Combination Chemotherapy Leading In Advanced MDS Patients to a Rapid Clearence of Bone Marrow Blasts Prior Stem Cell transplantation (SCT) Is Superior to up-Front SCT Even with Intensified Conditioning for Long-Term Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4020-4020
Author(s):  
Jaroslav Cermak ◽  
Antonin Vitek ◽  
Marketa Markova ◽  
Petr Cetkovsky
Keyword(s):  
Bone Marrow ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Survival ◽  
Combination Chemotherapy ◽  
Significant Difference ◽  
Group A ◽  
Group B

Abstract Abstract 4020 A retrospective analysis of influence of different clinical and laboratory parameters on disease outcome was performed in a cohort of 43 patients with advanced myelodysplasia (MDS)(RAEB > 10% blasts + RAEB-T according to the FAB classification) who underwent allogeneic stem cell transplantation (SCT) in our institute within past 20 years; 21 patients were transplanted with < 10% of bone marrow (BM) blasts after 1 or 2 courses of induction followed by 1 or 2 courses of consolidation chemotherapy (Group A), 22 patients were transplanted with > 10% BM blasts either prior treated with combination chemotherapy or transplanted up-front with intensified conditioning (Group B). Median survival of all transplanted patients was 35,5 months (+/− 53,9 months) with a significant difference between Group A and B (57,5+/−62,3 months v.s. 18,0 +/−36,7 months, p=0.017). Estimated 3 year and 10 year survival for all patients were 53,5% and 41,9%, respectively. Estimated 3 and 10 year survival also significantly differed between Group A and B (71,4% and 57,1% for Group A and 36,4% and 27,3% for Group B). Complete remission (CR) rate was 44,2%, 18,6% patients relapsed (14,3% in Group A and 22,7% in Group B). No difference in overall survival was observed between patients with > 10% BM blasts transplanted either after chemotherapy or up-front (median survival: 26,8+/− 41,4 v.s. 18,0+/−33,8 months, respectively, p=0.65). Univariate analysis using Kaplan-Meier curves and log-rank2 test revealed as significant variables affecting overall survival: achievement of CR (p=0.007), achievement of < 10% BM blasts prior SCT (p=0.011), SCT performed < 4 months after diagnosis (p=0.031) and absence of relapse (p=0.046). Independent variables for determining overall survival (identified by Cox regression multivariate analysis) were: SCT performed < 4 months after dg. (p=0.003,χ2= 8,798), achievement of CR (p=0.011,χ2= 6,457), and age < 50 years (p=0.044,χ2= 4,053). None independent variable determining occurrence of relapse was found. Neither the percentage of BM blasts at the time of dg. and initial transfusion dependency, nor the donor origin (related or unrelated) and number of consolidation courses affected survival. Conclusions: combination chemotherapy leading to a rapid clearance of BM blasts below 10% followed by immediate SCT represented the best treatment option for younger patients with MDS with > 10% BM blasts. Patients transplanted with > 10% BM blasts at the time of conditioning had significantly inferior outcome either transplanted after previous chemotherapy or up-front with intensified conditioning. In this subset of patients, a possible benefit of addition of hypomethylating agents to the treatment schedules prior SCT should be studied. The study was supported by scientific programme MZCR 00023736. Disclosures: No relevant conflicts of interest to declare.

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.

Immunocytochemistry of the ocular surface after different techniques of limbal stem cell transplantation for chronic chemical burns

2020 ◽  
pp. bjophthalmol-2020-317051
Author(s):  
Ritu Arora ◽  
Ravindra Saran ◽  
Vikas Jha ◽  
Nikhil Dattatraya Gotmare ◽  
Parul Jain
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cytokeratin 19 ◽  
Chemical Burns ◽  
Significant Difference ◽  
Group A ◽  
Limbal Stem Cell Transplantation ◽  
Limbal Stem Cell ◽  
Group B

AimTo compare the immunocytochemistry (ICC) on impression cytology of corneal surface epithelium after simple limbal epithelial transplantation (SLET) and conjunctival-limbal autograft (CLAU).MethodsA prospective study of 20 patients above 1 year of age with chronic chemical burns, who underwent limbal stem cell transplantation (LSCT). They were divided equally in group A (SLET) and group B (CLAU). ICC was done for cytokeratin 3 (CK3) and cytokeratin 19 (CK19), preoperatively and postoperatively at 6 months.ResultsFour cases were excluded due to inadequate cellularity in preoperative or postoperative samples. On ICC analysis, in the remaining 16 patients mean CK3 and CK19 positivity changed from 2.06%±1.73% and 83.56%±8.69% preoperatively to 70.62%±13.2% (p<0.0001) and 5.93%±4.17% (p<0.0001), respectively, at 6 months post LSCT. In group A (8 patients) mean CK3 and CK19 positivity of 2%±1.8% and 84.5%±8.4% preoperatively changed to 70%±13.8% (p<0.0001) and 6.25%±5.1% (p<0.0001) at 6 months respectively. While in group B (8 patients), it was 2.12%±1.7% and 82.62%±9.4% preoperatively and 71.25%±013.5% (p<0.0001) and 5.62%±3.2% (p<0.0001) at 6 months. There was no significant difference in expression of CK3 (p=0.084) and CK19 (p=0.744) post SLET or CLAU.Three patients with complete reversion had clear corneas at 6 months.ConclusionReversion of the epithelium to corneal phenotype was documented post LSCT with no difference in expression of CK3 between the two procedures (SLET/CLAU).

The Efficacy and Safety of Recombinant Human Thrombopoietin in Patients with Hematological Malgnancies After Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4565-4565
Author(s):  
Miao Miao ◽  
Wu Depei ◽  
Aining Sun ◽  
Ying Wang ◽  
Lingzhi Yan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Platelet Transfusion ◽  
Severe Thrombocytopenia ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Group A ◽  
Group B ◽  
Recombinant Human Thrombopoietin

Abstract Abstract 4565 OBJECTIVE: To evaluate the efficacy and sefety of recombinant human thrombopoietin(rhTPO) prior to engraftment in adults with hematological malignancie who received allogeneic haematopoietil stem cell transplantation(Allo-HSCT). METHODS: This sutdy was a randomized, controlled clinical trial,38 patients were hematological malignancie, inclulding acute and chrinic myeloid leukemia, acute lymphoblastic leukemia, lymphoma.They received Allo-HSCT and were randomly divided into groups(group A 19 cases, group B 19 cases).The group A was no-rhTPO as control, the group B were received rhTPO 15000U/d from +1 day, and continued until the untransfused platelet count was >70×109/L for two consecutived days. Patients received platelete transfusion when they developed severe thrombocytopenia<20×109/L. Efficacy and sefety of rhTPO on the outcome of Allo-HSCT were evaluated. RESULTS: In both group A and B, platelet decrease after Allo-HSCT had no sognificant difference. The platelet engraftment duration of group A and B was 15.68±1.36(range 11–31) days and 13.47±0.72(range 9–21) days, respectively. The amount of platelet transfusion of group A and B was 4±0.55(range 20–130) units and 2.89±0.36(range 0–50) units, respectively. The effects of rhTPO on neutrophil engraftment, hepatic function, renal function, alloergic reations and acute GVHD were not found. CONCLUSION: The platelet engraftment duration of group B was shorter than that of group A(t=27.2, p<0.001), the amount of need platelet transfusion was significently less than those in the group A.There was a statistically significant difference in platelet engraftment and platelet transfusion needed(t=2.523, p<0.05). Administration of rhTPO prior to platelet engraftment after Allo-HSCT seem to be efficacy and safe. Disclosures: No relevant conflicts of interest to declare.

scholarly journals No difference in survival after HLA mismatched versus HLA matched allogeneic stem cell transplantation in Ewing sarcoma patients with advanced disease

2021 ◽  
Author(s):  
U. Thiel ◽  
S. J. Schober ◽  
A. Ranft ◽  
H. Gassmann ◽  
S. Jabar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Ewing Sarcoma ◽  
Chronic Gvhd ◽  
Risk Stratum ◽  
Group A ◽  
Status Number ◽  
Group B

AbstractPatients with advanced Ewing sarcoma (AES) carry a poor prognosis. Retrospectively, we analyzed 66 AES patients treated with allogeneic stem cell transplantation (allo-SCT) receiving HLA-mismatched (group A, n = 39) versus HLA-matched grafts (group B, n = 27). Median age at diagnosis was 13 years, and 15 years (range 3–49 years) at allo-SCT. The two groups did not differ statistically in distribution of gender, age, remission status/number of relapses at allo-SCT, or risk stratum. 9/39 (23%) group A versus 2/27 (7%) group B patients developed severe acute graft versus host disease (GvHD). Of patients alive at day 100, 7/34 (21%) group A versus 9/19 (47%) group B patients had developed chronic GvHD. In group A, 33/39 (85%) versus 20/27 (74%) group B patients died of disease and 1/39 (3%) versus 1/27 (4%) patients died of complications, respectively. Altogether 12/66 (18%) patients survived in CR. Median EFS 24 months after allo-SCT was 20% in both groups, median OS was 27% (group A) versus 17% (group B), respectively. There was no difference in EFS and OS in AES patients transplanted with HLA-mismatched versus HLA-matched graft in univariate and multivariate analyses. In this analysis, CR at allo-SCT is a condition for survival (p < 0.02).

Subclinical Alterations in Coagulation in Patients during Conditioning Regimen before Allogeneic Hematopoietic Stem Cell Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5292-5292
Author(s):  
Qian Jiang ◽  
Xiao Jun Huang ◽  
Kaiyan Liu ◽  
Huan Chen ◽  
Yuhong Chen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Hematopoietic Stem ◽  
Blood Samples ◽  
Group A ◽  
Group B ◽  
D Dimer

Abstract Objective To evaluate the alterations in coagulation in patients during modified busulfan plus cyclophosphamide (BUCY) ± antithymocyte globulin (ATG) before allogeneic hematopoietic stem cell transplantation (allo-HSCT), and to assess the effect of ATG on coagulation system as part of conditioning regimen. Methods Thirty-five patients with various hematological malignancies undergoing allo-HSCT were assessed. Nineteen patients from HLA-identical siblings (group A) were conditioned with modified BUCY regimen, included cytarabine (2g/m2 i.v., day -9), busulfan (4mg/kg p.o. in divided doses daily, day -8 to day -6), cyclophosphamide (1.8g/m2 i.v., day -5 and day -4) and Me-CCNU (250mg/ m2 p.o., day -3). Sixteen patients from HLA-mismatched family members or HLA-matched unreleated donors (group B) were conditioned with modified BUCY + ATG regimen, added cytarabine (4g/m2 i.v., day -10 and -9) and rabbit ATG (2.5mg/kg i.v., day -5 to day -2, SangStat S.A.S., France). Blood samples were obtained before the start of regimen until day +1 after allo-HSCT. The following laboratory parameters were measured: prothrombin time (PT), active partial thromboplastin time (APTT), Fgrinogen (Fg), antithrombin (AT), D-Dimer, Fgrin degradation product (FDP), platelet (PLT), liver enzymes and bilirubin. VIII:C, IX:C, XI:C and XII:C in some blood samples with prolonged APTT were determined. Clinical hemorrhagic symptoms were monitored. Results From day -5 of conditioning regimens, temporary lengthening of APTT, which peaked on day -3, occurred in 16/19 (84.2%) patients in group A and 19/19 (100%) patients in group B, continued rise in Fg occurred in 17/19 (89.5%) patients in group A and 19/19 (100%) patients in group B, a progressive decrease of PLT was observed in all patients of two groups. Alterations of Fg and PLT were more significant in group B compared to those in group A. Transient D-Dimer increase was detected only in group B on day -3. Among intrinsic pathway coagulation factors, XII:C and XI:C were decreased commonly and significantly when APTT was prolonged. No difference between the two groups could be found with regard to PT, FDP, AT and liver parameters which remained nearly in normal ranges. Most of patients in two groups did not have overt bleeding manifestations. Conclusions Modified BUCY ± ATG conditioning regimen can induce subclinical alterations in coagulation. The regimen contained ATG has more significant effect on coagulation parameters.

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.

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.

Bortezomib Is Highly Effective For Pure Red Cell Aplasia After ABO-Incompatible Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5495-5495
Author(s):  
Fatima Khan ◽  
Michael A. Linden ◽  
Nicole D. Zantek ◽  
Gregory M Vercellotti
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Plasma Cells ◽  
Pure Red Cell Aplasia ◽  
Red Cell ◽  
Hematopoietic Stem ◽  
Red Cell Aplasia ◽  
Group A

Introduction Pure red cell aplasia (PRCA) is an uncommon complication of ABO-incompatible hematopoietic stem cell transplantation. It is characterized by anemia, reticulocytopenia and absence of erythroid precursors in a morphologically normal-appearing bone marrow. Most cases of PRCA resolve spontaneously within weeks to months. A small subset of patients has a protracted disease course requiring continued red blood cell (RBC) transfusions. There is no approved standard of care for PRCA. Tapering of immunosuppressives such as steroids and calcineurin inhibitors, plasma exchange, rituximab, and anti-thymocyte globulin have all been employed with varying success rates. We report a case of PRCA after ABO-incompatible transplant that responded remarkably to treatment with bortezomib. Case Presentation A 60 year old female received a non-myeloablative HLA-matched ABO-mismatched sibling donor transplant for lenalidomide-refractory myelodysplastic syndrome (5q-). She received fludarabine/busulfan conditioning and tacrolimus/methotrexate for GVHD prophylaxis. The donor was blood type A Rh-positive and the recipient was O Rh-positive. The patient's post-transplant course was complicated by delayed engraftment, thrombocytopenia and autoimmune hemolytic anemia. When seen at our institution 22 months post-transplant, she had transfusion-dependent anemia requiring RBC transfusions every 2-3 weeks and reticulocytopenia. Bone marrow biopsy showed erythroid aplasia and preserved hematopoiesis in other cell lines, dysplasia was absent and parvovirus testing was negative. The patient had evidence of complete engraftment based on short tandem repeat analysis. Blood typing reflected transfused type O Rh-negative RBCs. Neither A cells from the donor nor Rh-positive cells from the patient were detected. High titers of anti-A and anti-B isohemagglutinins were detected despite transfusion with washed RBCs to reduce passive transfer. She was treated with prednisone 60mg/day, rituximab 375 mg/m2 weekly x4 and methylprednisolone 1g weekly x6 without response. Eventually, all immunosuppressive medications were discontinued to induce a graft versus recipient response. Two subsequent bone marrow biopsies continued to show nearly absent erythropoiesis, and the rare erythroid cells present lacked the blood group A antigen. Since PRCA was thought to be due to the recipient's plasma cells making anti-A antibodies, bortezomib, a potent inducer of apoptosis in plasma cells, was initiated. Subcutaneous bortezomib 1.3 mg/m2 was administered weekly x4. The patient responded well to therapy. A month after completion of bortezomib, the patient's hemoglobin measured 12.1 g/dL, reticulocyte count was 174 x109/L and IgM and IgG anti-A titers were both < 1. Bone marrow biopsy showed relative erythroid hyperplasia, and the majority of the erythroid precursors expressed blood group A. The patient continues to do well and at the time of her most recent evaluation, her hemoglobin was 13.9 g/dL. She has also remained transfusion-independent. Discussion PRCA after major ABO-incompatible transplant is thought to be caused by persistence of recipient plasma cells that continue to secrete anti-donor isohemagglutinins. Antibody titers may remain elevated for a longer duration in patients receiving non-myeloablative preparatory regimens. Bortezomib is a proteasome inhibitor that selectively induces apoptosis in plasma cells. Bortezomib has been used successfully to treat anti-body mediated rejection in both renal and liver transplant patients. A case of PRCA following ABO-mismatched hematopoietic transplant that was successfully treated with IV bortezomib has also been reported. To our knowledge, this is the first reported case of isohemagglutinin-mediated PRCA after ABO-mismatched transplant that responded favorably to subcutaneous bortezomib. Limitation The lack of long-term follow-up data precludes any assessment about the durability and persistence of response to bortezomib. Conclusion Bortezomib is an effective treatment for patients with PRCA mediated by residual host isohemeagglutinins after ABO-incompatible hematopoietic transplantation. Disclosures: Off Label Use: Our presentation describes the use of bortezomib for treatment of pure red cell aplasia after ABO-incompatible hematopoeitic stem cell transplantation. Vercellotti:Sangart Inc.: Research Funding; Seattle Genetics, Inc.: Research Funding.

scholarly journals Pre-engraftment clinically significant CMV infection after allogeneic hematopoietic stem cell transplantation and its impact on engraftment

2021 ◽  
Author(s):  
Marcia Garnica ◽  
Sylvia Dalcolmo ◽  
Bianca Gaio ◽  
Andreia Almeida ◽  
Juliana Rivello ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Clinical Importance ◽  
Close Monitoring ◽  
Hematopoietic Stem ◽  
Significant Difference ◽  
Clinically Significant ◽  
Few Data

Abstract Pre-engraftment cytomegalovirus infection (CMVi) is a challenge in patients receiving allogeneic stem cell transplantation (Allo-HCT), as few data have been reported on its clinical importance. This study describes the clinical outcomes of pre-engraftment CMVi and compares them with those of episodes developing after engraftment in HCT patients. We performed a retrospective study of patients who underwent Allo-HCT from 2016 to 2020, including 111 recipients monitored by real-time PCR assay. Clinically significant CMVi (csCMVi) was documented in 81 (73%) patients. There were 29 (26%) cases of pre-engraftment csCMVi. No significant difference was observed regarding virological features, but patients with pre-engraftment csCMVi had a delayed start in treatment (24 vs. 12 days, p < 0.001) compared with those with postengraftment events. Pre-engraftment csCMVi was associated with a delay in engraftment (20 vs. 16 days, p = 0.02) and worse overall survival (54% vs. 73% 1-year OS; p = 0.020) than postengraftment events. In conclusion, pre-engraftment csCMVi occurred in 26% of our patients and was associated with engraftment delay and worse overall survival. Close monitoring of CMV DNAemia is necessary to identify these patients earlier. Prospective studies, including patients with letermovir prophylaxis, are necessary to define the standard in the management and care of this population.

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