scholarly journals Autologous Transplantation for Older Adults with AML

Cancers ◽  
2018 ◽  
Vol 10 (9) ◽  
pp. 340 ◽  
Author(s):  
Beatrice Mueller ◽  
Katja Seipel ◽  
Ulrike Bacher ◽  
Thomas Pabst
Keyword(s):  
Autologous Transplantation ◽  
Allogeneic Transplantation ◽  
Induction Treatment ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Consolidation Treatment ◽  
Autologous Hct

While the majority of patients with acute myeloid leukemia (AML) are above the age of 65 years at diagnosis, the outcome of older AML patients remains disappointing. Even if standard intensive chemotherapy induces morphologic complete remission (CR1), relapses in older AML patients are common leading to poor long-term survival outcomes. Since autologous hematopoietic stem cell transplantation (HCT) offers distinct anti-leukemic effectiveness while avoiding graft-versus-host disease associated with allogeneic transplantation, it represents an option for consolidation treatment in selected older AML patients. However, prospective studies in older AML patients assessing the benefit of autologous HCT compared to chemotherapy consolidation or allogeneic transplantation are lacking. Consequently, clinicians face the dilemma that there is considerable ambiguity on the most appropriate consolidation treatment for older AML patients in CR1. This review highlights the possible role of autologous HCT for consolidation in older AML patients reaching CR1 after induction treatment.

scholarly journals The Role of HLA in Cord Blood Transplantation

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Catherine Stavropoulos-Giokas ◽  
Amalia Dinou ◽  
Andreas Papassavas
Keyword(s):  
Cord Blood ◽  
Cord Blood Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Blood Transplantation ◽  
Survival Studies ◽  
Hla Mismatches

In recent years, umbilical cord blood (CB), a rich source of hematopoietic stem cells (HSC), has been used successfully as an alternative HSC source to treat a variety of hematologic, immunologic, genetic, and oncologic disorders. CB has several advantages, including prompt availability of the transplant, decrease of graft versus host disease (GVHD) and better long-term immune recovery, resulting in a similar long-term survival. Studies have shown that some degree of HLA mismatches is acceptable. This review is intended to outline the main aspects of HLA matching in different settings (related, pediatric, adult, or double-unit HSCT), its effect on transplantation outcome and the role of HLA in donor selection.

scholarly journals A Case of Myeloproliferative Neoplasm with BCR-FGFR1 Rearrangement: Favorable Outcome after Haploidentical Allogeneic Transplantation

2018 ◽  
Vol 2018 ◽  
pp. 1-4 ◽  
Author(s):  
Paola Villafuerte-Gutiérrez ◽  
Montserrat López Rubio ◽  
Pilar Herrera ◽  
Eva Arranz
Keyword(s):  
Kinase Inhibitors ◽  
Fusion Gene ◽  
Myeloproliferative Neoplasms ◽  
Therapeutic Option ◽  
Myeloproliferative Neoplasm ◽  
Allogeneic Transplantation ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Health Organization

Hematopoietic myeloproliferative neoplasms with FGFR1 rearrangement result in the 8p11 myeloproliferative syndrome that in the current Word Health Organization classification is designated as “myeloid and lymphoid neoplasm with FGFR1 abnormalities.” We report the case of a 66-year-old man who had clinical features that resembled chronic myeloid leukaemia (CML), but bone marrow cytogenetic and fluorescent in situ hybridization (FISH) studies showed t(8;22)(p11;q11) and BCR-FGFR1 fusion gene. He was initially managed with hydroxyurea, and given the aggressive nature of this disease, four months later, the patient underwent an allogeneic hematopoietic stem-cell transplantation (HSCT) from an HLA-haploidentical relative. Currently, HSCT may be the only therapeutic option for long-term survival at least until more efficacious tyrosine kinase inhibitors (TKIs) become available.

Allogeneic Hematopoietic Stem Cell Transplantation Cures CLL: A Retrospective Analysis from the SFGM-TC Registry.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2991-2991
Author(s):  
Mauricette Michallet ◽  
Quoc-Hung Lê ◽  
Jean-Paul Vernant ◽  
Franck E. Nicolini ◽  
Jean-Luc Harousseau ◽  
...  
Keyword(s):  
Autologous Transplantation ◽  
Disease Status ◽  
Allogeneic Transplantation ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Cord Blood Cell ◽  
The Status ◽  
The Impact ◽  
Long Term Survivors

Abstract This retrospective study concerned 471 B-CLL patients registered in the SFGM-TC registry from Apr 1,984 to Feb 2,005, who underwent either autologous transplantation (n=313, 138 F and 175 M, median age = 54, 236 PBSC and 77 BM) or allogeneic transplantation (n=158, 78 F and 80 M, median age = 49, 76 PBSC, 81 BM and 1 cord blood cell transplant from 17 related and 141 unrelated donors). Among alloT patients, 50 were ABO incompatible and 70 sex-mismatched. The median interval diagnosis-transplantation was 32 months for autoT and 51 months for alloT. Just before conditioning 302 autoT and 143 alloT were evaluated for the disease status: 100 and 26 patients were in CR, 170 and 55 were in PR, 4 and 13 in stable disease (SD), 28 and 49 in progressive disease (PD) for autoT and alloT respectively. Among alloT patients, 73 received reduced intensity conditioning (RIC) and 85 standard conditioning (72 Cyt+TBI, 33 Fluda+TBI, 23 Fluda+Bu+ATG, 8 Cyt+Bu and 21 other). Before autoT the conditioning consisted of 224 Cyt+TBI, 45 BEAM and 44 other. After alloT, 71 patients developed an aGVHD ≥ grade II and 60 developed a cGVHD (25 limited and 35 extensive). The non-relapse mortality at 1 year was 29%. With a mean follow-up of 28 months for autoT and 40 months for alloT, the probabilities of 3-year, 5-year and 8-year overall survival were 80%, 66%, 45.5% after autoT and 52%, 48% and 35% after alloT respectively. An analysis aimed to determine the percentage of long-term survivors, or patients censored on the final plateau of survival curves was performed on alloT and autoT groups. A mixture model, gfcure with Splus statistical package determined the percentages of long-term survivors and its adequacy was verified graphically. The percentage of long-term survivors for the autoT group was 1.2%, with a mean survival length for uncured population of 160 months. Fig A shows that both curves were close and consequently shows good adequacy and the absence of a final plateau. The percentage of long-term survivors for alloT was 34.03% (figure1). Fig B shows rather good adequacy. The study of the impact of usual prognosis factors (age, time diagnosis-transplant, sex match, HLA match, CMV status, type of conditioning, BM or PBSC, ABO compatibility and disease status before transplantation) on the percentage of long-term survivors showed that only the status of disease at transplant had a significant impact: (CR vs SD or PD, HR: 0.11 [0.02–0.5] p=0.01 and PR vs SD or PD, HR: 0.30 [0.09–0.96] p=0.04). This study pointed out the possibility of curing B-CLL patients who responded to conventional chemotherapy with allogeneic transplantation rather than with autologous transplantation. Figure Figure Figure Figure

Two Cycles of Risk-Adapted Consolidation Leads to a Favorable Long-Term Prognosis in Patients with Acute Promyelocytic Leukemia After Standard AIDA Induction: Results From 141 Patients Treated in the SAL-AIDA-2000 Trial

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 765-765 ◽  
Author(s):  
Uwe Platzbecker ◽  
Ulrich Schuler ◽  
Martin Bornhäuser ◽  
Michael Kramer ◽  
Markus Schaich ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Promyelocytic Leukemia ◽  
Promyelocytic Leukemia ◽  
Induction Treatment ◽  
Term Survival ◽  
Consolidation Treatment ◽  
High Risk Patients ◽  
Risk Patients ◽  
Disease Free

Abstract Abstract 765 Background: The combination of ATRA and idarubicin (AIDA) for induction therapy of acute promyelocytic leukemia (APL) yields complete remission (CR) rates of > 90%. If this is followed by intensive consolidation treatment, about 85% of patients are disease free and alive after 6 years. In fact, three cycles of consolidation treatment are considered the therapeutic standard; however, it is unclear how much treatment intensity is necessary for long-term survival. In order to address this question, we analyzed the clinical course of patients enrolled into the APL study of the German Study Alliance Leukemia (SAL), which contained only two courses of consolidation. Patients and Methods: All patients ≥ 18 years diagnosed with cytogenetically confirmed APL were eligible for inclusion in the risk-adapted SAL-AIDA-2000 trial. Enrolled patients received standard induction treatment with ATRA (45 mg/m2/d until CR) and idarubicin (12 mg/m2 for 4 doses every other day). After CR, non-high-risk patients (WBC ≤ 10,000/μL) received daunorubicin (45/60 mg/m2 days 1–3, dose depending on age) as first consolidation and mitoxantrone (10 mg/m2 days 2–4) as second consolidation. High-risk patients received additional cytarabine in both consolidation cycles (100/200 mg/m2 continuous infusion over 7 days in 1st consolidation and 1000/3000 mg/m2 twice daily on 4 days in 2nd consolidation, dose depending on age). After 2 cycles of consolidation, all patients were scheduled for 24 months of maintenance with 6-mercaptopurin (90 mg/m2 daily), methotrexate (15 mg/m2 weekly), and ATRA (45 mg/m2 for 15 days every 3 months). The following outcomes were analyzed: CR rate, induction deaths, disease-free survival (DFS), and overall survival (OS). Results: Between January 1999 and October 2010, 141 patients were enrolled in the trial. The median age at diagnosis was 51 years (range, 19–82), and 41 (29%) patients had a WBC >10,000/μL (high risk). The CR rate was 92% in the entire cohort; 95% in patients ≤ 60 and 86% in patients > 60 years (p=0.082). No significant differences in CR rates were seen between high-risk and non-high-risk patients (88% vs 94%, p=0.213). Three patients died during induction treatment (2%). After a median follow up of 55 months, the median DFS and OS were not reached. The estimated 6-year DFS was 80% (95%–CI 72%–88%) in all patients; 84% in patients ≤ 60 and 72% in patients > 60 years (p=0.140). The estimated 6-year OS was 77% in all patients; 84% (95%–CI 76%–92%) in the younger and 62% (95%–CI 47%–78%) in the elderly group (p=0.004). No significant survival differences between the high-risk and the non-high-risk patients were observed, neither for DFS (6-year DFS 78% (95%–CI 64–93%) vs 81% (95%–CI 72%–91%), p=0.625) nor for OS (6-year OS 71% (95%–CI 57%–86%) vs 79% (95%–CI 70–89), p=0.207). Conclusions: Our results confirm the efficacy of a risk-adapted approach both in high-risk and non-high-risk APL patients. The similarity for DFS and OS times between these two groups demonstrate the efficacy of cytarabine added to anthracyclines during consolidation in high-risk patients. Both CR rates and survival outcomes are comparable to the results obtained in the AIDA0493 and AIDA2000 trials by the GIMEMA group, which used three cycles of higher-dosed consolidation. In light of the data, modification in number and intensity of consolidation cycles may result in a less toxic but equally effective option for the treatment of APL and should be considered for further evaluation in a randomized clinical trial. Disclosures: No relevant conflicts of interest to declare.

Impact of Chromosome 13 Deletion and Plasma Cell Load on Long-Term Survival of Patients with Multiple Myeloma Undergoing Autologous Transplantation

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5148-5148
Author(s):  
Esbjörn Paul ◽  
Tolga Sutlu ◽  
Evren Alici ◽  
Goesta Gahrton ◽  
Hareth Nahi
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Autologous Transplantation ◽  
High Dose ◽  
Prognostic Impact ◽  
Term Survival ◽  
Chromosome 13 ◽  
First Line Therapy

Abstract High-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) is the most common treatment for patients under 60–65 years of age with multiple myeloma (MM). In this study, we present a retrospective analysis of the prognostic impact of different factors in patients who have received this treatment as first line therapy in our centre. Abnormalities in chromosome 13 were identified by fluorescence in situ hybridization at the time of diagnosis. The median OS and PFS from transplantation time in the whole group of 193 patients were 90 and 48 months respectively. The median follow-up was 65 months (range: 6–186 months). The complete remission (CR) rate in patients with and without del(13) was 31% and 40% respectively whereas the median OS in patients with del(13) was 58 months but not reached in patients without del(13) (p=0.006). The PFS was 26 months in patients with del(13) and 84 months in those without del(13) (p=0.001). The transplantation related mortality was 2.5% both in the absence and presence of del(13). Patients who achieved CR following ASCT had longer OS and PFS when compared to those who only achieved partial remission. Thus, this study confirms the role of del(13) as a marker of poor prognosis. Multivariate analysis showed that the existence of del(13) was the only single independent factor effecting survival (p=0.001). In patients without del(13), the prognostic impact was even stronger when combined with the plasma cell load in the bone marrow (p=0.020), whereas the plasma cell load had no effect on survival of patients with del(13). Overall, the absence of del(13) in combination with low plasma cell infiltration at diagnosis predicts the best survival.

Therapeutic Relevance of CD34 Cell Dose in Blood Cell Transplantation for Cancer Therapy

2000 ◽  
Vol 18 (6) ◽  
pp. 1360-1377 ◽  
Author(s):  
Salvatore Siena ◽  
Roberta Schiavo ◽  
Paolo Pedrazzoli ◽  
Carmelo Carlo-Stella
Keyword(s):  
Growth Factors ◽  
Allogeneic Transplantation ◽  
Hematopoietic Growth Factors ◽  
Cell Content ◽  
Hematopoietic Stem ◽  
Graft Versus Host ◽  
Cell Dose ◽  
Large Numbers ◽  
Engraftment Failure

PURPOSE: To review recent advances in peripheral-blood progenitor-cell (PBPC) transplantation in order to define the optimal cell dose required for autologous and allogeneic transplantation. MATERIALS AND METHODS: A search of MEDLINE was conducted to identify relevant publications. Their bibliographies were also used to identify further articles and abstracts for critical review. RESULTS: The CD34+ cell content of a graft is regarded as an accurate predictor of engraftment success. Postchemotherapy autologous PBPC transplantation with ≥ 5 × 106 CD34+ cells/kg body weight leads to more rapid engraftment than does transplantation of lower cell doses. Further increases in transplant cell dose further accelerate platelet but not neutrophil engraftment. Evidence that long-term hematopoietic recovery may be more accurately predicted by the subpopulation of primitive progenitors transplanted suggests that the content of CD34+CD33− and long-term culture-initiating cells in cell collection samples may be important for predicting successful engraftment, particularly in patients with poor mobilization. Allogeneic transplantation has been limited by concerns regarding graft-versus-host disease and the use of hematopoietic growth factors in donors. The risk of graft rejection and engraftment failure after HLA-mismatched allogeneic transplantation may be overcome by intensive chemoradiotherapy and the infusion of large numbers of T cell–depleted hematopoietic stem cells. CONCLUSION: An optimal cell dose of ≥ 8 × 106 CD34+ cells/kg seems to be recommended for autologous PBPC transplantation. This dose facilitates the administration of scheduled chemotherapy on time and reduces the demand for other supportive therapies. A combination of growth factors may enable patients with poor mobilization to achieve a collection sufficient to allow transplantation. The optimum PBPC dose for allogeneic transplantation remains to be defined.

scholarly journals Lower Doses of Plerixafor Use Is Sufficient to Effectively Mobilize PBSC (Peripheral Blood Hematopoetic Stem Cells) When Compared to Standard Administration

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5830-5830
Author(s):  
Hakan Goker ◽  
Eylem Eliacik ◽  
Fevzi Altuntas ◽  
Emre Tekgunduz ◽  
Evren Ozdemir ◽  
...  
Keyword(s):  
Stem Cells ◽  
Peripheral Blood ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Autologous Transplantation ◽  
Cost Effective ◽  
Hematopoietic Stem ◽  
Retrospective Comparison ◽  
Autologous Hct

Abstract Background: Plerixafor (CXCR4 chemokine receptor antagonist), is indicated to mobilize hematopoietic stem cells (HSCs) to the peripheral blood for collection and subsequent autologous transplantation in patients who are poor mobilizers. In this retrospective analysis, we compared the efficacy of plerixafor 0.24 mg/kg by subcutaneous (SC) injection (1-2 doses) versus plerixafor (3-4 doses) 0.24 mg/kg by SC injection in terms of their effect on the hematopoietic recovery in hematopoietic cell transplantation (HCT). Methods: We retrospectively reviewed the peripheral blood stem cell (PBSC) collections of 40 consecutive lymphoma and multiple myeloma patients who underwent autologous HCT, who had previously mobilized poorly and were given plerixafor for mobilization. Twenty-six patients received 1-2 doses of plerixafor and 14 patients received 3-4 doses. All patients gave written informed consent for the procedure. Successful engraftment time was defined as neutrophils >0.5x 109 cells/L, platelets>20 x109 cells/L for three consecutive days. SPSSincver. 20 is used for statistics. Results: All of the 40 patients were mobilized promptly after plerixafor administration without any problem. The mean amount of autologous CD34+ PBSC was 3,8 x 10(6)/kg versus 3,2 x 10(6)/kg, for 1-2 doses of plerixafor administration ve3-4 doses, respectively(p=0,4). Median times to the neutrophil engraftment to >0,5x 109/L were 12 and 10 days for the 1-2 doses and 3-4 doses, respectively (p=0,2). Additionally, median times to the platelet engraftment to >20x 109/L were 14 and 15 days for the 1-2 doses and 3-4 doses, respectively (p=0,6). Conclusions: These data show that the lower doses, i.e. 1-2 days of plerixafor administration evaluated in this study are sufficient to mobilize HSCs. This retrospective comparison suggest that larger prospective studies comparing two days vs. four days of plerixafor should be performed in order to further elucidate the role of two days of plerixafor use in HSC mobilization, and hence would a relatively cost effective way of mobilization in poor mobilizing patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Alloantigen presenting function of normal human CD34+ hematopoietic cells

Blood ◽  
1996 ◽  
Vol 88 (7) ◽  
pp. 2619-2675 ◽  
Author(s):  
D Rondelli ◽  
RG Andrews ◽  
JA Hansen ◽  
R Ryncarz ◽  
MA Faerber ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Cell Activation ◽  
Autologous Transplantation ◽  
Allogeneic Transplantation ◽  
Hematopoietic Stem ◽  
Hla Dr ◽  
Cd34 Cells ◽  
Marrow Cells

The identification of the CD34 molecule, expressed almost exclusively on human hematopoietic stem cells and committed progenitors, and the development of CD34-specific monoclonal antibodies have made procurement of relatively pure populations of CD34+ marrow cells for autologous transplantation feasible. Characterization of the immunogenicity of CD34+ marrow cells may facilitate the design of successful strategies to use these cells for allogeneic transplantation. CD34+ marrow cells from normal volunteers were enriched to greater than 98% purity by immunoaffinity chromatography on column followed by fluorescence-activated cell sorting. Purified CD34+ cells were tested for expression of HLA-DR and other accessory molecules, and function in hematopoietic colony growth and mixed leukocyte culture (MLC) assays. Greater than 95% CD34+ cells were positive for HLA-DR and 74% +/- 10% were highly positive for CD18, the common beta-chain of a leukointegrin family. CD34+/CD18- cells were small, agranular lymphocytes which contained the majority of precursors for colony-forming cells detected in long-term cultures. They produced almost no stimulation of purified T cells from HLA-DR-incompatible individuals in bulk MLC or in limiting dilution assay. In contrast, CD34+/CD18+ cells were large, were enriched for cells forming mixed colonies in short- but not long-term assays, and were capable of stimulating allogeneic T cells. CD86, a natural ligand for the T-cell activation molecule CD28, was coexpressed with CD18 in 6% +/- 3% of CD34+ cells. CD34+/CD86+ cells, but not CD34+/CD86- cells, exhibited strong alloantigen presenting function. Thus, pluripotent hematopoietic activity and alloantigen presenting function are attributes of distinct subsets of CD34+ marrow cells. CD34+/CD18- or CD34+/CD86- cells may be more effective than either the whole CD34+ population or unseparated marrow in engrafting allogeneic recipients and may also facilitate induction of tolerance.

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