & Barrett, 1998). The growth of bone marrow registries that allow for wider use of unrelated donor transplants and developments in stem cell selection techniques that allow for haplotype transplants using mismatched family donors, including parents, have greatly increased the availability of SCT as a viable treatment option for seriously ill children (Mehta & Powles, 2000). At the same time, advances in supportive care have led to improved survival outcomes and thus to a rapidly growing number of long-term survivors of SCT (Santos, 2000; Treleaven & Barrett, 1998). Yet, despite the extraordinary medical and technical advances that have saved the lives of many children, SCT remains a high-risk medical procedure involving a prolonged and physically demanding treatment regimen that can challenge the coping capacities of patients and their families. Psychosocial research in pediatric SCT has progressed more slowly, but available studies indicate that SCT is a stressful experience that can have a negative impact on the social functioning, self-esteem, and general emotional well-being of survivors (Barrera, Pringle, Sumbler, & Saunders, 2000; McConville et al., 1990; Parsons, Barlow, Levy, Supran, & Kaplan, 1999; Phipps, Brenner, et al., 1995; Phipps & Barclay, 1996; Rodrigue, Graham-Pole, Kury, Kubar, & Hoffman, 1995; Stuber, Nader, Yasuda, Pynoos, & Cohen, 1991; Vannatta, Zeller, Noll, & Koontz, 1998). A number of studies have also focused on parental response to SCT (Barrera et al., 2000; Kronenberger et al., 1998; Manne et al., 2001, 2002; Phipps, Dunavant, Lensing, & Rai, 2004; Rodrigue et al., 1996; Streisand, Rodrigue, Houck, Graham-Pole, & Berlant, 2000). Much of the literature to date has focused on long-term outcomes in survivors, particularly neurocognitive and academic outcomes.

Bacterial, Viral and Fungal Infections in Patients after Allogeneic Stem Cell or Bone Marrow Transplantation - A Comparison between Patients with Related and Patients with HLA-Matched Non-Related Stem Cell Donors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4978-4978
Author(s):  
Christina T. Rieger ◽  
Johanna Tischer ◽  
Helmut Ostermann
Keyword(s):  
Bone Marrow ◽  
Candida Albicans ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Myeloid Leukemia ◽  
Fungal Infections ◽  
Stem Cell Source ◽  
Cell Source ◽  
Group A ◽  
Group B

Abstract Bacterial, viral and fungal pathogens frequently cause severe, life-threatening infections in immunocompromised patients after allogeneic stem cell transplantation (SCT). We investigated whether patients with related stem cell donors (group A) developed infections less frequently than patients with HLA-matched, non-related donors (group B). Fifty-nine consecutive patients treated at our transplantation unit between April 2004 and January 2005 were included into the analysis. We documented demographic and clinical characteristics at baseline, treatment, clinical course, microbiological examinations, clinical and radiological signs of infection and mortality. Of the total 59 patients analyzed, 22 received stem cells from related and 37 from HLA-matched non-related donors. Both groups were well balanced regarding age and weight. 50% of the patients in group A and 60% in group B were male. Most frequent diagnoses were acute myeloid leukemia (30 of 59 patients [50.8%]; group A: 68.2%; group B: 40.5%), multiple myeloma (15.2%), acute lymphoblastic leukemia (11.9%) and chronic myeloid leukemia (10.2%). Bone marrow was more often the stem cell source in group A (45.5%/ 10 patients) than in group B (10.8%/ 4 patients), peripheral stem cell transplantation respectively was predominant in the unrelated group (86.5%/ 32 patients) versus the family donor group (54.5%/ 12 patients), cord blood was used as unrelated stem cell source in1 patient (2.7%). Clinically documented infections occurred in 6% in group A and in 14% in group B. Pulmonary infiltrates were observed more frequently in group A (11 patients/ 50%) than in group B (16 patients/ 43.2%). The predominant findings were atypical infiltrates (total 16 patients), followed by signs of fungal (total 7 patients) and bacterial pulmonary infiltration (total 4 patients). Microbiologically documented infections were detected in all patients. The average number of pathogens was equal in both groups. Detected pathogens were HHV-6 (48 patients), coagulase-negative Staphylocci (17 patients), EBV (14 patients) and CMV (11 patients). Three fungal infections were detected by microbiological approaches in group A (2 × Candida albicans, 1 × Pitysporum ovale) compared to nine fungal infections in group B (5 × Candida albicans, 1 × Candida glabrata, 1 × Candida parapsilosis, 2 × Geotrichum capitatum). Two years after transplantation, 55.9% of patients were alive (group A: 68.2%; group B: 48.6%). Patients with AML had a two-year survival of 50% (group A: 53.3%; group B: 46.7%). In our study, we observed no clear relation between frequency of infection and donor type, yet there was a trend towards more invasive fungal infections in the unrelated group (13% group A vs. 24% group B).

The Effect of Costimulatory Moleculars on Graft-Versus-Host Disease after Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4875-4875
Author(s):  
Zhenhua Qiao ◽  
Fang Ye ◽  
Lei Zu
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Group A ◽  
Group B

Abstract Objective: To explore the effect of costimulatory molecular and CD25 expressed on peripheral CD4+ T lymphocytes on graft-versus-host disease(GVHD) after allogeneic hematopoietic stem cell transplantation(allo-HSCT). Methods: 1. The 21 patients who suffered of hematology diseases or malignant solid tumors and were underwent allo-HSCT and 10 normal individuals were enrolled in the study.2. For the sake of difference conditioning regimens we divided the 21 patients into two groups: patients undergoing non-myeloablative stem cell transplantation(NST) belonged to group A, others undergoing traditional myeloablative stem cell transplantation belonged to group B; we divided them into five groups for with GVHD or without GVHD and types of GVHD: group 1(group A with acute GVHD), group 2(group A with chronic GVHD), group 3(group B with acute GVHD), group 4(group B without GVHD), group 5(group A without GVHD).3. The levels of CD28, CD80, CD152 and CD25 expressions on peripheral CD4+ T lymphocytes were detected by three colors flow cytometry (FCM)in different time(before allo-HSCT,7days,14days,21days,30days after allo-HSCT, the time of GVHD and the time after GVHD treated).4.STR-PCR for detecting micro-satellites chimeras forming. Results: 1. All 21 patients achieved engraftment. By STR-PCR assay,12 cases formed complete chimeras(CC) and 9 cases formed mixed chimeras(MC). In group A,3 cases developed acute GVHD and 4 cases developed chronic GVHD; in group B,4 cases developed aGVHD. The incidence of GVHD and infection rates between group A and B has no difference(X2=3.711, P=0.144).2. Among these 21 cases,5 cases died:2 cases died of multiple organs function failure due to primary disease relapse,1 case died of bleeding in brain and 2 cases died of liver function failure for the sake of complicated with acute GVHD; others survive with disease free till present.3. The results of multivariate logistic regression models and Kaplan-Meier survival curves analyses showed: age, sex, infection, HLA-type, blood type, conditioning regiment and the times of absolute neutrophil counts and platelets recovering to normal, had no association with the incidence of GVHD;A multivariate COX survival function model analysis showed CD4CD152 and CD4CD25 are independent prognostic factors for GVHD(X2=13.128, P<0.0001).4. Patients with GVHD demonstrated higher CD4+CD28+ and CD4+CD80+ T cell levels than those without GVHD(P<0.01);patients with aGVHD demonstrated higher than those with cGVHD(P<0.05) and without GVHD(P<0.05); Patients with GVHD demonstrated lower CD4+CD152+ and CD4+CD25+ T cell levels than those without GVHD(P<0.01); the same result occurs between aGVHD and cGVHD and without GVHD. After effective treatment, unnormal CD4+CD28+, CD4+CD80+, CD4+CD152+ and CD4+CD25+ T cell levels recovered to the levels before transplantation. Conclusions: The incidences of GVHD between NST and traditional myeloablative stem cell transplantation had no difference. B7-CD28/CD152 costimulatory pathway plays a critical role in developing of GVHD. Peripheral CD4+CD28+, CD4+CD80+, CD4+CD152+ and CD4+CD25+ T cell levels were relative to recipient GVHD, especially CD4+CD152+ and CD4+CD25+ T cell levels. Down-grade CD4+CD28+ and CD4+CD80+ T cell levels and up-grade CD4+CD152+ and CD4+CD25+T cell levels could reduce the incidence of GVHD.

Gentuzumab Ozogamicin (GO:Mylotarg) Monotherapy for Relapsed AML after Hematopoietic Stem Cell Transplantation: from Morphological Target to Molecular Target.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5026-5026
Author(s):  
Shuichi Miyawaki ◽  
Nahoko Hatsumi ◽  
Takumi Hoshino ◽  
Toshihide Kawamura ◽  
Satoru Takada ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Immunosuppressive Agents ◽  
Durable Response ◽  
Hematopoietic Stem ◽  
Group A ◽  
Group B ◽  
Relapse Group

Abstract Background: The treatment for acute myeloid leukemia patients with relapse after stem cell transplantation is limited to dose reduction of immunosuppressive agents, donor leukocyte infusion (DLI), and a second transplantation. The prognosis of such patient is very poor if these therapies cannot be tolerated or are unsuccessful. Gentuzumab ozogamicin(GO) is an antibody targeted chemotherapy consisting of a humanized anti-CD33 monoclonal antibody linked to calicheamycin. The CD33 antigen is expressed on most AML cells and myeloid progenitor cells, but is not expressed on lymphocytes which play an important role in GVL effect. Therefore, GO can potentially eradicate AML cells without harming these lymphocytes. Patients: We retrospectively studied 9 patients with AML, who relapsed following allogeneic stem cell transplantation (SCT) and had difficulty tolerating DLI. Their donor sources included one 6/6 HLA-matched sibling bone marrow cells, four 6/6 HLA-matched unrelated bone marrow stem cells, and four 4/6 HLA-matched unrelated cord blood. The status of leukemia at SCT was 1st complete remission (CR) in one patient, 2nd CR in one patient, and active disease in seven patients. Treatment protocol: GO was administered at 6 mg/m2 for 2 doses separated by 2 weeks. Treatment was initially performed at morphological relapse but after April 2006 patients received treatment at molecular relapse. The molecular relapse was diagnosed by the quantitative expression of WT1 (Wilms tumor gene). (Blood.2003;101:1698–1704) Results: Five patients were treated at morphological relapse (group A) and four patients were treated at molecular relapse (group B). Eight received both doses of GO. The period from SCT to relapse ranged from 36 days to 193 days (median: 85 days). The period from SCT to GO administration ranged from 54 days to 229 days (median: 98 days). Seven of 9 patients achieved a remission (3/5 in group A, 4/4 in group B). Three CR patients in group A relapsed (day 48, 95, and 106, respectively). All of the patients in group A died within 447 days. (at 42 days, 131 days, 158 days, 173 days and 447 days, respectively, after GO). Two of the 4 patients in group B relapsed, one on day 300 and one on day 350. One patient died in CR from multiple organ failure following CMV infection; the fourth patient is still in CR. Three patients in group B are alive at 276 days, 410 days, and 443 days. Three patients developed infusion-related fever, one patients nausea. All patients developed grade 4 neutropenia and thrombocytopenia. Febrile neutropenia was observed in four patients. Five patients developed elevation of ALT, grade 3 in 1 patient and grade 1 in 4 patients. Three patients developed grade 1 hyperbilirubinemia. Only one patient developed reversible VOD. VOD occurred on thirteenth day after the administration of GO. The period between SCT and GO administration was 77 days. Conclusion: The administration of GO is effective in inducing remission in relapsed AML patients after SCT. The ability of GO therapy to induce durable response may possibly be enhanced by early therapeutic intervention before the onset of hematologic relapse. This approach is feasible and well tolerated with minimal toxicity. Additional studies in a large group of patients will be required to adequately assess the safety and efficacy of this approach.

Low Relapse without Excessive Transplant-Related Mortality Following Allogeneic Stem Cell Transplantation in Patients with High Risk Secondary Acute Myeloblastic Leukaemia and Myelodysplastic Syndromes, Long-Term Outcomes in a Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4308-4308
Author(s):  
Jean El-cheikh ◽  
Luca Castagna ◽  
Sabine Furst ◽  
Catherine Faucher ◽  
Benjamin Esterni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Allogenic Stem Cell Transplantation ◽  
Related Mortality

Abstract Abstract 4308 Allogenic stem cell transplantation (Allo-SCT) as a therapy for secondary acute myeloid leukaemia (sAML) and myelodisplastic syndromes (MDS) is the most powerful treatment option. However, (Allo-SCT) is also complicated by a high risk for treatment-related morbidity and mortality. We analysed retrospectively the data of 70 patients transplanted at our institution from June 1995 to december 2008, 44 patients (63%) with sAML and 26 patients (37%) with MDS was treated with (Allo-SCT); median age at diagnosis was 41 years, (15-70), and the median age of 42, 5 years (16-70) at transplantation; The conditioning regimen was myeloablative combining (cyclophosphamide and TBI) in 16 patients (23%) and 54 patients (77%) was with a reduced intensity conditioning (RIC) regimens combining fludarabine, busulfan, and antithymocyte globulin; 11 patients (16%) were infused with bone marrow (BM), 55 patients (79%) peripherical blood stem cells (PBSC), and 4 patients (5%) cord blood cells; in 49 cases (70%) donor was a HLA identical sibling and in 21 (30%) was a matched unrelated donor; 41 patients (59%) carried high risk cytogenetic features, like (7q-, 5q-, > 3 alterations), while was normal in 24 patients (34%), and in 5 patients (7%) was unknown. Disease status at transplantation was as follow: CR in 24 patients (34%), 34 patients (49%) was refractory or in progression after treatment, and 12 patients (17%) was with a stable disease. With a median follow-up of 55 months (3-150), 30 patients (43%) are alive, the overall survival OS at 2 years and 5 years was 48 % and 39% respectively, and after ten years of follow up, OS was 30%, 95%CI [17.8-50.8]. We observed also that 26 % of refractory patients and 54% of patients in CR are alive at five years of transplantation. The probability of progression after transplantation at five and ten years was 31% with 95%CI [20.-46.5]. 2 years and 5 years treatment related mortality (TRM) was 23% and 26% respectively, and no modification at ten year, 95%CI [14.3-37.3]. TRM occurred in 16 patients (23%). Cause of death was; infections in 5 patients (7%), GvHD in 3 patients (4%), GvHD and infection in 3 patients (4%), multi organ failure (MOF) in 5 patients (7%). In multivariate analysis; OS, PFS or TRM, were not influenced by donor type (HLA id sibling vs others), conditioning regimen (RIC vs MAC), and stem cell source (bone marrow vs PBSC). Allogenic stem cell transplantation can be considered as a good option for the treatment of patients with high risk sAML and MDS when compared with the remission rate at five years of the other nonallogeneic SCT therapies. Disclosures: No relevant conflicts of interest to declare.

Risk Factors for Developing Human Herpes Virus-6 Encephalitis and Clinical Significance of Antiviral Therapy In Early Phase After Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4538-4538
Author(s):  
Ayumi Numata ◽  
Masatsugu Tanaka ◽  
Takayoshi Tachibana ◽  
Yoshiaki Ishigatsubo ◽  
Atsuo Maruta ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Viral Load ◽  
Stem Cell Transplantation ◽  
Antiviral Therapy ◽  
Cell Transplantation ◽  
Hematopoietic Stem ◽  
Group A ◽  
Related Donor ◽  
Group B

Abstract Abstract 4538 Background: Human herpes virus-6 (HHV-6) encephalitis is a relatively rare complication after allogeneic hematopoietic stem cell transplantation (HSCT). However, the patients who developed HHV-6 encephalitis sometimes might be serious condition and suffer the consequences such as a disturbance of memory. We studied the viral load of HHV-6 after HSCT and evaluated risk factors of encephalitis, and assessed the clinical significance of antiviral therapy in early phase after HSCT for the prevention of HHV-6 encephalitis. Patients and methods: The viral load of HHV-6 by PCR was measured at 2, 3, and 4 weeks following HSCT for acute leukemia or myelodysplastic syndromes between April 2004 and May 2010. HHV-6 encephalitis was diagnosed with neurologic symptoms, the elevation of viral load in CSF, and abnormal MR imaging findings. Patients were divided into 2 groups based on the administration of antiviral agents (ganciclovir, valganciclovir or foscarnet) within 28 days after HSCT. Patients who had no treatment with antiviral agents until the development of HHV-6 encephalitis were defined as group A (n=96). Patients who received preemptive therapy within 28 days for the elevation of viral overload of HHV-6 or cytomegalovirus antigenemia, or other reason were defined as group B (n=34). Results: A total of 130 patients included 79 with acute myeloid leukemia (AML), 34 with acute lymphoid leukemia (ALL), and 17 with myelodysplastic syndrome (MDS).The median age was 41 years (range, 17–65). There were 66 males and 64 females. A disease risk at the time of transplant indicated a standard risk in 76 patients and a high risk in 54. Myeloablative conditioning was employed for 78 patients and reduced intensity conditioning was for 52. Bone marrow transplantation (BMT) from related donor, BMT from unrelated donor, peripheral blood stem cell transplantation from related donor, and cord blood transplantation were done for 39, 53, 12 and 26 patients, respectively. The median level of viral load at 2, 3, and 4 weeks after HSCT were 0 (range, 0–41200) (n=130), 0 (0-290000) (n=125), and 0 (0-3650) (n=114) copies/ml, respectively. Eight patients developed HHV-6 encephalitis in group A. Five of the eight patients with encephalitis had undergone UBMT and 3 had received CBT. The median age was 35 years (range, 22–59), 4 were male. Two patients had received the second HSCT for leukemia relapse. The median day from HSCT to diagnosis was 17.5 days (range, 15–26). The median of viral load was 6630 (range, 1610–22100) copies/ml at diagnosis. All patients received antiviral therapy either ganciclovir or foscarnet. Three of the 8 patients died on day 97 (sepsis), 160 (viral pneumonia), and 346 (chronic GVHD), respectively. Two of the five surviving patients have been suffering from short term memory deficit. By univariate analysis in group A, risk factors for developing HHV-6 encephalitis were unrelated donor (vs related donor: 14.8 vs 0%, p<0.01), ALL (vs AML and MDS: 19.2% vs 4.2%, p=0.03), fever338°C within 6 days after HSCT (vs fever< 38°C: 29.6 vs 0%, p<0.01), use of corticosteroid within 3 weeks after HSCT (vs no use: 45.5 vs 3.5%, p<0.01), and positive for viral load at 2 weeks after HSCT (vs negative: 27.3% vs 2.7%, p<0.01). The median time of starting preemptive antiviral therapy with either ganciclovir, valganciclovir or foscarnet in group B was day 20 (range, 11–28) after HSCT. No patients developed HHV-6 encephalitis in group B, although there was no significant difference of patient characteristics between group A and B. Conclusions: HHV-6 encephalitis occurring after HSCT is becoming a curable complication, but its sequelae such as neuropsychological disorders have a marked influence on the quality of life. Preemptive antiviral therapy for patients with risk factors and the elevation of viral load on day 14 might be a potential strategy for preventing of HHV-6 encephalitis. Disclosures: No relevant conflicts of interest to declare.

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