Small Populations of PNH-Type Cells in Aplastic Anemia Patients Are Derived from PIG-A Mutant Stem Cell Clones without Proliferative Advantage.

Abstract Several studies revealed that a small number of glycosylphosphatidylinositol anchored protein-deficient cells are detectable in peripheral blood of healthy individuals but these PNH-type cells do not persist for a long time because they are originated from committed progenitor cells rather than primitive stem cells with PIG-A gene mutations. We have studied more than 700 patients with AA for the presence of CD55-CD59- granulocytes and red blood cells using highly sensitive flow cytometry and detected 0.003% or more PNH-type cells in about 50% of patients. In patients whose proportions of PNH-type are very low, the appearance of PNH-type cells may also be transient because they are not derived from true PIG-A mutant stem cell clones. In an attempt to characterize hematopoietic clones from which small populations of PNH-type cells are originated, we studied changes in the proportion of PNH-type granulocytes, clinical findings, and PIG-A mutations over 3–7 years on 52 AA patients (18 males and 33 females). The initial examination revealed less than 0.1% (0–0.075%) PNH-type granulocytes in 21 patients (Group A) and more than 0.1% (0.101–36%) PNH-type granulocytes in 31 patients (Group B). In three (14%) patients of Group A, PNH-type granulocytes became undetectable 2.9, 1.3 and 1.6 years after the initial examination. 0.007 % granulocytes became detectable 2.5 years after the first examination which produced a negative result in one patient. Among the other 17 (81%) patients of Group A, proportions of PNH-type granulocytes remained stable at 0.03–0.41% over 3–6 years. By contrast, 5 (16%) patients of Group B showed an apparent increase in the proportion of PNH-type cells (from 1.46%, 1.63%, 3.31%, 23%, and 36% to 79%, 21%, 83%, 55%, and 78%, respectively) 2 to 4 years after the initial examination. Four of the five developed clinical signs of hemolysis. The proportion of PNH-type cells in Group B patients remained stable in 33 (63%) patients and declined in 12 (23%) patients. When we sorted a small (0.04%) population of PNH-type granulocytes from a patients of Group A and analyzed PIG-A gene, only one point mutation at position 479, C to T was revealed in the exon 2. The finding that the proportion of PNH-type cells remained stable over 3 years in most Group A patients suggests that very low proportions of PNH-type cells are derived from primitive hematopoietic stem cell clones with PIG-A mutation. Among AA patients displaying small populations of PNH-type cells, only those whose proportion of PNH-type cells are more than 1% may be at a high risk of developing hemolytic PNH.

Download Full-text

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

Blood ◽

10.1182/blood.v106.11.5292.5292 ◽

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.

Download Full-text

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

Blood ◽

10.1182/blood.v110.11.4875.4875 ◽

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.

Download Full-text

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

Blood ◽

10.1182/blood.v110.11.5026.5026 ◽

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.

Download Full-text

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 ◽

10.1182/blood.v116.21.4538.4538 ◽

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.

Download Full-text

The Impact of Sex Steroids Inhibiter on Thymic Function Following Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v112.11.4599.4599 ◽

2008 ◽

Vol 112 (11) ◽

pp. 4599-4599

Author(s):

Xiaodan Luo ◽

Qifa Liu ◽

Zhiping Fan ◽

Yu Zhang ◽

Juan Ning

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Acute Gvhd ◽

Control Group ◽

Hematopoietic Stem ◽

Thymic Function ◽

Significant Difference ◽

Group A ◽

Group B ◽

The Impact

Abstract Objective To evaluate the impact of luteinizing hormone-releasing hormone (LHRH) on the protection of thymic function after allogenic hematopoietic stem cell transplantation (allo-HSCT). Methods Established model of allogenic murine HSCT (C57BL/6→BALB/c). The severity of acute graft-versus-host-disease (GVHD) was assessed by a clinical scoring system that incorporates five clinical parameters: weight loss, posture, activity, fur texture and skin integrity. The intra-cellular levels of interferon-γ (INFγ), tumor necrosis factor-α (TNFα) and interleukin-1β (IL-1β) in thymocyte were analyzed by protein array and thymic function was evaluated by quantification of signaljoint TCR rearrangement excision circles (sjTRECs). Results Recipients in group A (allogenic mice), B( allogenic LHRH castrated-mice) and C (syngenic mice) all attained hematopoiesis reconstitution. White blood cell counts of mice in groups A, B and C were over 1.0×109/L on day (10.60±1.34), day (9.40±0.55) and day (9.40±0.89), respectively. There was no significant difference among the time of hematopoiesis reconstitution in three groups. The time of acute GVHD occuring was on day +11±0.5 and +14±0.5 posttransplantation, respectively, in groups A and B, and all mice had acute GVHD with the incidence of 100% in groups A and B. The average scores of acute GVHD in groups A and B were (1.56±0.51) and (0.92±0.49), respectively. Acute GVHD scores in group A was significantly higher than that in group B (P=0.000). The levels of INFγ, TNFα and IL-1β in control groups were 1.67±1.76 ng/ml, 1.69±1.07 pg/ml and 5.55±3.56 pg/ml, respectively. The levels of INFγ in groups A, B and C were (10.74±2.55) ng/ml,(6.81±2.33) ng/ml and (5.52±3.96) ng/ml, respectively. The levels of TNFα were (7.51±2.89) pg/ml, (4.30±0.63) pg/ml and (3.36±2.31) pg/ml, respectively. The levels of IL-1β were (25.83±8.91) pg/ml, (19.33±3.03) pg/ml and (11.94±4.00) pg/ml, respectively. There were significant differences in the levels of cytokines between group A and the control group (P=0.000, 0.000, 0.000). The levels of cytokines in group B were significantly higher than those of control group (P 0.010,0.037,0.000). The levels of INFγ in group C were significantly higher than those of the control group (P=0.044). Among groups A, B and C, there were significant differences in the levels of INFγ, TNFα and IL-1β (P=0.001,0.000,0.000). The levels of INFγ and TNFα in group A were significantly higher than those in group B (P=0.041,0.013). The levels of INFγ, TNFα and IL-1β in group A were significantly higher than those in group C (P=0.009, 0.002, 0.000). The analysis of linear regression showed that the average levels of INFγ paralled with aGVHD scores (r2 0.363,P=0.038). The average sjTRECs copies/1000 PBMNCs were (39.41±44.68) in the control group and (12.29±13.02), (58.01±71.82) and (19.61±14.59) in groups A, B and C, respectively. There was no significant difference in the multiple comparisons of peripheral blood levels of sjTRECs among these four groups (P=0.575). Conclusion INFγ ATNFα and IL-1β might be involved in the damage to the thymus by acute GVHD. Sex steroid inhibitor can not only reduce the severity of thymic damage after allo-HSCT, but also reduce the severity of aGVHD and the mechanism might be associated with the reduction of intracellular levels of INFγ and TNFα in thymocyte.

Download Full-text

Inefficacy of Immunosuppressive Therapy for Severe Aplastic Anemia Progressing From Non-SAA: Improved Outcome After Allogeneic Hematopoietic Stem Cell Transplantation

Frontiers in Oncology ◽

10.3389/fonc.2021.739561 ◽

2021 ◽

Vol 11 ◽

Author(s):

Limin Liu ◽

Xin Zhao ◽

Miao Miao ◽

Yanming Zhang ◽

Wenjing Jiao ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Aplastic Anemia ◽

Immunosuppressive Therapy ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem ◽

Group A ◽

Group B

Background and AimsThis study aimed at comparing the efficacy and safety of severe aplastic anemia (SAA) cases that had met the criteria for SAA at the time of diagnosis (group A) with SAA that had progressed from non-SAA (NSAA) (group B), both undergoing first-line immunosuppressive therapy (IST). Additionally, group B was compared with SAA that had progressed from NSAA and who had been treated by allogeneic hematopoietic stem cell transplantation (allo-HSCT) (group C).MethodsWe retrospectively compared 608 consecutive patients in group A (n = 232), group B (n = 229) and group C (n = 147) between June 2002 and December 2019. Six months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values, treatment-related mortality (TRM), secondary clonal disease, 5-year overall survival (OS) and failure-free survival (FFS) were indirectly compared between group A and group B, group B and group C.ResultsSix months after treatment, the rate of overall response and the fraction of patients who had achieved normal blood values in group A was higher than in group B (65.24% vs. 40.54%, P < 0.0001; 23.33% vs. 2.25%, P < 0.0001); the same was true for group C (92.50% vs. 2.25%, P < 0.0001). The rate of relapse in group B was higher than in group C (P < 0.0001), but there were no differences in TRM and secondary clonal disease (P > 0.05). There were no differences in estimated 5-year OS between groups A and B (83.8% ± 2.6% vs. 85.8% ± 2.6%, P = 0.837), or between B and C (85.8% ± 2.6% vs. 77.9% ± 3.4%, P = 0.051). The estimated 5-year FFS in groups A and C was higher than for group B (57.1% ± 3.3% vs. 39.7% ± 3.4%, P < 0.001; 76.7% ± 3.5% vs. 39.7% ± 3.4%, P < 0.0001).ConclusionThese results indicate that IST is less effective in SAA progressing from non-SAA but allo-HSCT can improve outcomes.

Download Full-text

Rabbit ATG Plus Cyclophosphamide with or without Fludarabine Is Superior Conditioning Regimen for Patients with Severe Aplastic Anemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

Blood ◽

10.1182/blood.v128.22.2212.2212 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2212-2212

Author(s):

Parvez Ahmed ◽

Tariq Mahmood Satti ◽

Qamar Un Nisa Chaudhry ◽

Kamran Mehmood ◽

Nighat Shahbaz ◽

...

Keyword(s):

Stem Cell ◽

Aplastic Anemia ◽

Conditioning Regimen ◽

Disease Free Survival ◽

Severe Aplastic Anemia ◽

Hematopoietic Stem ◽

Free Survival ◽

Group A ◽

Group 2 ◽

Group B

Abstract Objective: To compare rabbit antithymocyte globulin (ATG) containing conditioning regimen (group A) with horse antilymphocyte globulin (ALG)-based regimen (group B) for sibling allogeneic hematopoietic stem cell transplant (HSCT) outcome, disease free survival, rejection and complications in severe aplastic anemia patients. Methods: We analysed 205 aplastic anemia patients undergoing allogeneic HSCT from HLA matched sibling donors from July 2001 to April 2016. Group A (n=169) received conditioning with ATG plus Cyclophosphamide (CY) 200 mg/Kg with Fludarabine (Flu) 120mg/m2 (n=100) or without Flu (n=69), whereas group B comprised of CY plus ALG (n=36). The stem cell source was bone marrow (43.9%); PBSC (8.3%) and bone marrow plus PBSC (47.8%). Cyclosporin (CsA) was given as GVHD prophylaxis in 129 patients, while methotrexate (MTX) was added to CsA in 76 cases. Chi-square test was used to compare categorical variables. Kaplan Meier survival curves with log rank test was applied to compare the groups for survival analysis. Results: Overall survival was 78.7% in Group A compared to 69.4% in group B (p=0.23). Patients in group A had significantly better disease free survival (DFS) (75.1%) than group B (55.6%) (p=0.018). The incidence of acute GVHD was 18.3% in Group A compared to 22.2% in Group 2 (p=0.64), while chronic GVHD was significantly higher in Group 2 (22.2%) as compared to Group A (9.5%) (p= 0.04). Likewise frequency of Mucositis was high in Group B (30.5%) compared to Group A (10.7%) (p = 0.006). Moreover, patients receiving ALG-based conditioning had more frequent infections (86%) compared to ATG-based group (67.4%) (p=0.03). There was no significant difference within group A with respect to use of fludarabine as part of conditioning. Conclusion: Rabbit ATG containing conditioning regimen is associated with less complications and better survival in patients with severe aplastic anemia undergoing allogeneic HSCT. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Administration of Plerixafor in Poor Mobilizers Allows Mobilization of Haematopoietic Progenitors: Clonogenic Potential and Engraftment Analysis

Blood ◽

10.1182/blood-2019-125055 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5633-5633

Author(s):

Laura Pezzetti ◽

Giambattista Bertani ◽

Liliana Intropido ◽

Tiziana Lamacchia ◽

Mariateresa Pugliano ◽

...

Keyword(s):

Stem Cell ◽

Conflicts Of Interest ◽

Biological Data ◽

Hematopoietic Stem ◽

Group A ◽

Stromal Cell Derived Factor ◽

Semi Solid ◽

N 93 ◽

Group B ◽

Poor Mobilizers

BACKGROUND Plerixafor (PLX) blocks the binding of stromal cell-derived factor to CXCR4, resulting in hematopoietic stem cell (HSC) release from the bone marrow. It has been successfully used as a mobilizing agent in poor mobilizers (PM). The best strategy is probably the "pre-emptive" (on demand) use, as it allows an "on time" identification of PMs, preventing collection failure and need for further mobilization. Usually a cut-off of < 10/ μL CD34+ cell count at leukocyte recovery is used for PLXa dministration, while a minimum level is not defined, as mobilization may be obtained even with very low values. An important issue that has not been extensively explored so far is represented by the biological characteristics of the yields collected with PLX, especially clonogenicity, and its clinical counterpart, represented by the engraftment times observed after transplant. In this report we retrospectively analysed our data on the use of PLX in PMs, evaluated its efficacy and focused on the clonogenicity of collected stem cells and engraftment post auto transplant (ASCT). METHODS We collected data on PM patients mobilized with PLX between 2011 and 2019:Clinical data: mobilization and collection performance, transplant rate and engraftment times (days to PMN > 500/uL).Biological data: Clonogenicity of HSC collected after PLX, measured by hematopoietic progenitor semi-solid cultures according to Stem Cell Technology. These clinical and biological data were then compared to those obtained in patients mobilized without PLX and in allogeneic donors who received G-CSF in the same period. RESULTS From January 2011 to June 2019 PLX was used in 73 mobilization cycles, performed in 64 patients. Patients characteristics are described in Table 1. 105 doses of PLX were given during 73 mobilization cycles (1,44 doses/cycle) and 93 collections performed (1,27/ cycle). Circulating CD34+ pre PLX administration were in median 6,81/µl (range: 0,27-21), while after treatment 26,20/µl (range: 4,8-155,4). Using a cut-off of ≥ 10/ μL CD34+, a successful mobilization was achieved in 67/73 cycles (success rate 91,7%). Overall 59 out of 64 patients achieved the collection target (92,2%) at any time and 54/64 have been transplanted (84,4%), the other 10 not yet due to mobilization failure (n=2), insufficient yield (n=3), clinical unfitness (n=2) or because too early (n=3). A median of 4 HPC bags were reinfused (range: 2-12) and median time to WBC engraftment was 10 days (8-21). Engrafment times are in line with those of MM and NHL patients mobilized without PLX in the same period of time (median: 10, range: 8-12) at our Institution. Interestingly, 33 out of 35 pts mobilized with PLX (94,2%), compared to 442/449 (98,4%) engrafted in ≤11 days. We analyzed the cellular composition of yields and clonogenicity of HSC collected in 3 different groups:Group A: PLX mobilization (n=93)Group B: chemo + G-CSF without PLX (n=755)Group C: G-CSF mobilization in allogeneic donors (n=206) We failed to demonstrate a statistical difference between clonogenicity in group A and B (p=0,691), while clonogenicity was slightly but significantly higher in group C compared to group A and B (p< 0,001). Data are shown in tables 2,3 and 4. CONCLUSION In our cohort of patients, administration of PLX in PM resulted in successful mobilization of HPCs with good clonogenicity and engraftment potential. The use of PLX allowed an high proportion of patients to undergo ASCT. Disclosures No relevant conflicts of interest to declare.

Download Full-text

Clinical Outcome of Cerebrospinal Fluid Shunting for Communicating Hydrocephalus in Mucopolysaccharidoses I, II, and III: A Retrospective Analysis of 13 Patients

Neurosurgery ◽

10.1227/neu.0b013e3181f8c11d ◽

2010 ◽

Vol 67 (6) ◽

pp. 1476-1482 ◽

Cited By ~ 16

Author(s):

Hamidreza Aliabadi ◽

Renee Reynolds ◽

Ciaran J Powers ◽

Gerald Grant ◽

Herbert Fuchs ◽

...

Keyword(s):

Cerebrospinal Fluid ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Clinical Signs ◽

Intracerebral Hematoma ◽

Communicating Hydrocephalus ◽

Group A ◽

Cerebrospinal Fluid Shunting ◽

Group B

Abstract BACKGROUND: Intracranial pathology is a well-documented feature of mucopolysaccharidoses (MPSs), including communicating hydrocephalus (CH). Neither the success nor the complications of cerebrospinal fluid shunting in MPS patients have been well documented. OBJECTIVE: To retrospectively analyze 13 children with communicating hydrocephalus and MPS at our institution between 1998 and 2006. METHODS: Thirteen patients diagnosed with MPS I, II, or III presenting for stem cell transplantation were retrospectively analyzed. Patients underwent a rigorous pretransplantation workup, including magnetic resonance imaging of the brain. If imaging revealed ventriculomegaly, a lumbar puncture was performed. If intracranial pressure was > 20 cm H20 or the patient demonstrated clinical signs of hydrocephalus or evidence of clinical decline with increasing ventricular size on imaging, a ventriculoperitoneal shunt (VPS) was placed. Clinical outcomes were analyzed after dividing the patients into 2 groups: patients who underwent VPS before (group A) and after (Group B) stem cell transplantation. RESULTS: There were 8 patients in group A and 5 in group B. Group B patients developed more severe complications, including 2 patients who required VPS early after transplantation, one who died secondary to intracerebral hemorrhage and another who developed a subdural empyema. Of the 8 patients in group A, 5 had complications, including 2 shunt infections, a punctate intracerebral hematoma, shunt tube migration, and 3 shunt failures. CONCLUSION: This is the largest review of MPS patients with communicating hydrocephalus. It demonstrates that VPS is an effective treatment. MPS patients need to be evaluated for hydrocephalus before stem cell transplantation because pretransplantation shunting appears to have the most favorable risk/benefit ratio.

Download Full-text

Long-Term Outcome of Therapy-Related Myelodysplastic Syndromes and Acute Myeloid Leukemias Arising in Patients Treated for Lymphoma or Solid Tumors.

Blood ◽

10.1182/blood.v110.11.2464.2464 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2464-2464

Author(s):

Raffaella Milani ◽

Salvatore Palmieri ◽

Manuela Zanni ◽

Filiberto Pollio ◽

Anna Dodero ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Disease Status ◽

Low Risk ◽

Hematopoietic Stem ◽

Monosomy 7 ◽

Group A ◽

Group B

Abstract Several studies have shown that therapy-related MDS (tMDS) and AML (tAML) have a poor outcome with very few long-term survivors. Curative treatment strategies are not yet standardized and the role of hematopoietic stem cell transplantation (SCT) is still not fully elucidated in standard care treatment. We performed a retrospective outcome research with the aim of looking at the survival curves of tMDS and tAML patients treated at 7 different Institutions. According to the presence of comorbidities or a matched donor, 71 patients (pts) received the best treatment option based on attending physician opinion: 24 pts (group A) with tAML (n=13, FAB M0, M1, M2, M4) and tMDS (n=7 RAEB-2. n=4 RAEB-1) received allogeneic transplantation, 28 pts (group B) with tAML (n=20, FAB M0, M1, M2, M4, M5) and tMDS (n=3 RAEB-2, n=4 RAEB-1, n=1 RA) received chemotherapy and 19 pts (group C) received supportive care only (n=1 tAML, n=18 low-risk MDS or RAEB-1 (n=5)). Median age was 55 years (range 23–67) in group A, 61 years (range 27–73) in group B and 55 years (range 22–70) in group C. Conventional karyotype analysis was available in 12 pts of group A (n=7 complex, n=1 normal, n=2 isolated del(7q) or monosomy 7, n=1 isolated del(5q), n=1 trisomy 21) and in 15 pts of group B (n=3 complex, n=8 normal, n=1 isolated del(Y), n=1 isolated del(11), n=1 isolated trisomy 11, n=1 isolated trisomy 8). In the group A, all pts, because of age and/or comorbidities, received a fludarabine-based reduced-intensity conditioning followed by allogeneic peripheral blood SCT. Disease status at transplant was categorized as low risk (n=9 CR1 or CR2), high risk (n=3 PR, n=6 PD, n=2 refractory) and 4 pts were treated up-front. The median time from diagnosis to allografting was 6 months (range: 1–80 months). Pts received allogeneic stem cells from HLA-matched siblings (n=16), or HLA-matched unrelated donors (n=6), or haploidentical related donors (n=2). All pts engrafted. Acute GVHD grade II–IV occurred in 6 pts (n=1 post-DLIs), chronic GVHD developed in 6 pts (n=1 post-DLIs). OS at 5 years was 5.5%, the 4-year EFS was 0%, TRM at 100 days and at 1 year were 28%. No statistical differences were observed in TRM, EFS, and OS according to disease status at transplant and diagnosis of tMDS or tAML. DFS for pts in CR at transplant was 23% at 1 year. In the group B, pts received chemotherapy and 11 of them an autologous stem cell transplantation. OS at 5 years was 16%, EFS at 5 years was 10%, DFS at 1 year was 31%. TRM at 5 years was 30%. In the group C, OS was 28% at 5 years. Our data show that, in daily clinical practice, the outcome of patients receiving chemotherapy followed by allogeneic SCT is not improved compared to the patients not having a suitable donor. At the present time, considering the very low chance of cure, in therapy-related disorders the main goal for clinicians should be prevention.

Download Full-text