Autologous Stem Cell Transplantation (ABMT) for Recurrent Hodgkin’s Disease from 1990–2005: Factors Contributing to Post-Transplant Relapse.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2083-2083
Author(s):  
Brian Bolwell ◽  
Brad Pohlman ◽  
Matt Kalaycio ◽  
Steve Andresen ◽  
Elizabeth Kuczkowski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Prior Chemotherapy ◽  
Post Transplant ◽  
Peripheral Stem Cells

Abstract Long-term results of conventional therapy of Hodgkin’s disease (HD) has demonstrated the importance of long-term and ongoing follow-up given the potential for later complications after curative therapy. While many transplant series report follow-up of several years after ABMT, few report a 15-year experience from a single institution. This report examines the outcomes of 220 patients receiving high-dose chemotherapy and autologous stem cell transplant (ABMT) at The Cleveland Clinic Foundation from January 1990 through June 2005. Median age was 33 years (range, 14–70 years); median time from diagnosis to transplant was 19 months; 47% received prior radiation therapy; 82% had nodular sclerosis histologic subtype; number of courses of prior chemotherapy were: 1 (16%), 2 (66%), 3 (14%), 4 or more (4%). All patients received salvage therapy prior to transplant: 29% were in a complete remission (CR), 55% in a partial remission (PR), and 16% refractory. All patients received a chemotherapy-only preparative regimen, most commonly Bu/Cy/VP (73%), followed by CBV (17%). 78% received peripheral stem cells alone; 22% received either autologous bone marrow or a combination of bone marrow plus peripheral stem cells. At the present time 60% of patients are alive. Of the 88 patients who died, the most common cause of death is relapse (69% of deaths). Secondary malignancy occurred in 11 patients (5%); 9 of these cases were secondary AML/MDS and 5 of these patients with secondary malignancies have died. 44% of the entire cohort has relapsed, at a median of 9 months post-transplant (range, 1.4–76 months). 10-year overall survival is 47%. A multivariable analysis showed that the two significant variables that correlated with post-BMT relapse were the number of prior chemotherapies (p = 0.011), and patients treated in remission vs. those not in remission (p = 0.002). Of patients receiving 2 or more prior courses of chemotherapy, 60% have relapsed 8 years post-transplant, compared to 40% of those receiving one course of prior chemotherapy. The risk of relapse by the number of prior chemotherapy courses is shown graphically below: Figure Figure In conclusion, this very large series of ABMT for recurrent HD with long-term follow-up demonstrates the importance of timely autografting in relapsed HD patients. The optimal time to proceed with ABMT is after failing one, and only one, course of chemotherapy. Delaying transplant for unrealistic long-term salvage with other courses of traditional chemotherapy will negatively affect the outcome of subsequent ABMT.

Loss of P-Selectin Promotes the Function of Aged Hematopoietic and Leukemic Stem Cells.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1577-1577
Author(s):  
Yaoyu Chen ◽  
Sullivan Con ◽  
Yiguo Hu ◽  
Linghong Kong ◽  
Cong Peng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Stem Cell ◽  
Bone Marrow Cells ◽  
Leukemic Stem Cells ◽  
Wild Type ◽  
Post Transplant ◽  
Marrow Cells

Abstract Abstract 1577 Hematopoiesis is a tightly regulated biological process that relies upon complicated interactions between the blood cells and their microenvironment. Adhesion molecules like P-selectin are essential to hematopoiesis, and their dysregulation has been implicated in leukemogenesis. We have previously shown a role for P-selectin in chronic myeloid leukemia and demonstrated that in its absence the disease process accelerates. Recently, there has also been speculation that P-selectin may play a role in the aging hematopoietic stem cells (HSCs), as its expression in upregulated as a mouse ages. In this study, we show that the loss of P-selectin function dysregulates the balance of stem cells and progenitors and that these differences become more pronounced with age. We compared the percentages of HSCs, long-term (LT)-HSCs, short-term (ST)-HSCs, multipotent progenitors (MPPs), CMPs, GMPs and MEPs in bone marrow by flow cytometry between wild type (WT) and Selp-/- mice. An age-dependent LT-HSC expansion was observed in WT mice. However, this expansion was prevented by the loss of Selp as observed in Selp-/-mice. Further, we demonstrate that with age LT-HSCs in particular express more elevated levels of P-selectin. LT-HSCs and ST-HSC/MPPs were isolated from the bone marrow of young (2 months old) and old (15 months old) WT mice and examined P-selectin expression by FACS. A significant increase in P-selectin expression was observed in LT-HSCs of old mice, and this increase was not observed in the ST-HSC+MPP subpopulations. We also show that the loss of P-selectin gene has profound effects of stem cell function, altering the capacity of these cells to home. Despite impaired homing capacity, stem cells lacking P-selectin possess a competitive advantage over their wild type counterparts. Using a stem cell competition assay, HSCs derived from Selp-/- mice (CD45.2+) and WT control mice (CD45.2+GFP+) were mixed in 1:1 ratio and transplanted into irradiated WT recipients (CD45.1). The initial findings were potentially indicative of the ability of cells derived from GFP mice to more efficiently home and engraft. Despite this initial advantage, cells derived from Selp-/- eventually exhibited a competitive and statistically significant advantage over the cells derived from GFP mice. At 30 days post-transplant, 49.9±1.4% of the CD45.2 subpopulation was GFP+. At 86 days post-transplant, 25.7±3.3 % of the CD45.2 cells derived from the peripheral blood were GFP+. Similarly, 23.0±3.7% of the CD45.2 cells derived from the bone marrow of these mice were GFP+. Indeed, we demonstrate that recipients of P-selectin deficient bone marrow cells more efficiently repopulate the bone marrow than controls and that this advantage extends and expands in the long-term. Finally, we demonstrate that recipients of leukemic cells lacking P-selectin develop a more accelerated form of leukemia accompanied by significant increases in stem and progenitor cells. Bone marrow cells from donor WT and Selp-/- mice were infected with retrovirus expressing BCR-ABL-GFP, and irradiated WT recipients were transplanted with 2×105 of these transduced donor cells. At 14 days post-transplant, recipient mice from each of the groups were sacrificed, and bone marrow cells were harvested and analyzed by flow cytometry. Recipients of leukemic Selp-/- cells possessed 3.5-fold more LSCs than recipients of wild-type cells. There were 3.1-fold more LT-LSCs and 3.8-fold more ST-LSCs and MPPs in recipients of Selp-/- cells than WT cells. In addition, recipients of leukemic Selp-/- cells possessed significantly more CMP (16.9-fold) and MEP (4.5-fold) cells. Because P-selectin expression increases with age on LT-HSCs, we sought to determine the role that age plays in CML development and progression. Bone marrow cells derived from 15-month-old donor Selp-/- and WT mice were transduced with BCR-ABL, respectively, followed by transplantation of the transduced cells into recipient mice. All recipients of BCR-ABL transduced Selp-/- cells died by 23 days after induction of CML and had a median survival of 19 days, whereas recipients of the transduced WT cells survived significantly longer. This pro-leukemic role for cells lacking P-selectin expression is leukemic stem cell-specific rather than stromal cell-specific and supports an essential role for P-selectin on leukemic stem cells. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Long-Term Effect of Mesenchymal Stromal Cell Derived Extracellular Vesicles on the Restoration of Engraftment of Stem Cells in Radiation Exposed Mice

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5102-5102
Author(s):  
Sicheng Wen ◽  
Laura R Goldberg ◽  
Mark S Dooner ◽  
Mandy Pereira ◽  
Michael Del Tatto ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Term Effect ◽  
Post Transplantation ◽  
Post Transplant ◽  
Cell Engraftment ◽  
Long Term Effect

Abstract Extracellular vesicles (EVs) including exosomes and microvesicles, have been found to deliver both mRNA and transcriptional modulators to target cells and affect their phenotype. Vesicles derived from mesenchymal stem cells (MSC) have been shown to affect the phenotype and induce healing of many different cell types. Our recent published work has shown that pretreated irradiated murine bone marrow stem cells with human or murine MSC-EV in vitro, could significantly improve the engraftment capacity of radiation-damaged stem cells up to 9 months post-transplantation. Interestingly, the restoration of engraftment was not significantly observed within the first month of post-transplant, the predominant reversal effect occurred on later period of post-transplant from 3 months up to 9 months. This is indicating a long-term effect of MSC-EVs on reversal of radiation damage of stem cell engraftment capacity. To confirm this hypothesis, in our current study, the effect of human MSC-EVs on reversal of engraftment capacity of bone marrow stem cells post-radiation was investigated by an in vivo study. C57BL/6 mice were exposed to 500 cGy total body irradiation. MSC-EVs or vehicle were then injected intravenously 24, 48 and 72 hours after irradiation. The whole bone marrow were harvested at 6, 12, 26 and 53 weeks post EV-injection and then transplanted into 950 cGy exposed B6.SJL mice and engraftment evaluated at 1 and 3 months post-transplantation. In those transplanted mice at 6 weeks post-EV injection, there was slight increase in the restoration of engraftment rate (the percent of irradiated mice with EV/Vehicle treatment engraftment rate compared to healthy non-irradiated mice engraftment rate) in EV treated mice (17.58±2.32% compared to untreated mice (13.80±1.41%) after 1 month post-transplantation. However, for those mice transplanted at 12, 26, and 53 weeks post-EV injection, there were the significant higher restorations of engraftment rate in EV treated mice (40.48±6.03%, 33.93±3.76%, and 56.62±3.635) compared to untreated mice (12.39±1.30%, 15.14±2.21%, 36.21±3.63%) after 1 month transplantation respectively. The similar restorations of engraftment were also seen in 3 months post-transplantation. Our study also showed that there was a significant inhibition of stem cell engraftment at 53 weeks post 500cGy whole body radiation mice which was 36.21±3.63% of engraftment rate from healthy mice. Thus our data suggest that there is a long-term effect of MSC-EVs on the restoration of engraftment of stem cells in radiation-exposed mice. Disclosures No relevant conflicts of interest to declare.

scholarly journals A Monocentric Clinical Observation of Haploidientical Transplantation in 27 Patients with Acute Megakaryocytic Leukemia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Zhijie Wei ◽  
Fei Pan ◽  
Rong Yang ◽  
Shuquan Ji ◽  
Yue Guanlan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Down Syndrome ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Clinical Observation ◽  
Hematopoietic Stem ◽  
Acute Megakaryocytic Leukemia

Background Acute Megakaryocytic Leukemia (AMKL) accounts for approximately 10% of childhood AML and 1% of adult AML cases. Although AMKL with Down syndrome has a good prognosis, the prognosis for non-DS-AMKL is quite poor with a 3-years survival rate of less than 40%. At present, only allogeneic HSCT is curative. In our study, we followed 27 patients with AMKL who received a modified Bu/Cy/Mel protocol and underwent hematopoietic stem cell transplantation. The patients were then followed up with monocentric clinical observation. Methods From August 2015 to July 2020, 27 AMKL patients (14 males, 13 females, all non-Down-AMKL) with a median age of 2 years (range: 1-9 years) were continuously treated in our hospital (Hebei Yanda Lu Daopei Hospital) including 18 cases of chromosome abnormality including 3 cases of CBFA2T3/GLIS2 gene fusion (11.1%). Gene mutation included WT1(8), EVI1(5), JAK2(5): 18.51%, TET2(4), ASXL1(4), PTPN11(4): 14.81%, GATA1(2), GATA2(2): 7.4%. Bone marrow status before transplantation: 19 complete remission (CR) cases, 3 partial response (PR) cases, and 5 no response (NR) cases. There were 24 haploidentical transplants (including one patient going through 3 transplants), one transplant from a HLA-identical sibling donor and two from matched unrelated donors. Source of donor stem cells: parents in 23 cases, brothers in 2 cases, non-blood relationship in 2 cases, and none from offspring. HLA matching between the donor and recipient: 21 cases with HLA 5/10, 6 cases with ≥HLA 6/10. Haplo stem cells all came from BM+PBSC, with a median MNC input of 20.32x108/kg (10.1-26.7), CD34+ 11.68106/kg (4.05-22.44), and CD3+ 4.66x108/kg (2.11-11.29). Pre-treatment protocol: 27 patients received a modified Bu/Cy/Mel and were treated with graft-versus-host disease (GVHD) to prevent CsA+MMF+sMTX. Results During a median follow-up period of 10 months (range: 2-48 months), the 27 patients remained alive, with a median of +13 days (range: 9-21 days) to leukocyte transplantation and a median of +9 days (range: 4-38 days) to platelet transplantation. One month following transplantation, the bone marrow of all patients was 100% donor type. The overall survival (OS) rate was 63.0%, event-free survival (EFS) was 59.3%. OS was 84.2%, 33.3%, and 0% in the CR, PR, and NR groups, respectively (P<0.001). There were 7 cases of relapse and 10 deaths, among which 4 were caused by GVHD and 5 due to relapse. Incidence of acute GVHD (aGVHD) was 59.25% Grade I-IV and 18.51% Grade III-IV. Incidence of chronic GVHD (cGVHD) was 56%, with cystitis accounting for 14.81% of cases, 29.62% cytomegalovirus (CMV), 3.7% EBV, 0% thrombotic microangiopathy (TMA) and 18.51% infection. Conclusion For high-risk AMKL patients with poor long-term prognosis, the application of a modified Bu/Cy/Mel pretreatment significantly improves the efficacy of haploid transplantation without increasing pretreat-related death. For non-Down syndrome AMKL, we conclude that it is feasible to perform hematopoietic stem cell transplantation in CR status patients. Additional studies and multicenter and large-scale clinical studies with long-term follow-up are still needed to confirm these results. Disclosures No relevant conflicts of interest to declare.

High-Dose Therapy with Peripheral Blood Stem Cell Transplantation for Patients with Relapsed or Refractory Hodgkin’s Disease: A Single-Institution 20-Year Follow-up Experience.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2145-2145
Author(s):  
Kai Neben ◽  
Julia Meissner ◽  
Sascha Dietrich ◽  
Manfred Hensel ◽  
Alwin Krämer ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hodgkin's Disease ◽  
Peripheral Blood Stem Cell ◽  
Hodgkin’S Disease ◽  
High Dose ◽  
Blood Stem Cell Transplantation

Abstract Most patients with Hodgkin disease achieve durable remission with radiation therapy, combination chemotherapy, or both. However, patients who relapse after attaining complete remission with chemotherapy and those who have primary refractory disease have a poor outcome with conventional dose salvage chemoradiotherapy regimens. In the past 20 years, several clinical trials using high-dose chemotherapy (HDCT) or chemoradiotherapy with autologous stem cell transplantation have been reported, but only few of them focused on long term outcome, late toxicity and different treatment options after relapse. From March 1986 to August 2007, 107 patients with relapsed or refractory Hodgkin’s disease underwent HDCT with peripheral blood stem cell transplantation in our center. There were 64 males and 43 females with a median age of 31 years (range 17 – 63 years). For HDCT, 82 patients were treated with CBV (cyclophosphamide, etoposide, carmustine), while 20 patients received BEAM (carmustine, etoposide, cytarabine, melphalan) or other regimens (n=5). For the entire group, the probabilities of freedom from progression (FFP), overall survival (OS) and event-free survival (EFS) after HDCT were 65%, 61%, and 53% at 10 years, respectively, after a median follow-up of 12.4 years (range, 0.15 – 20.3 years). Notably, no relapse occurred later than 48 months post transplant. Cox analyses identified duration of remission (≤12 versus >12 months) as well as disease status prior to transplantation (complete remission versus partial remission versus stable / refractory disease) as significant prognostic factors for FFP, EFS, and OS. Early mortality rate (≤100 days) declined from 17.1% to 8.3% after 1992 subsequent to introduction of hematopoietic growth factors for stem cell mobilization. Late mortality rate (>100 days) was 30.8% (n=33), causes of death were Hodgkin’s disease (n=21), secondary malignancies (n=6), fibrosis of the lung (n=3), myocardial fibrosis (n=1), perforated sigmoid diverticulitis (n=1) and septicemia (n=1). The probability of secondary malignancies was 6.4% and 12.1% after 5 and 10 years, respectively. For the patients relapsing after HDCT (n=33), the median OS was 17.3% at 5 years. We found that patients with a remission time of >6 months after transplantation had a prolonged 5-year OS of 50.3% versus 0% (p=0.03) in patients with remission times of ≤6 months. To date, three of 33 patients live disease-free more than 5 years after relapse. These patients were treated with allogeneic transplantation (n=1), secondary HDCT (n=1) or conventional chemotherapy (n=1), suggesting that different treatment approaches have the potential to rescue individual patients although the overall outcome after HDCT failure is poor. In conclusion, HDCT can provide long-term disease control in patients who have failed primary therapy for Hodgkin’s disease. Although the results as a whole are encouraging for chemosensitive patients and have improved over time, new therapeutic strategies are needed to reduce toxicity of HDCT and improve the clinical outcome of those patients who relapse after HDCT.

Absence αof 4 Integrin in Hemopoietic Stem Cells Limits Their Self-Renewal Potential in Vivo.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 118-118
Author(s):  
Thalia Papayannopoulou ◽  
Gregory V. Priestley ◽  
Linda M. Scott
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Self Renewal ◽  
Post Transplant ◽  
Adult Mice ◽  
Cell Niche

Abstract We have previously shown that bone marrow (BM) cells from adult mice with conditional ablation of α4 integrin transplanted into lethally-irradiated recipients have a partial impairment in their homing and especially their short-term engraftment (MCB, 23:9349, 2003). However, the ability of α4−/− stem cells (HSC) to maintain post-transplant long-term hematopoiesis and to self renew was not tested. Therefore, we performed competitive repopulation experiments: α4+/+ cells mixed in equal proportions with α4−/− cells (verified by FACS) were given to each of 10 lethally irradiated recipients (0.5x10 6/mouse). At 30, 100, 200, and 298 days post-transplant, engraftment was evaluated in blood (PB) and BM. By d. 200, 7 of the 9 surviving mice had 81.6±3% α4+/+ cells in their PB and 97.5±0.1% in their BM. In the remaining 2 mice the proportion of α4+/+ PB cells was 35.6±12%, however by d. 298 increased (93.4±2.5% in BM). To overcome a putative partial homing defect for long-term repopulating cells, similar to the one documented using a surrogate CFU-C assay, we repeated the competitive repopulation experiment using not only 1:1, but an increased ratio of α4−/− cells to 3:1 (or 6:1 by CFU-C ratio) given in splenectomized recipients. By 12 wks α4+/+ cells among Gr1+ were 77±3.7% in PB in 10 mice with 1:1 initial transplant and 79±3.8% in 10 given 3:1 cells. These results showed that 4+/+ cells greatly outcompete the α4−/−cells and contributions by α4−/− cells are lost early and late post-transplant. Further insight was provided by transplantation of α4−/− HSC without competitor cells. 12 mice transplanted with α4−/− BM cells were sacrificed at 2 wks (6 mice), at 10 wks (3 mice) and 1 year (3 mice) later. Despite normal PB counts, evaluation of bone marrow and spleen at all times post-transplant showed subnormal values for progenitor cells vs. concurrently transplanted controls. 10 wks post-transplant 1 of the 3 mice sacrificed showed ~50% α4+/+ cells in circulation, while the other 2 had mostly α4−/− cells. From the latter (pooled BM), 2° transplants were carried out and sacrificed 14 wks later. At that time the 5 recipients had 27.5%±4.7 α4+/+ cells in their circulation. At 1 year the 3 primary transplant surviving mice had mostly α4−/− hematapoiesis and served as donors (pooled BM) for 2° transplants (n=9), evaluated 26 wks later. 5 of 9 2° recipients showed mostly α4+/+ cells, whereas 4 recipients had a mean of 6.8±1.9% α4+/+ cells in their blood. Each of these 4 recipients served as a 3° donor for 20 transplants (5/donor) which again were evaluated 25 wks later. There was a 30% survival at that time, and all 6 surviving mice were reconstituted with α4+/+ cells (multi-lineage; contributed by host and not by non-ablated donor stem cells). These data suggested that although long-term repopulation can be established with α4−/− cells in 1°recipients, hematopoiesis is quantitatively abnormal and cannot be sustained beyond a 2° transplant. Taken together, all our transplantation experiments provide compelling evidence that α4−/− HSC have a competitive disadvantage compared to +/+ cells in transplantation, and a deficit in maintaining normal hematopoiesis and stem cell self-renewal. We speculate that α4−/− HSC either are not settled to extramedullary niches supporting sustained hematopoiesis, or do not respond to signals emanating from the stem cell niche. Either way, the data underscore the requirement of α4 integrin in the interaction of HSC with the stem cell niche in order to realize their full self-renewal potential.

Abstract 239: Stem Cell Therapy Improves Critical Limb Ischemia

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Alaa Marzouk
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Embryonic Stem ◽  
Limb Ischemia ◽  
Control Group ◽  
Chronic Limb Ischemia

Introduction: The journey from single cell to complex being is attributable to stem cells role. Adult stem cells originate during ontogeny & persist in specialized niches within organs. Asymmetric division of each stem cell during differentiation produces : one daughter stem cell & one daughter transit amplifying/intermediate cell having migratory properties. Forced migration of hematopoietic stem/progenitor cells (HSPC) from bone marrow into peripheral blood is called mobilization. Accumulating evidence suggests that attenuation of the chemokine stromal derived factor-1(SDF-1)-CXCR4 axis that plays a pivotal role in retention of HSPC in bone marrow (BM) results in the release of these cells from the BM into peripheral blood. Recently, adult cells have been genetically reprogrammed to an embryonic stem cell like state. Induced pluripotent stem cells (IPSCs) were similar to human embryonic stem cells in morphology, proliferative capacity, expression of cell surface antigens, & gene expression. Treatment of ischemic vascular disease of lower limbs remains a significant challenge. Unfortunately, if medical & surgical salvage procedures fail, amputation is an unavoidable result for those patients. Aim of Work: (Hypothesis) To assess the application of implantation of autologous stem/progenitor cell in the treatment of chronic limb ischemia & to evaluate the safety, efficacy & feasibility of this novel therapeutic approach. Methods: A total of 24 patients with chronic limb ischemia not eligible for arterial reconstruction or endovascular procedures were enrolled & randomized (1:1) to either the implanted group or the control group. Control group: Conventional medical therapy in the form of anti platelet therapy & vasodilators. Implanted group: Subcutaneous injection of 300μ g/day of recombinant human granulocyte colony stimulating factor (G-CSF) for 5 days to mobilize stem/progenitor cells from BM. Total leucocytic count is measured daily to follow up successful mobilization of bone marrow mononuclear cells (BMMNCs). Stem cell Harvesting After 5 days peripheral blood mononuclear cells (PBMNCs) were harvested using a cell separator. Samples from apheresis products are subjected to TLC measurement & immunophenotypic characterization of CD34+ cells by flow cytometry. The collected PBMNCs were implanted by multiple intramuscular injections into ischemic limbs. Results: There was significant increase in pain free walking distance & ankle/brachial index (ABI) & significant decreased rest pain. Effectiveness was documented by : reduced number of amputation, increase ABI & improvement of the quality of life in therapeutic group compared to control group. Conclusion: The novel therapeutic approach of PBMNCs implantation in patients with chronic limb ischemia is safe, feasible & effective in decreasing co-morbidity & rate of amputation. Safety was manifested by absence of complications during G-CSF therapy or during harvesting & injection of the stem cells. Recommendations: 1- Future studies on larger number of patients & longer follow up. 2- Controlled studies using different methods & different cell population (PBMNCs, BMMNCs or MSCs) to compare the outcome of each. 3-Studing the role of endothelial progenitor cell dysfunction in different ischemic diseases to develop successful gene therapy.

Low mortality from lymphocyte predominant hodgkin's disease with long-term follow-up

1994 ◽  
Vol 30 ◽  
pp. 268-269
Author(s):  
Stephan Bodis ◽  
Madeleine Kraus ◽  
Geraldine Pinkus ◽  
Barbara Silver ◽  
Peter Mauch
Keyword(s):  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Long Term Follow Up

Long-Term Follow-up of Residual Mediastinal Masses in Treated Hodgkin's Disease Using MR Imaging

1996 ◽  
Vol 37 (1P1) ◽  
pp. 323-326 ◽  
Author(s):  
R. Nyman ◽  
G. Forsgren ◽  
B. Glimelius
Keyword(s):  
Mr Imaging ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Mediastinal Masses ◽  
Long Term Follow Up ◽  
Residual Masses ◽  
The Masses ◽  
Post Therapy

Purpose: Long-term follow-up of residual mediastinal masses in treated Hodgkin's disease using MR imaging. Material and Methods: Ten patients, with substantial residual mediastinal masses of low signal intensity (SI) in the T2-weighted image (T2WI), were reinvestigated with MR 19–79 months after completing treatment of Hodgkin's disease. All patients were in complete remission. Results: During the follow-up period, the masses had decreased in size by 0–95% (median 67%) as compared to their initial post-therapy size. The SI continued to be low in the T2WI and was unaffected by the degree of size reduction. Conclusion: It is speculated that these mainly fibrotic residual masses undergo slow degradation of the fibrotic part and/or resorption of remaining inflammatory tissue. It is important to understand the natural, long-term MR imaging changes of these residual masses in order more easily to recognize tumour recurrence or other pathologic conditions.

Growth factor treatment prior to low-dose total body irradiation increases donor cell engraftment after bone marrow transplantation in mice

Blood ◽  
2002 ◽  
Vol 100 (1) ◽  
pp. 312-317 ◽  
Author(s):  
Estelle J. K. Noach ◽  
Albertina Ausema ◽  
Jan H. Dillingh ◽  
Bert Dontje ◽  
Ellen Weersing ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Growth Factors ◽  
Low Dose ◽  
Donor Cell ◽  
Hematopoietic Growth Factors ◽  
Cell Engraftment ◽  
Total Body

Abstract Low-toxicity conditioning regimens prior to bone marrow transplantation (BMT) are widely explored. We developed a new protocol using hematopoietic growth factors prior to low-dose total body irradiation (TBI) in recipients of autologous transplants to establish high levels of long-term donor cell engraftment. We hypothesized that treatment of recipient mice with growth factors would selectively deplete stem cells, resulting in successful long-term donor cell engraftment after transplantation. Recipient mice were treated for 1 or 7 days with growth factors (stem cell factor [SCF] plus interleukin 11 [IL-11], SCF plus Flt-3 ligand [FL], or granulocyte colony-stimulating factor [G-CSF]) prior to low-dose TBI (4 Gy). Donor cell chimerism was measured after transplantation of congenic bone marrow cells. High levels of donor cell engraftment were observed in recipients pretreated for 7 days with SCF plus IL-11 or SCF plus FL. Although 1-day pretreatments with these cytokines initially resulted in reduced donor cell engraftment, a continuous increase in time was observed, finally resulting in highly significantly increased levels of donor cell contribution. In contrast, G-CSF treatment showed no beneficial effects on long-term engraftment. In vitro stem cell assays demonstrated the effect of cytokine treatment on stem cell numbers. Donor cell engraftment and number of remaining recipient stem cells after TBI were strongly inversely correlated, except for groups treated for 1 day with SCF plus IL-11 or SCF plus FL. We conclude that long-term donor cell engraftment can be strongly augmented by treatment of recipient mice prior to low-dose TBI with hematopoietic growth factors that act on primitive cells.

scholarly journals CD30 (Ki-1)-positive malignant lymphomas: clinical, immunophenotypic, histologic, and genetic characteristics and differences with Hodgkin's disease

Blood ◽  
1996 ◽  
Vol 87 (7) ◽  
pp. 2905-2917 ◽  
Author(s):  
DA Filippa ◽  
M Ladanyi ◽  
N Wollner ◽  
DJ Straus ◽  
JP O'Brien ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Hodgkin's Disease ◽  
Hodgkin’S Disease ◽  
Bone Marrow Involvement ◽  
Skin Lesions ◽  
Cell Phenotype ◽  
Cell Type ◽  
Null Cell

This study compares the histologic and immunophenotypic features of 71 cases of primary CD30+ diffuse large-cell lymphomas (DLCL) and 128 cases of Hodgkin's disease (HD) and discusses the clinical features of 52 patients with CD30+ DLCL. It includes analysis of sites of involvement, staging, response to treatment, sites and treatment of recurrences, and disease-free and overall survival. Diagnostic immunophenotypic differences were found between CD30+ DLCL and HD. All cases of CD30+ DLCL were positive for one or more common or lineage- specific lymphocyte antigens or for EMA. In contrast, 96.9% of HD cases were negative for CD45, CD45-RO, CD43, and CD20. The four exceptions are discussed. All cases of HD were negative for EMA. In patients with CD30+ DLCL, a T-cell phenotype was found in 60%, a null-cell type in 22%, and a B-cell type in 18% of the cases. The median age of patients with T- and null-cell phenotype was 22 years (range, 4 to 72). Fifty- two percent of them had high-stage (III and IV) disease and 61% had extranodal involvement at presentation, including 25% with skin lesions. Lymph nodes draining the skin lesions became involved in seven of 11 patients. No patient had initial bone marrow involvement. Most patients were treated with chemotherapy, and 83% had a complete remission. Fifty-four percent remain free of disease with a median follow-up of 47 months. Thirteen patients (29%) had one or more recurrences and five of them remain free of disease after salvage therapy, with a median follow-up period of 79 months. The clinical stage did not affect survival, probably as a result of different therapy. The t(2;5) translocation was found in five of 15 patients who had cytogenetic abnormalities. Of the other 10 cases, the translocation was detected by reverse transcriptase-polymerase chain reaction (RT- PCR) in four of five cases studied. All nine cases were of T- or null- cell phenotype. The cases of B-cell CD30+ DLCL had a characteristic immunophenotype. All were negative for EMA. These patients were older and had frequent bone marrow involvement but no skin infiltration by lymphoma. All three patients who were human immunodeficiency virus- positive (HIV+) had lymphomas of B-cell lineage. Detection of the t(2;5) translocation by molecular genetics is a useful and highly specific marker in the differential diagnosis between HD and CD30+ DLCL.

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