scholarly journals Peripheral Blood WT1 Expression Predicts Relapse in AML Patients Undergoing Allogeneic Stem Cell Transplantation

2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Michele Malagola ◽  
Cristina Skert ◽  
Giuseppina Ruggeri ◽  
Alessandro Turra ◽  
Rossella Ribolla ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Threshold Value ◽  
Relapse Risk ◽  
Before And After

To evaluate if WT1 expression may predict relapse after allo-SCT, we analyzed WT1 levels on peripheral blood (PB) and bone marrow (BM) before and after allo-SCT in 24 AML patients with WT1 overexpression at diagnosis. Five copies of WT1/ABL × 104from PB were identified as the threshold value that correlated with relapse after allo-SCT. The same correlation was not identified when WT1 expression was assessed from bone marrow (BM). Eight out of 11 (73%) patients with a pre-allo-SCT PB-WT1 ≥ 5 and 4/13 (31%) patients with a pre-allo-SCT PB-WT1 < 5 relapsed, respectively (P= 0.04). The incidence of relapse was higher in patients with PB-WT1 ≥ 5 measured after allo-SCT, at the 3rd (56% versus 38%;P= 0.43) and at the 6th month (71% versus 20%;P= 0.03). Patients with pretransplant PB-WT1 < 5 had significantly better 2-year OS and LFS than patients with a PB-WT1 ≥ 5 (81% versus 0% and 63% versus 20%) (P= 0.02). Our data suggest the usefulness of WT1 monitoring from PB to predict the relapse in allotransplanted AML patients and to modulate the intensity of conditioning and/or the posttransplant immunosuppression in an attempt to reduce the posttransplant relapse risk.

Multiple Myeloma Patients Treated with Allogeneic Stem Cell Transplantation Show an Increased Frequency of Bone Marrow-Residing CD4+Foxp3+ T Regulatory Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5206-5206
Author(s):  
Djordje Atanackovic ◽  
Yanran Cao ◽  
Christiane Faltz ◽  
Katrin Bartels ◽  
Christine Wolschke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
T Regulatory Cells ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Regulatory Cells

Abstract BACKGROUND: Immunosuppressive CD4+Foxp3+ T regulatory cells (Treg) play a vital role in immune regulation. Thus, Treg contribute to the prevention of autoimmune disease and graft-versus-host reactions following allogeneic stem cell transplantation (alloSCT) but also to the inhibition of effective anti-tumor T cell responses. It has previously been suggested that the frequency of Treg is increased in the peripheral blood of patients with multiple myeloma (MM). However, little is known about the presence of Treg in the bone marrow and it is unclear whether allogeneic stem cell transplantation might deplete Treg from this immune compartment. METHODS: In the present study, we analyzed percentages of CD4+Foxp3+ Treg as well as Treg expression of CD45RA and CCR7 in the bone marrow (BM) and in the peripheral blood of MM patients who had received alloSCT (N=42), in newly diagnosed MM patients (N=18), and in healthy controls (N=15) using flow cytometry. In addition, we performed inhibition assays in order to test the functional relevance of peripheral and BM-residing Treg. RESULTS: While newly diagnosed MM patients and healthy controls showed no significant difference in the proportions of CD4+Foxp3+ Treg in the bone marrow, percentages of BM-residing CD4+Foxp3+ T regulatory cells were markedly higher (p<0.001 and p<0.01) in patients post alloSCT (3.3±0.3%) than in normal BM (1.0±0.3%) or in BM of untreated MM patients (1.8±0.4%). In both groups of patients (p<0.05) as well as in the healthy controls (p<0.001) percentages of Treg were higher in the peripheral blood than in the bone marrow. While there were no differences regarding the percentages of peripheral Treg between the remaining groups, patients post alloSCT had higher percentages of peripheral Treg than newly diagnosed patients (5.6±0.8 vs. 3.2±0.7%, p<0.05). More than 90% of these donor-derived peripheral and BM-residing Treg expressed a memory T cell phenotype, being negative for CD45RA and CCR7. Importantly, peripheral as well as BM-residing Treg of patients post alloSCT were capable of inhibiting the proliferation of autologous non-Treg CD4+ T cells. CONCLUSION: Our study demonstrates for the first time an increased frequency of immunosuppressive Treg in the bone marrow of MM patients. Remarkably, in our patients these memory-type Treg were all donor-derived and led to an efficient replenishment of Treg in the periphery. These Treg might be necessary for the prevention of graft-versus-host disease in the transplanted MM patients, however, they might also contribute to the failure of an effective graft-versus-myeloma effect in the majority of the patients.

A Characteristic Cytokine/Chemokine Milieu Is Present in the Bone Marrow Environment of Multiple Myeloma Patients Before and After Allogeneic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2795-2795
Author(s):  
Yanran Cao ◽  
Tim Luetkens ◽  
Sebastian Kobold ◽  
York Hildebrandt ◽  
Maja Gordic ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cell Lines ◽  
Allogeneic Stem Cell Transplantation ◽  
Myeloma Cell ◽  
Luminex Technology ◽  
Before And After

Abstract Abstract 2795 Poster Board II-771 Background: The interaction of Multiple Myeloma (MM) with its bone marrow (BM) microenvironment is important for the homing, survival, and proliferation of the malignant plasma cells. In this study, we aimed at answering the question which cytokines, chemokines, and growth factors are typically found in the BM of untreated MM patients as well as in MM patients after allogeneic stem cell transplantation (alloSCT) and might be involved in the pathogenesis of MM and/or Graft-versus-Host Disease (GvHD). Design and Methods: Applying Multiplex Bead-based Luminex technology and Quantikine ELISAs, we determined the concentrations of 34 cytokines/chemokines in the supernatants of 10 myeloma cell lines as well as in the plasma derived from BM and peripheral blood (PB) samples of 10 newly diagnosed MM patients, 20 MM patients post alloSCT, and 20 healthy donors. Results: Besides factors known to be secreted by myeloma cell lines (IL-1RA, IL-8, MCP-1, MIP-1α, MIP1β, MIP-3α) we observed secretion of other cytokines/chemokines such as EGF, HGF, IL2R, IL-12p40/p70, IL-22, IP-10, MIG, and RANTES. In the BM plasma samples of MM patients, we detected elevated levels of HGF, IL-2R, IL-16, EGF, IL-1RA, IP-10, MCP-1, and MIG (p<0.01 or p<0.05). Most of these factors were significantly increased in the BM compared to PB. In addition to increased levels of the factors mentioned above, the BM plasma of MM patients post alloSCT showed selectively elevated concentrations of IL-4, IL-6, IL-8, IL-12p40/p70, and eotaxin (p<0.01 or p<0.05). Eotaxin levels were particularly high in patients with chronic GvHD. Correlating the BM cytokine/chemokine levels with the clinical characteristics of MM patients, we observed that BM levels of IL-16 (r=0.829, p=0.003) and HGF (r=0.805, p=0.005) correlated positively with myeloma cell infiltration within the BM. In addition, IP-10 (r=0.770, p=0.009), HGF (r=0.645, p=0.044), and IL-6 (r=0.664, p=0.036) correlated significantly with the initial stage of disease. Conclusions: Our study demonstrates that myeloma cells themselves generate a significantly higher number of cytokines/chemokines than previously described. We show that characteristic cytokine/chemokine patterns exact in the BM environment of MM patients before and after alloSCT. Certain factors, such as MIP-1α, MCP-1, HGF, IL-16, IP-10, and eotaxin might not only be developed into diagnostic instruments and/or predictive biomarkers, but might also represent potential targets for future myeloma- or GvHD-specific therapies. Disclosures: No relevant conflicts of interest to declare.

The Outcome of Allogeneic Stem Cell Transplantation in Chronic Lymphocytic Leukaemia: A Single Centre 10-Year-Experience

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4515-4515
Author(s):  
Patrycja Zielinska ◽  
Malgorzata Krawczyk-Kulis ◽  
Miroslaw Markiewicz ◽  
Monika Dzierzak-Mietla ◽  
Anna Koclega ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Conflicts Of Interest ◽  
Cumulative Probability

Abstract Abstract 4515 Chronic lymphocytic leukemia (CLL) is an incurable disease when treated with standard chemotherapy. The only possibility to provide cure is allogeneic stem cell transplantation (allo-SCT). CLL patients aged less than 55 account for about 15% of patients and these cases allo-SCT should be taken into consideration. The indications for allo-SCT are as follows: del17p, resistance to chemoimmunotherapy, Richter’s syndrome or recurrent disease. A retrospective analysis of allo-SCT in 18 patients (10 males, 8 females) with CLL transplanted in years 2000–2010 was performed. The aim of the study was to assess of long term follow-up outcome of allo-SCT in CLL patients. The median age at diagnosis was 41ys (range: 35–51). The sibling donor was available in 16 cases (2 pts were mismatched), unrelated donors were in 2 cases (1 mismatched). Most of the pts (16 out of 18) were MRD positive when allotransplanted. Median lymphocytosis preceeding allo-SCT was 5.9G/l. Peripheral blood was the source of stem cells in 9 cases (50%), and bone marrow in the remaining 9 cases, 2 pts were transplanted with stem cells from bone marrow and peripheral blood. 4 pts (22%) underwent the allograft procedure twice or more. Reduced intensity conditioning with alemtuzumab was performed in 9 pts (50%), myeloablative regimen in 4 cases and RIC with rituximab in one case.The median number of CD34+cellsx10^6/kg was 4.1 (range: 0.86–9.64). All but one patient engrafted (this pt was transplanted again successfully in one year time). Acute graft-versus host disease (GvHD) was noted in 46% of pts (only in 2 pts grade IV). Extensive GvHD was observed only in 2 pts. Donor lymphocyte infusion (DLI) was performed in 8 pts (44%). With a median follow-up of 73 months (range: 9–89) for surviving patients, the five-year Kaplan-Meier of overall survival (OS) and progression free survival (PFS) was 55,5% and 34%, respectively. At five years, the cumulative probability of non-relapse mortality was 15%. Allogeneic stem cell transplantation remains the effective treatment in CLL for selected group of patients. Disclosures: No relevant conflicts of interest to declare.

The Comparison of Immune Components in Three Grafts for Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5485-5485
Author(s):  
Qian Fan ◽  
Hui Liu ◽  
Can Liu ◽  
Yiwen Ling ◽  
Min Dai ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Peripheral Blood ◽  
Research Funding ◽  
Morbidity And Mortality ◽  
Before And After ◽  
Membrane Bound ◽  
Lower Morbidity

Abstract Background Recently, a few data showed that Granulocyte-colony-stimulating factor (G-CSF) modified bone marrow (G-BM) grafts leaded a lower morbidity and mortality of graft-versus-host disease(GVHD), compared with G-CSF mobilized peripheral blood stem cells (G-PBSCs) and steady state bone marrow (SS-BM) grafts. However, the mechanism of this difference is not fully understood. In this study, we compared the immune components in the three grafts. Methods Twenty patients undergoing HLA-matched sibling donor stem cell transplantation(SCT) were enrolled in this study. Patients were randomized to receive G-BM (n=10) or G-PBSCs (n=10) transplantation. Immune components, including Human leucocyte antigen-G (HLA-G), Myeloid-derived suppressor cells (MDSCs) and T cell subsets, were detected in bone marrow (BM) and peripheral blood (PB) of donors before and at day 5 after G-CSF mobilization. Results Among 20 patients, 2 patients developed acute GVHD (aGVHD) and 5 developed chronic GVHD (cGVHD) in G-PBSCs group, and no patients developed aGVHD and only 1 developed limited cGVHD in G-BM group. For the grafts, the proportion of MDSCs in PB and BM was 1.47% ± 0.12% and 2.26% ± 0.35% (P=0.001), respectively, before mobilization. After 5 days of G-CSF mobilization, the proportion of MDSCs in PB and BM increased to be 2.73% ± 0.68% and 2.56% ± 0.12%, respectively. The increase is significant both in PB and BM (P=0.000,P=0.002, respectively), while no significant difference was found between the proportion of MDSCs in G-PB and G-BM graftes (P=0.115). The levels of HLA-G (both soluble and membrane bound) in PB and BM all increased significantly after G-CSF mobilization (all P<0.05). And the levels of HLA-G (both soluble and membrane bound) in BM were all higher than that in PB, including before and after G-CSF mobilization (all P<0.05). The total numbers of CD3+ cells were similar in BM before and after mobilization, both significantly lower than that in PB (both P<0.001). However, the lowered CD4+ cells and increased CD8+ cells in G-BM leaded to a significantly lower CD4:CD8 ratio than that in SS-BM and G-PB (both P<0.001). Conclusions The differences of immune components in the grafts might play a part in the different morbidity and mortality of GVHD. The higher expression of HLA-G in the grafts might be the main reason for the lower morbidity and mortality of GVHD in G-CSF-primed bone marrow transplantation. Disclosures: Liu: It was supported by 863 Program (No. 2011AA020105), National Public Health Grand Research Foundation (Grant No. 201202017).: Research Funding; It was supported by National Natural Science Foundation of China (Grant No.81000231, No.81270647) and Science and Technology Program of Guangzhou of China (11A72121174).: Research Funding.

Clinical Outcomes and the Impact of Anti-Thymocyte Globulin (ATG) and Chronic Graft Versus Host Disease (cGVHD) Following Pediatric Allogeneic Stem Cell Transplantation: A Comparison between Peripheral Blood and Bone Marrow as a Source of Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1809-1809
Author(s):  
Parneet Cheema ◽  
Sunil Desai ◽  
Ronald Anderson ◽  
Max Coppes ◽  
Victor A. Lewis
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Peripheral Blood ◽  
Allogeneic Bone ◽  
The Impact

Abstract INTRODUCTION: The use of peripheral blood as a source of stem cells for pediatric allogeneic stem cell transplantation remains controversial. We present a retrospective analysis evaluating the safety and efficacy of allogeneic peripheral blood stem cell transplantation (PBSCT) compared to allogeneic bone marrow transplantation (BMT) for the treatment of acute leukemia at our centre. The impact of ATG added to the treatment regimen was also evaluated in this analysis. METHODS: A chart review was conducted on all pediatric patients who underwent an allogeneic stem cell transplant for acute leukemia between April 1991 and August 2003 at the Alberta Children’s Hospital. All patients who received stem cells from HLA matched or one-antigen mismatched donors were included in this analysis. Data were analyzed using SPSS. RESULTS: 85 children (ages 9 months to 17 years) met study criteria. 24 patients underwent a PBSCT while 61 patients, a BMT for the treatment of either ALL (n=54) or AML/MDS (n=31). Median follow up time was 5.9 years. Six of 24 patients in the PBSCT group, and 30 of the 61 patients in the BMT group received ATG (p=.042). There was a trend towards increased overall survival (OS) at 5 years following PBSCT (p=.078). Disease free survival (DFS) at 5 years following PBSCT and BMT was similar (p=.297). Subgroup analysis found no difference in OS or DFS between PBSCT and BMT in patients receiving (p=.221, p=.820) or not receiving ATG as part of the conditioning regimen (p=.448, p=.820). Chronic GVHD was increased following PBSCT (45.8%) compared to BMT (19.7%) (p=.015). The rate of severe cGVHD, however, was not significantly different (25% vs. 11.5% for PBSCT and BMT, p=.119) between the two groups. No patients receiving ATG prior to PBSCT developed cGVHD (p=.009). Addition of ATG to the transplant regimen had no impact on the rate of cGVHD following BMT (p=.221). There was no increase in mortality due to cGVHD following PBSCT (p=.243) or BMT (p=.865). Although, there was a trend to improved DFS in patients who developed cGVHD following PBSCT, this was not statistically significant (p=.057). Despite a statistically significant increase in TRM found in all patients with cGVHD at one year post-transplantation (p=.048), there was no difference in TRM between the PBSCT (4.2%) and BMT (14.8%) groups (p=.173). CONCLUSION: Allogeneic PBSCT is a safe and effective alternative to allogeneic BMT for the treatment of acute leukemia in the pediatric population. Although there is an increased rate of cGVHD following PBSCT this does not appear to influence OS, DFS or TRM in our analysis. Addition of ATG into the transplant regimen decreases the occurrence of cGVHD after PBSCT. Studies to further assess the role of ATG in PBSCT are warranted.

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