Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Versus Conventional Chemotherapy in Patients with Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS) Attaining Complete Remission (CR1) Post Induction Chemotherapy: a Retrospective Case Control Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1125-1125
Author(s):  
Yvonne A Efebera ◽  
Hagop M. Kantarjian ◽  
Borje Andersson ◽  
Sherry Pierce ◽  
Leandro De Padua Silva ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Chemotherapy Group

Abstract The role of allogeneic HSCT in patients with AML/MDS in CR1 is not well established. Historically, high rates of non-relapse mortality (NRM) associated with HSCT have negatively counterbalanced the reduced relapse rate associated with the graft-versus leukemia effect. We hypothesized that if NRM is reduced, allogeneic HSCT will improve relapse-free survival (RFS) when compared to chemotherapy alone. Here we compared outcomes of patients treated with busulfan 130 mg/m2 and fludarabine 40 mg/m2 for 4 days (our ablative regimen with the lowest NRM rate) and matched controls treated without HSCT. Methods: Between January, 2001 and December, 2004, 36 patients with AML (n=28) or high-risk MDS (n=8) in CR1 were transplanted. Year 2004 was chosen as the cutoff to allow for significant follow up time. Controls were 110 patients treated in the leukemia department without HSCT between 1980 and 2004, selected to match according to age, cytogenetics, and time in CR1 (in order to compensate for the time in CR1 that preceded HSCT, which was a median of 3.3 months, range 0.36–12.4 months). All patients received induction regimen containing high dose cytarabine. Eligible for HSCT were patients in remission that did not have good prognosis cytogenetics that had a performance status of 0 or 1, adequate organ function, no uncontrolled infection and age 18–65 years. Primary end point was RFS (measured from CR1 date to relapse or death). Results: Median age was 42 years in both groups (range 21–62). Proportion of patients with intermediate risk and high-risk cytogenetics in the transplant and chemo groups was as follows: 67% versus 72%, and 33% versus 28%, respectively. The median time from diagnosis to CR1 was 1.5 month (range, 0.6–17.2) and 1.15 month (range, 0.13–5) in the HSCT and chemotherapy groups respectively. Patients in the control group had de novo AML in 92% of the cases (n=102) versus 64% in the HSCT cohort (n=23), while more patients in the transplant group had secondary AML or MDS (36% vs 8%). Donors were HLA matched related in 22 cases (61%), and a matched unrelated donor in 12 patients (39%). Stem cell source was the peripheral blood (n=20; 56%) or bone marrow (n=16, 44%). Median follow-up of surviving patients is 5.2 years for the HSCT (range, 2.4–7) versus 9.1 years (3.9–21) for the chemotherapy group, respectively. Twelve HSCT patients have died (33%), versus 76 (69%) in the chemotherapy group. Relapse occurred in 12/36 patients (33%) in the HSCT group versus 79/110 (72%) in the control group. NRM in the HSCT cohort was zero at 100 days, 7% at one year and 15% at 3 years (1 patient died of chronic GVHD and 1 died of pneumonia). RFS is shown in the picture. RFS of transplant patients remains superior if we only used control patients treated in the same time frame in which the transplants were performed (ie, year 2001 to 2004; p=0.0003) Conclusion: These results indicate improved survival with HSCT and support the conduct of a randomized comparison of chemotherapy versus allogeneic HSCT using Busulfan Fludarabine preparative regimen for AML in CR1. Figure Figure

Efficacy of Reduced Intensity Conditioning (RIC) with FLU-BU-ATG and Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) for Pediatric ALL.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2314-2314 ◽  
Author(s):  
Reggie Duerst ◽  
David Jacobsohn ◽  
William T. Tse ◽  
Morris Kletzel
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Chronic Gvhd ◽  
High Dose ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Pediatric All ◽  
Very High ◽  
Reduced Intensity

Abstract Reduced Intensity Conditioning (RIC) regimens prior to allogeneic HSCT have gained acceptance in the treatment of adults with myelodysplasia, leukemia and multiple myeloma. RIC reduces the risk for regimen related morbidity and mortality enabling patients with pre-existing medical conditions that would have been precluded from allogeneic HSCT to attempt a curative approach. The resilience of pediatric patients (pts) following high-dose conditioning regimens and the concern that ALL cells are inherently more resistant to a graft-vs-leukemia effect have limited accrual of pediatric ALL pts to RIC protocols despite the potential benefit for reduced long-term morbidity. We report the experience of 10 pediatric ALL pts (6 M, 4 F, median age 9.5 years) treated for recurrent ALL with RIC and allogeneic HSCT. A uniform RIC regimen comprised of fludarabine, 30 mg/m2 for 6 consecutive days (days −10 through −5), followed by intravenous busulfan, 0.8 – 1 mg/kg for 8 doses or targeted AUC 4000 μMol*min for 2 doses (days −5 and −4) and equine ATG, 40 mg/kg or rabbit ATG, 2 mg/kg for 4 days (days −4 through −1) was administered. Pts with prior CNS involvement received whole brain (2400 cGy) and spinal (1800 cGy) irradiation immediately prior to the RIC. Stem cell sources included 7 unrelated donors and 3 matched sibs. 9 of 10 stem cell donations were peripheral blood stem cells (PBSC). The median cell doses infused were 6.5 x 108 MNC/kg and 4.2 x 106 CD34+ cells/kg. Graft-versus-host disease (GVHD) prophylaxis was cyclosporin A (CsA) alone in 5 patients, CsA and mycophenolate mofetil in 5 pts. Growth factor support was not used. Each of the pts had at least two very high-risk features--prior HSCT (n = 6), CR > 3/refractory disease (8), prior CNS disease (6), Ph+ (2), pre-exisiting neurologic (1) or cardiac (1) dysfunction or aspergillous infection (1). Full donor chimerism was achieved in 9 of 10 with a median time to reach an ANC >500/μl of 16 days (range 11–62) and an unsupported platelet count > 20,000/μl was achieved in 8 of 10 at a median of 25 days (15–67). 2 pts developed Gr IV acute GVHD, 2 of 5 pts surviving more than 100 days developed chronic GVHD. Only 3 patients have relapsed: 1 refractory T-ALL pt recurred day +27 and 2 Ph+ pts had a molecular relapse day +61 and +196. The latter pt is in subsequent continuous molecular remission for over 1 year on imatinib therapy. 6 pts have died, 5 in the first 100 days of HSCT from complications of GVHD (2), relapse (1), pulmonary failure (in 1 pt S/p 3 prior allogeneic HSCT) and PTLD (1). 1 pt succumbed from complications of chronic GVHD day +756. The RIC regimen and supportive care are primarily an outpatient experience. During the first 30 days post HSCT, pts spent an average of only 9 days in hospital (23 of the first 100 days). Despite very high-risk features, 4 of 10 pts survive (3 CCR) at a median of 500 days post HSCT. Thus, RIC and allogeneic HSCT also offers promise for efficacy in pediatric ALL.

Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3228-3228
Author(s):  
Elizabeth Berger ◽  
Christopher Seet ◽  
Mala Parthasarathy ◽  
Tulio Rodriguez ◽  
Scott E. Smith ◽  
...  
Keyword(s):  
Stem Cell ◽  
Standard Dose ◽  
Stem Cell Mobilization ◽  
Phase Iii ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Gm Csf ◽  
Cell Mobilization

Abstract Abstract 3228 Poster Board III-165 Introduction Using standard dose G-CSF (10 μg/kg) for stem cell mobilization, 25-40% of patients, deemed to be hard to mobilize based on prior therapy, will not collect sufficient HSC (> 2-2.5 × 106 CD34/kg) to proceed to a prompt autotransplant. Strategies to improve CD34/kg yields have included dose escalating G-CSF up to 30 μg/kg or combining G-CSF and GM-CSF. While dose escalated G-CSF is effective in increasing CD34 yields in normal donors as is the combination of G-CSF and GM-CSF, their comparative value in pre-treated patients has not been tested. To determine the value of these strategies, we performed a randomized comparison of high dose G-CSF (30 μg/kg as 2 doses 12 hours apart), to the combination of simultaneous single daily doses of G-CSF (10 μg/kg) plus GM-CSF (5 μg/kg), to a control group receiving G-CSF at an equivalent total dose of cytokine to the combination arm (15μg/kg) as a single dose. Patients and Methods Patients were eligible if heavily pre-treated, defined as: a minimum of 10 total cycles of combination chemotherapy and two prior regimens, or a total of 6 chemotherapy cycles if the patient also received RT to marrow bearing sites, platinum-based chemotherapy or 2 or more cycles of any BCNU or fludarabine containing regimen. Baseline WBC had to be > 3000/μl, ANC > 1500/μl and a platelets > 100,000/μl. Twelve liter aphereses began on day 5 of mobilization, and continued until ≥ 4 × 106 CD34/kg were collected or a maximum of 5 aphereses. Patients typically proceeded to transplant if they had ≥ 2.5 × 106 CD34/kg collected and were always re-mobilized if they collected < 2.0 × 106 CD34/kg. CD34 subsets (CD34+/CD33- and CD34+/CD38-) were also assessed for the 3 groups to determine if more primitive HSC were mobilized by the 2 novel strategies. The sample size was calculated based as follows: 60% of the control group would collect 2.5 × 106 CD34/kg and this would rise to 90% in one or both study arms. The detection of such differences with a power of 80% and a 2-sided alpha level of 0.025 required a total sample of 120 patients. Results A total of 120 patients were randomized; 119 were eligible. Patient demographics, shown in the Table, were matched among the three groups: The % of patients collecting ≥2.5 × 106 CD34/kg was: standard G: 60%, high dose G: 57% (p = 1.0), G + GM: 41% (p = 0.1). Median CD34 collected in first mobilization were, 3.6 × 106/kg, 3.0 × 106/kg (p = 0.22) and 2.0 × 106/kg (p = 0.05) respectively in a median of 4, 4, and 5 aphereses (p = NS). Re-mobilization rates: standard G; 37.5%, high dose G: 35%; G + GM: 50% (p = NS). Total median CD34 collected from first and any second mobilizations were: standard G: 4.8 × 106/kg, high dose G: 3.9 × 106/kg, and G + GM: 3.5 × 106/kg. One patient in the standard G arm and 3 in high dose G did not proceed to transplant due to poor initial mobilization and progression in 2, and one each for progression or poor mobilization alone. There were no significant differences in median engraftment times: for ANC, 10, 11 and 15 days respectively for the standard G-, high dose G- and G + GM arms and for platelets, 11, 13 and 14 days respectively. The overall survivals @ the median f/u time of 37 months were 59.8%, 61.8% and 48.1% respectively (p = 0.272) for the three groups. The % primitive HSC (CD34+/CD33- and CD34+/CD38-) from the first mobilization were identical in the 3 patient groups. Conclusions We found no advantage to dose escalated G-CSF nor to the combination of G-CSF and GM-CSF to mobilize HSC for autotransplantation in heavily pre-treated patients. We also did not find higher numbers of more primitive CD34 subsets mobilized by these newer strategies. Alternative approaches, e.g. the combination of plerixifor + standard dose G-CSF (Stiff et al: BBMT; 15:249-56, 2009) would appear to be the preferred method of initial HSC mobilization for heavily pre-treated patients. Disclosures Stiff: Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Allogeneic Hematopoietic Stem Cell Transplantation For Severe Neuromyelitis Optica

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5539-5539 ◽  
Author(s):  
Raffaella Greco ◽  
Attilio Bondanza ◽  
Luca Vago ◽  
Lucia Moiola ◽  
Paolo Rossi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
High Dose ◽  
B Cell Depletion ◽  
Immune Repertoire ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract Background Neuromyelitis Optica (NMO), also known as Devic’s disease, is a rare inflammatory and demyelinating disorder of the central nervous system characterized by recurrent attacks of optic neuritis (ON) and longitudinally extensive trasverse myelitis (LETM). Previously considered as a severe variant of multiple sclerosis, NMO has been recently recognized as a distinct disorder associated with peculiar pathogenic auto-antibodies to aquaporin-4 (AQP4). Despite transient control of disease activity, standard treatments are often followed by relapses with accumulating disability and ultimately a poor prognosis. Thus, new therapeutic strategies for NMO are warranted. Hematopoietic Stem Cell Transplantation (HSCT) can induce stable remissions in patients with severe treatment-refractory Autoimmune Diseases. Here we report our investigational experience on allogeneic HSCT in two patients with severe and refractory forms of the disease. Methods Both treated patients had aggressive forms of NMO and serum positivity for AQP4 antibodies. Upn#1 is a 30 yrs old male affected by severe relapsing LETM, with paraparesis and thoracic spinal cord lesion on magnetic resonance imaging (MRI). Upn#2 is a 28 yrs female with recurrent attacks of ON and LETM. Both had received several lines of treatment without benefit, including high-dose corticosteroids, cyclophosphamide, rituximab, natalizumab, alemtuzumab, plasma exchange, high-dose thiotepa/cyclophosphamide and/or BEAM with Anti-Thymocyte Globulin (ATG) and cyclosporine followed by autologous HSCT rescue. Before HSCT the two patients showed an Kurtzke Expanded Disability Status Score (EDSS) of 6 (assistance required to walk) and 8.5 (restricted to bed, paraplegia) respectively, while both of them presented active contrast enhancing lesions on MRI and positivity for the pathogenic AQP4 auto-antibodies. Upn#1 underwent allogeneic HSCT from his HLA-identical sibling, while Upn#2 from a matched unrelated donor. Conditioning regimen consisted of full-dose treosulfan and fludarabine. Graft versus host disease (GvHD) prophylaxis combined ATG-Fresenius with cyclosporine and a short course of methotrexate (Upn#1) or mycophenolate and rapamycin (Upn#2); B cell depletion of both patients and graft was obtained by rituximab. Results Hematopoietic recovery occurred in both patients within day 30, and was accompanied by rapid achievement of full donor chimerism. Each patient experienced an episode of febrile neutropenia and one of them a CMV reactivation, both responsive to medical therapy; no serious adverse events were reported. None of the patients experienced neither acute nor chronic GvHD. MRI demonstrated the disappearance of the inflammatory lesions, without evidence of new ones. The immunological data obtained from the follow-up of these two patients suggest that allogeneic HSCT can alter the course of NMO through several concurring mechanisms: the eradication of autoreactive cell clones by high-dose chemotherapy and by the in vivo T and B cell depletion used for conditioning, the disappearance of the pathogenetic anti-AQP4 antibodies and achievement of a stable full-donor hematopoietic chimerism by donor T cell-mediated alloreactivity; the re-establishment of thymic central tolerance and renewal of the immune repertoire. Strikingly, these results correlated with a marked improvement of neurological functions in both treated patients. In UPN#1 EDSS dropped from 6 to 3.5 (fully ambulatory but with moderate disability in one functional neurological system), while in UPN#2 EDSS decreased from 8.5 to 7.5 (unable to take more than a few steps, restricted to wheelchair). At last follow-up (48 and 36 months after HSCT, respectively), both patients are alive, well and relapse-free. Conclusions These findings suggest that allogeneic HSCT may be beneficial in patients who have aggressive forms of NMO, by renewing the immune repertoire of T- and B-cells, thus reducing disease activity and arresting disability progression. The preliminary evidence of long-term disease control in these two refractory patients paves the way for further prospective phase I-II clinical trials to validate allogeneic HSCT as promising novel option for aggressive forms of NMO. Disclosures: Bonini: MolMed S.p.A: Consultancy.

Update of a phase II, multicenter study of high-dose chemotherapy with autologous stem cell transplant followed by maintenance romidepsin for T-cell lymphoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7533-7533
Author(s):  
Niloufer Khan ◽  
Farhad Khimani ◽  
Andrei R. Shustov ◽  
Mazyar Shadman ◽  
Jia Ruan ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Multicenter Study ◽  
Stem Cell Transplant ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem

7533 Background: Peripheral T-cell lymphomas (PTCL) have suboptimal outcomes with conventional chemotherapy. Autologous hematopoietic stem cell transplant (AHCT) is a therapeutic strategy for patients in first complete or partial remission (CR1 or PR1), with median progression-free survival (PFS) after AHCT of 36-48% by intent to treat (d’Amore et al JCO 2012, Reimer et al JCO 2009). Romidepsin (romi) is a histone deacetylase inhibitor approved for treatment of relapsed/refractory T-cell lymphoma. We present updated data of the first multicenter study to evaluate PFS of patients (pts) receiving maintenance therapy with romi after AHCT. Methods: This was a phase 2, open-label, investigator-initiated study (expected PFS 45%, desired PFS 70%; success achieved if 15 or more pts out of 25 were progression-free at 2 years post-AHCT). 26 pts transplanted in CR1 or PR1 were evaluable for the primary endpoint of 2-year PFS (Cohort 1, Table). An exploratory cohort (Cohort 2, n=7) enrolled pts either transplanted ≥ CR/PR2 (n=5) or with high risk histologies (n=2). Pts underwent AHCT with carmustine, etoposide, cytarabine and melphalan (BEAM) conditioning. Maintenance romi 14 mg/m2 started days 42-80 post AHCT; every other week through 6 mon, every 3 weeks through 1 year and every 4 weeks through 2 years post AHCT. PFS was estimated by Kaplan-Meier. Results: 47 pts consented; 13 did not receive romi (no AHCT, n=2; relapse before romi, n=3; cardiac comorbidity, n=3, patient declined, n=5). 1 consented pt did not have PTCL. 15 out of the first 25 pts in Cohort 1 were progression free after 2 years; median follow up of 31 mon (21 - 36 mon). Estimated 2-year PFS was 62% (45-83%, 95% CI); median PFS 30 mon (12.0- NA, 95% CI). In Cohort 2, estimated 2-year PFS was 43% (18 – 100, 95% CI); median follow up of 30 mon (range, 24 – 37 mon); median PFS 14 mon (5 – NA, 95% CI). Across cohorts, 5 pts required dose reduction. The most common toxicities (≥10% of pts, all grades) were fatigue (n=24, 73%), decreased platelets (n=16, 48%) and anemia (n=16, 48%). Conclusions: While the study did not meet its desired primary efficacy endpoint, maintenance romi was well-tolerated with an estimated 2-year PFS of 62%, greater than historical data. A larger, randomized study would be needed to determine the superiority of this approach. Clinical trial information: NCT01908777. [Table: see text]

The Superiority of Allogeneic Hematopoietic Stem Cell Transplantation From Unrelated Donor Over Chemotherapy As Post-Remission Treatment for Patients with High-Risk Acute Lymphoblastic Leukemia in First Remission

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1986-1986
Author(s):  
Jiong Hu ◽  
han-Bo Dou ◽  
Ling Wang ◽  
Wei Tang
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Relapse Rate ◽  
Lymphoblastic Leukemia ◽  
P Value ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Chemotherapy Group

Abstract Abstract 1986 For adult patients with acute lymphoblastic leukemia (ALL), allogeneic hematopoietic stem cell transplantation (allo-HSCT) from HLA-matched related donor (MSD) is recommended for standard and high-risk patients. The role of unrelated donor transplantation (URD) is not fully determined. In this single-center retrospective analysis, we included all consecutive adult patients with high-risk ALL in 1st complete remission (CR) without sibling donor between Jan 2007 to June 2012. Overall, 74 patients were included in the analysis in which 32 patients received URD allo-HSCT during 1st CR with busulfan-cyclophophamide preparation regimen and in vivo T cell depletion with anti-T-lymphoglobulin (ATG). The median time from remission to transplantation was 4.5 months (3∼13). Forty-two patients in the chemotherapy group with 1st CR more than 6 months received consolidation chemotherapy alone either due to lack of suitable URD (n=21), refuse to URD search (n=14), unwillingness to undergo transplantation with available URD (n=5) and donor refuse to donate (n=2). Salvage allo-HSCT was allowed after relapse and actually 5 patients in the chemotherapy group received transplantation from URD donor (n=2) or haplo-identical donor (n=2) in the subsequent remission. The clinical characteristics such age, sex, initial WBC, and Philadelphia chromosome are all distributed equally in the two groups. With a median follow-up of 18 months for the whole group, 30 patients relapsed with estimated 3-year relapse rate (RR) at 58.1±8.5%. The 3-year event-free survival (LFS), non-relapse mortality (NRM) and overall survival (OS) were 38.0±7.9%, 11.1±4.4% and 46.0±9.0% respectively. In the URD allo-HSCT group, RR was 30.6±11.4% which was significantly lower than chemotherapy group (80.5±10.1%, p<0.001) while NRM was higher (16.4±6.7% vs. 0, p=0.028). Overall, 3-year LFS was superior in URD allo-HSCT group compared to chemotherapy (57.8±10.6% vs. 19.5±10.5%; median not reached vs. 13 months, p=0.002) and 3-year OS was also improved in URD allo-HSCT group (63.5±13.3%, median not reached versus 31.6±10.6%, median 24 months, p=0.016). Based on our data, URD allo-HSCT significantly reduced the relapse rate in high-risk ALL and the benefit translated into improvement in both LFS and OS. Prospective randomized study based on availability of HLA matched URD is warranted to confirm the exact role of URD transplantation in adult ALL. Table 1. Patient's characteristics Chemotherapy URD-allo-HSCT P value No of patients N=42 N=32 Median Follow-up (months) 15 (7.7∼48) 22 (8.2∼49) Sex (M/F) 19/23 21/11 0.08 Age 24.5 (16∼60) 25 (16∼57) 0.10     >35 14 9 0.61     <=35 28 23 Initial WBC (×109/L) 80.3 (15.3∼97.9) 61.5 (3.2∼98.4) 0.12 Cytogenetics     Ph+ 8 10 0.33     Ph− 33 22 Table 2. Clinical outcome in different treatment strategies Chemotherapy URD-allo-HSCT P value No of patients N=42 N=32 OS 31.6 ± 10.6% 63.5 ± 13.3% 0.016     median 24.9 months not reached LFS 19.5 ± 10.5% 57.8 ± 10.6% 0.002     median 13.2 months not reached Relapse rate 80.5 ± 10.1% 30.6 ± 11.4% <0.001 NRM 0% 16.4 ± 6.7% 0.028 Disclosures: No relevant conflicts of interest to declare.

Prospective Evaluation of Azacitidine Maintenance Following Allogeneic Hematopoietic Stem Cell Transplantation in Patients with High-Risk Acute Myeloid Leukemia and Myelodysplastic Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5476-5476 ◽  
Author(s):  
Harinder Gill ◽  
Albert Kwok Wai Lie ◽  
Yok Lam Kwong ◽  
Anskar Y.H. Leung
Keyword(s):  
Acute Myeloid Leukemia ◽  
Stem Cell ◽  
High Risk ◽  
Myeloid Leukemia ◽  
Chronic Gvhd ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Poor Risk ◽  
Acute Myeloid

Abstract Introduction and aim. Relapse following allogeneic hematopoietic stem cell transplantation (HSCT) is a major cause of treatment failure and is associated with a poor prognosis. Overall survivals are around 50% at 5 years following allogeneic HSCT in intermediate and high risk AML. Survivals remain less than 20% in poor-risk and very poor-risk patients based on the cytogenetic profile. Thus, prevention of relapse following allogeneic HSCT remains an unmet clinical need. Low-dose azacitidine maintenance post-HSCT has been shown to augment graft-versus-leukemia effect and may prolong survivals. We aim to prospectively evaluate the effect of azacitidine maintenance following allogeneic HSCT in high risk AML and MDS. Method. Consecutive patients with high-risk acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) in remission following first allogeneic HSCT or second allogeneic HSCT (from the original donor) were recruited. High risk AML in this study comprised patients with poor risk karyotype, secondary AML transformed from underlying MDS, presence of fms-like tyrosine kinase 3-internal tandem duplication (FLT3 -ITD) and non-remission before HSCT. Azacitidine was administered at 100mg daily for 3 days per cycle every 28 days until progression or a maximum of 8 cycles. The clinicopathologic and treatment characteristics were determined. The occurrence of graft-versus-host disease (GVHD) was determined. DNA chimerism was determined in the bone marrow before the initiation of azacitidine, after 4th and 8th cycles of azacitidine and at 1 year. DNA chimerism was determined by quantification of polymorphic short tandem repeat sequences. The progression-free survival (PFS) and overall survival (OS) were determined by Kaplan-Meier analysis. Results. Thirty-four patients with high-risk AML (N=31) and MDS (N=3) were recruited. The median duration of follow-up was 14 months (range: 2 - 44 months). Twenty-two patients received azacitidine maintenance after first allogeneic HSCT, whereas 12 patients received azacitidine maintenance after a second allogeneic HSCT from the same donor following relapse from a first allogeneic HSCT For patients receiving azacitidine after first HSCT, at a median follow-up of 18.5 months (range: 5- 36 months), the median PFS was not reached, and the median OS was 32 months (95% confidence interval [C.I.]: 24.85-39.15). The 24-month PFS and OS were 66.1% and 73.2% respectively. Acute and chronic GVHD occurred in 7 (31.8%) and 17 patients (77%). For patients receiving azacitidine after second HSCT, at a median follow-up of 14 months (range: 9 - 46 months), the median PFS and OS were 9 months (95% C.I.:6.94-11.04) and 14 months (range: 11.77 - 16.23 months). The 24-month PFS and OS were 25% and 14% respectively. Acute and chronic GVHD occurred in 1 (8.3%) and 5 (41.7%) patients respectively. In both groups, 100% donor chimerism was achieved during azacitidine maintenance. Conclusion. Azacitidine maintenance following first allogeneic HSCT resulted in favorable 2-year survivals in selected patients with high-risk AML and MDS. Nevertheless, survivals were poor despite azacitidine maintenance after second allogeneic HSCT from the same donor. Full donor chimerism was maintained during azacitidine maintenance. Disclosures No relevant conflicts of interest to declare.

scholarly journals Nonmyeloablative Versus Myeloablative Allogeneic Hematopoietic Stem Cell Transplant for GATA2 Deficiency

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1247-1247 ◽  
Author(s):  
Jennifer Cuellar-Rodriguez ◽  
Dennis D. Hickstein ◽  
Jennifer K. Grossman ◽  
Mark Parta ◽  
Juan Gea-Banacloche ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Gata2 Deficiency ◽  
Related Donor

Abstract Background: Mutations in the zinc finger transcription factor GATA2 are responsible for: MonoMAC, monocytopenia with nontuberculous mycobacterial (NTM) infections; DCML, dendritic cell, monocyte and lymphoid cell deficiency; Emberger's syndrome with lymphedema and monosomy 7; and familial myelodysplastic syndrome (MDS)/acute myelogenous leukemia (AML). Allogeneic hematopoietic stem cell transplant (HSCT) is the only definitive therapy for GATA2 deficiency. Methods: We used matched related donors (MRD), matched unrelated donors (URD), umbilical cord blood (UCB), and haploidentical related donors in allogeneic HSCT for GATA2 deficiency. Fourteen patients received a nonmyeloablative conditioning regimen (4 MRD, 4 URD, 4 UCB, and 2 haplo donors). Five patients received a myeloablative conditioning regimen (1 MRD, 2 URD, and 2 haplo donors). In the nonmyeloablative group, MRD and MUD recipients received fludarabine and 200cGy of total body irradiation (TBI), UCB recipients received cyclophosphamide 50mg/kg, fludarabine 150 mg/m2, and 200cGy of TBI, and haploidentical related donor recipients received cyclophosphamide 29 mg/kg, fludarabine 150 mg/m2, and 200 cGy TBI. In the myeloablative group, MRD and URD received busulfan 12.8 mg/kg and fludarabine 160 mg/m2, and haploidentical related donors received the same regimen as in the nonmyeloablative regimen except for the addition of two days of busulfan 6.4 mg/kg total dose. Nonmyeloablative MRD and URD recipients received tacrolimus and sirolimus post-transplant, and myeloablative MRD and URD recipients received tacrolimus and short course methotrexate post-transplant. All haploidentical related donor recipients received cyclophosphamide 50 mg/kg/day on days + 3 and +4 followed by tacrolimus and mycophenolate mofetil. Three patients in the nonmyeloablative cohort required one or more rounds of pre-transplant chemotherapy because of an increased number of blasts, whereas none of the 5 patients in the myeloablative arm required pre-transplant chemotherapy. Results: In the nonmyeloablative cohort, 8 of 14 (57%) of patients are alive at a median follow-up of 3.7 years (range 12 months to 5 years). One MRD recipient died of GVHD and one relapsed, one URD recipient rejected the donor stem cells and died, three UCB recipient died (one rejection, one early death, and one donor cell leukemia), and one haploidentical recipient died from regimen-related toxicity. All 5 patients (100%) in the myeloablative group, including two recipients of haploidentical related donors, are alive at a median follow-up of 9.2 months (range 6 to 12 months). All patients who survived had complete reconstitution of the monocyte, NK, and B-lymphocyte compartments, the three cell compartments that were severely deficient pre-transplant, and all had reversal of the infection susceptibility phenotype, characteristic of the disease. In particular, there were no recurrences of non-tuberculous mycobacterial (NTM) infections. Conclusions: Nonmyeloablative HSCT results in reversal of the hematologic and clinical manifestations of GATA2 deficiency. However, a more intensive conditioning regimen with busulfan resulted in more uniform engraftment, a reduced risk of relapse, avoidance of pre-transplant chemotherapy, and a low regimen-related toxicity. We anticipate that with the use of a high-dose regimen with busulfan, the replacement of UCB with haploidentical related donors, and HSCT earlier in the clinical course, before significant organ damage or clonal evolution of MDS to AML or CMML, the outcome of allogeneic HSCT in patients with GATA2 deficiency will continue to improve. Disclosures No relevant conflicts of interest to declare.

scholarly journals Relapsed Follicular Lymphoma Treatment - with or without Hematopoietic Stem Cell Transplant?

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5893-5893
Author(s):  
Dulcineia Pereira ◽  
Carolina Teixeira ◽  
Sofia Ramalheira ◽  
Patricia Rocha ◽  
Claudia Moreira ◽  
...  
Keyword(s):  
Stem Cell ◽  
Treatment Strategy ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Histological Grade ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Autologous Hsct

Abstract BACKGROUND: The best treatment strategy in patients with relapsed Follicular Lymphoma (FL) remains controversial. The incorporation of rituximab (R) in the 1st line chemotherapy (CT) regimen and in treatment relapse resulted in better progression-free survival (PFS) but the benefit in overall survival (OS) was observed in only one trial (Hiddemann W. et al, Blood 2006). Hematopoietic stem cell transplant (HSCT) is the only treatment potentially curative, although the ideal time for its implementation remains undefined. AIM: Evaluation of the best treatment strategy and the impact of HSCT in PFS and OS in patients with relapsed FL. METHODS: Retrospective study including 85 patients with relapsed FL followed at a cancer care center between 2000-2012. Selection criteria: treatment naïve patients with the diagnosis of FL; absence of histological transformation at diagnosis and/or during the 1st line treatment. Survival analysis using the Kaplan-Meier method. Type of response defined according to NCCN criteria. RESULTS: Median follow-up of 64 months [4-158]. Disease progression after the 1st line CT was documented in 85 patients (median age 51 years [28-78], 42.4% male). 64 of the 85 patients had an Ann Arbor stage III-IV, of which 85.9% with follicular pattern, 95.3% grade 1/2 and 43.8% FLIPI ≥ 3. All patients underwent one or more CT regimens containing R, except in one case. In this study, 27.1% (n = 23) patients with age ≤ 60 years were submitted to HSCT (52.2% allogeneic HSCT from a related donor versus 47.8% autologous HSCT), almost all with ≥ 2 prior lines of CT (95.6%, n = 22). 78.3% (n = 18) had a CR or PR> 75% at the time of HSCT, and one death related to graft versus host disease was registered. Patients undergoing HSCT had a better PFS than those not transplanted (p = 0.022). A significant improvement in OS was observed in the HSCT subgroup (p = 0.007), especially in those with stage III-IV (p = 0.006). The type of HSCT had no impact on PFS and OS (p> 0.05), perhaps due to the small number of patients and short follow-up. By univariate Cox regression analysis, the number of regimens of CT before HSCT and the histological grade were independent predictors of PFS (p <0.05). The age and the histological grade were independent predictors of OS (p <0.05). CONCLUSION: In this study, HSCT improved PFS and also OS in patients with relapsed FL, especially in patients receiving less than 3 CT regimen, highlighting the importance of completing the HSCT earlier, during the disease’s chemosensitive phase. Our data suggest the curative potential of HSCT in these patients, due to the GVL effect in allogeneic HSCT and/or intensive high-dose CT in autologous HSCT. More studies are needed to validate these observations. Disclosures No relevant conflicts of interest to declare.

Rituximab Plus Hypercvad (R-HCVAD) Alternating with Rituximab Plus High-Dose Methotrexate-Cytarabine (R-M/A) in Untreated Mantle Cell Lymphoma (MCL): Prolonged Follow-Up Confirms High Rates of Failure-Free Survival (FFS) and Overall Survival (OS).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 128-128 ◽  
Author(s):  
Jorge Enrique Romaguera ◽  
Luis Fayad ◽  
Maria A. Rodriguez ◽  
Fredrick B. Hagemeister ◽  
Barbara Pro ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Complete Remission ◽  
Stem Cell Transplant ◽  
Pulmonary Hemorrhage ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Hematologic Toxicity ◽  
Cell Transplant

Abstract Introduction: Aggressive MCL has a poor prognosis with a 21-40% complete remission (CR) after CHOP and a duration of response of only 10-16 months. More intense therapy could improve these statistics. Rituximab is effective in MCL and has minimal toxicity. Methods: A prospective phase II trial of R-HCVAD (considered to be one cycle) alternating every 21 days with R- M/A (considered to be another cycle) as described earlier (Ann Oncol. 13, suppl 2, 2002 #24). Prophylaxis with mesna, calcium leucovorin, prednisone eyedrops, G-CSF, antibacterial, antifungal, and antiviral therapy. CBC with differential and platelet counts X 2-3/week. Re-staging every 2 cycles including upper and lower endoscopies. Patients in complete remission (CR) after 6 courses of a planned 6-8 cycles were not offered consolidation with stem cell transplant. Post-treatment evaluation was performed every 3 months for 1 yr, every 4 months for 2 yrs, every 6 months for 2 years, then annually. Results: Of 100 patients registered, one was ineligible and two decided to not receive the treatment after registration, leaving 97 evaluable for analysis of response, survival and toxicity. An analysis of response after the first 6 cycles shows an 87% CR/CRu rate. With a median follow up of 40 months, the 3-year FFS and overall survival (OS) were 67% and 81%, respectively. Adverse factors for FFS were: Grade 4 hematologic toxicity was significant. Five patients died during treatment of sepsis (3), pulmonary hemorrhage (1), and unknown cause (1). Four patients developed myelodysplasia/acute myelogenous leukemia after treatment and while in CR and three have died, for a total of 8 deaths in the study (8%). Conclusion: R-HCVAD alternating with R-M/A without stem cell transplant is an effective regimen for treatment of aggressive untreated MCL, specially for patients ≤ 65 years old. Toxicity is as expected for an intense regimen. This encouraging data warrants continued follow-up and comparison with existing/new therapies in future trials.

Herpes Zoster (HZ) Infection in the Post-Hematopoietic Stem Cell Transplant Pediatric Population May Be Preceded by Transaminitis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3167-3167
Author(s):  
Jason N. Berman ◽  
Winter Berry ◽  
Molin Wang ◽  
Donna S. Neuberg ◽  
Eva C. Guinan
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Hematopoietic Stem Cell ◽  
Pediatric Population ◽  
Myelogenous Leukemia ◽  
Cell Transplant ◽  
Surprising Result ◽  
Skin Involvement ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct

Abstract HZ infection is a common complication following hematopoietic stem cell transplantation (HSCT). We reviewed the incidence, complications, and associated risk factors in a post-HSCT pediatric population at a single center and examined whether antecedent blood counts or transaminase levels (AST, ALT) might predict the onset of infection prior to the development of skin manifestations. Seventy-eight children between the ages of 2 months and 21 years developed HZ among the 309 patients, on whom data was available, who underwent HSCT from January 1995 to December 2002. Underlying diagnoses included: acute leukemia (n=108), chronic myelogenous leukemia (n=22), myelodysplastic syndrome (n=24) and other conditions (n=155). Two hundred patients underwent an allogeneic HSCT (98 sibling donor, 102 unrelated donor) and 109 underwent an autologous HSCT. The incidence of HZ was 25% by 10 months and 40% by 70 months post-HSCT. Post-herpetic neuralgia occurred in 21/73 (29%; 95% CI=19%, 41%) evaluable patients, disseminated skin involvement in 15/74 (20%; 95% CI= 12%, 31%) patients and visceral organ involvement in 6/75 (8%; 95% CI= 3%, 17%) patients. Acyclovir prophylaxis for cytomegalovirus (CMV) antigen positivity was given for 21 days post-BMT in 49/75 (65%) patients and had no impact on the incidence or onset of HZ, nor did immune compromise (defined as history of chemotherapy or underlying primary immune deficiency) prior to HSCT. Risk factors for development of HZ included: patient age-greater than 10 years (p&lt;0.0001), allogeneic HSCT (p&lt;0.001), and conditioning with total body irradiation (TBI) (p&lt;0.059). Type of allogeneic donor did not add significantly to the model. Graft-versus-host-disease (GVHD) increased the interval to HZ infection (p&lt;0.0018). There was insufficient evidence to attribute this surprising result to CMV prophylaxis. However, prior GVHD did increase the risk of disseminated skin involvement (p&lt;0.016). There was a significant change in ALT level in the month preceding diagnosis of HZ (p&lt;0.02), with 22/37 (59%) evaluable patients having a progressive increase. This rise in ALT level was not associated with GVHD (p=0.60). Changes in AST levels, white blood cell and platelet counts were not significant. Forty-four patients were admitted to hospital for HZ infection for a median of 6 days (range 2–39). Length of stay for allogeneic patients was significantly affected by skin dissemination and visceral involvement (p&lt;0.023 and p&lt;0.034, respectively) and not by donor type, prior immune status, GVHD or TBI. Inclusion of HZ infection post-HSCT in the differential diagnosis of patients with a rising ALT level, particularly if &gt; 10 years of age after allogeneic HSCT with TBI conditioning may allow for earlier initiation of therapy with less morbidity and decreased need for hospital admission.

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