Allogeneic Hematopoietic Stem Cell Transplantation with Nonmyeloablative Conditioning in Patients with Myeloid Leukemias: Results of a Prospective Study of the Latin American Cooperative Onco Hematology Group (LACOHG).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5154-5154
Author(s):  
Guillermo J. Ruiz-Arguelles ◽  
David Gómez-Almaguer ◽  
José D. Gómez-Rangel ◽  
Jorge Vela-Ojeda ◽  
Amado Kardus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Latin American ◽  
Myelogenous Leukemia ◽  
Allogeneic Bone ◽  
Transplant Survival ◽  
Post Transplant

Abstract Using a nonmyeloablative stem cell transplantation (NST) program previously shown to be effective in individuals receiving allografts in México, 29 patients with either acute myelogenous leukemia (AML, n = 12) or chronic myeloid leukemia (CML, n = 17) from the Latin American Cooperative Onco Hematology Group (LACOHG) were prospectively given allogeneic bone marrow allografts. Patients received a modified NST conditioning regimen consisting of oral busulphan 4 mg/kg on Days −6 and −5, IV cyclophosphamide 350 mg/m2 on Days −4, −3, and −2, IV fludarabine 30 mg/m2 on Days −4, −3, and −2, oral cyclosporine A 5 mg/kg twice daily starting on Day −1 (continuing until Day 180), and IV methotrexate 5 mg/m2 on Days +1, +3, +5, and +11. Median patient age was 43 years (range, 10–63). All patients engrafted; median time to achieve an absolute neutrophil count >0.5 x 109/L was 14 days (range, 0–21), whereas the median time to achieve a platelet count >20 x 109/L was 12 days (range, 0–21). Follow-up periods ranged between 39 and 519 days (median, 249). In patients with CML, the median overall post-transplant survival has not been reached, whereas the 519-day overall survival was 88%, and the 100-day mortality was 0%. In patients with AML, the median overall post-transplant survival has not been reached, the 459-day overall survival was 66%, and the 100-day mortality was 8%. The results from this multicenter, multinational study complement and further support the efficacy of our NST preparative regimen. The initial experience obtained from individuals with CML and AML receiving allografts in 2 institutions in México has now been extended into other Latin American countries, and the results are acceptable.

The Early Referral for Reduced-Intensity Stem Cell Transplantation in Patients with Ph1 (+) Chronic Myelogenous Leukemia in Chronic Phase in the Imatinib Era: Results of the Latin American Cooperative Oncohematology Group (LACOHG) Prospective, Multicenter Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4838-4838
Author(s):  
Guillermo J. Ruiz-Arguelles ◽  
David Gomez-Almaguer ◽  
Amelia Morales-Toquero ◽  
Cesar H. Gutierrez-Aguirre ◽  
Jorge Vela-Ojeda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Chronic Myelogenous Leukemia ◽  
Latin American ◽  
Chronic Gvhd ◽  
Chronic Phase ◽  
Myelogenous Leukemia ◽  
Reduced Intensity

Abstract Using a reduced intensity stem cell transplantation (RIST) schedule, 24 patients with Ph1 (+) chronic myelogenous leukemia (CML) in first chronic phase were prospectively allografted in four Latin American countries: Mexico, Brasil, Colombia and Venezuela, using HLA-identical siblings as donors. Median age of the patients was 41 years (range 10 to 71); there were 8 females. Patients received a median of 4.4 x 106/ Kg CD34 cells. Median time to achieve above 0.5 x 109/L granulocytes was 12 days, range 0–41, whereas median time to achieve above 20 x 109/L platelets was also 12 days, range 0–45. Twenty two patients are alive 81 to 830 (median 497) days after the RIST. The 830-day probability of survival is 92%, whereas median survival has not been reached, being above 830 days. Eleven patients (46%) developed acute graft versus-host disease (GVHD), whereas 7 of 23 (30%) developed chronic GVHD. Two patients died 43 and 210 days after the RIST, one as a result of sepsis and the other one of chronic GVHD. The 100-day mortality was 4.4 %, whereas the transplant-related mortality was 8%. RIST for patients with CML in chronic phase seems as an adequate therapeutic option.

scholarly journals Outcome of Autologous Stem Cell Transplantation in Myeloma Patients Aged ≥ 75 Years

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3453-3453 ◽  
Author(s):  
Qaiser Bashir ◽  
Mohammed El Shazly ◽  
Denái R. Milton ◽  
Krina Patel ◽  
Nina Shah ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Response Rate ◽  
Progression Free Survival ◽  
Free Survival ◽  
Post Transplant

Abstract Introduction Multiple myeloma (MM) is a disease of elderly with median age of diagnosis 66-years. Autologous hematopoietic stem cell transplantation (auto-HCT) is recommended for eligible patients with newly diagnosed MM, however, it is not offered to many elderly patients due to concerns of excessive toxicity. We have previously reported that auto-HCT can be safely performed in myeloma patients aged ≥ 70 years (Bashir et al. L&L 2012). Here we report the results of a retrospective analysis of MM patients aged ≥ 75 years who underwent auto-HCT at our center. Methods All myeloma patients aged ≥ 75 years who underwent auto-HCT at our institution between 1/1/2000 and 12/31/2015 were retrospectively analyzed. Frequencies of toxicities were compared using Fisher's exact test. The cumulative incidence (CI) of non-relapse mortality (NRM) was assessed using the competing risks method. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Differences in survival between groups were assessed using the log-rank test. The association between survival and patient subgroups of interest was determined using univariate and multivariable Cox proportional hazards regression models. Results 72 patients (median age 76 years; 58% male) were included in the study. Thirty percent (n=19/63) were ISS stage I, 43% (n=27/63) were stage II and 27% (n=17/63) stage III. Seventy-eight percent (n=56) were considered standard-risk (IMWG criteria) and 22% (n=16) had high-risk cytogenetics. Sixty-three percent (n=45) received conditioning with melphalan (MEL) 140 mg/m2, while 38% (n=27) received MEL >140. Seventy-five percent (n=54) of the patients received auto-HCT as part of first line therapy and 85% (n=61) had at least partial response (PR) at auto-HCT. Median time from diagnosis to auto-HCT was 7.6 months. Half of the patients (n=36) received post transplant maintenance. Median follow-up time for all survivors (n=48) was 25.5 months. Grade II-IV toxicity was seen in 74% (n=53) of patients, gastrointestinal being most common (49% of all patients). There was no difference in toxicity between MEL 140 vs. MEL >140. The median time to neutrophil and platelet engraftment was 11 and 12 days, respectively. The CI of NRM was 1% at Day 100 and 6 months and 4% at the end of the assessment period. Day 100 response rate (at least PR) was 92% (n=66), with 36% (n=26) achieving near complete remission (nCR) or better. Median PFS was 31.4 months (95% CI: 22.6, 36.6, Figure 1). Seventy-five percent of the patients were event free at one year after transplant and 23% were event free at 5 years. Median OS was 72.8 months (95% CI: 45.7, 86.2, Figure 2). The OS rates at 1 year and 5 years post transplant were 93% and 58%, respectively. On multivariable analysis, high-risk cytogenetics and ISS stage III disease were associated with significantly worse PFS and OS. Conclusion Auto-HCT in myeloma patients aged ≥ 75 years is feasible with response rate and survival comparable to that seen in younger patients. Age alone should not be used to determine eligibility for auto-HCT. Figure 1 Progression-free survival (all patients). Figure 1. Progression-free survival (all patients). Figure 2 Overall survival (all patients). Figure 2. Overall survival (all patients). Disclosures Ciurea: Cyto-Sen Therapeutics: Equity Ownership; Spectrum Pharmaceuticals: Other: Advisory Board.

scholarly journals Outpatient-Based Haploidentical Stem Cell Transplantation Using Post-Transplant Cyclophosphamide is Feasible. Experience in a Single Latin-American Center

2018 ◽  
Vol 24 (3) ◽  
pp. S407-S408
Author(s):  
David Gómez-Almaguer ◽  
Perla R. Colunga-Pedraza ◽  
Andrés Gómez-De León ◽  
Julia E. Colunga-Pedraza ◽  
Guillermo Sotomayor-Duque ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Latin American ◽  
Post Transplant ◽  
Haploidentical Stem Cell Transplantation

scholarly journals Survival in Patients Who Underwent HLA-Haploidentical Stem Cell Transplantation in Two Centers in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Lisbeth Ramirez ◽  
Juan Manuel Herrera ◽  
Angela María Peña ◽  
Maria Luna-Gonzalez ◽  
Claudia Marcela Chalela ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Clinical Characteristics ◽  
High Dose ◽  
Post Transplantation ◽  
Hematopoietic Stem

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for several malignant and non-malignant hematological diseases. However, sometimes it is challenging to find human leukocyte antigen (HLA)-matched related or unrelated donors, especially in minority populations such as Hispanics. Transplantation of T cell replete HLA haploidentical graft (HaploHCT) followed by a high dose post-transplantation cyclophosphamide (PTCy) to eradicate alloreactive T cells is an option for populations with low donor availability. HaploHCT has emerged as an effective and safe strategy in this population (Luznik L et al. BBMT 2008), but data in Hispanics is scarce. Objective: The aim of our study was to describe the clinical characteristics and assess overall survival at 100 days, 1- and 3-years of patients who underwent haploHCT in two Colombian reference centers. Methods: An observational retrospective study was conducted at two tertiary referral centers in Colombia. Patients who underwent haploHCT at Clinica FOSCAL and Centro Medico Imbanaco between January 2013 and January 2020 were selected. Demographic and clinical characteristics where analyzed using descriptive statistics. The Kaplan-Meier method was used to assess overall survival (OS) rates and the log-rank test was used to compare survival rates between groups. All data were analyzed using R statistical software®. Results: Seventy-six patients were included. Mean age at transplantation was 34 years (range 18-60). Forty-two (57.89%) patients were female. Average body mass index was 19.86kg/m2. The majority of patients (57%) had a pre-transplantation ECOG performance status of 2. The most common indication for haploHCT was acute lymphoblastic leukemia (55.26%), followed by acute myeloid leukemia (23.64%). A sibling was the donor in 69.74% of the cases. Forty-seven (61.84%) patients were ABO-matched group. Peripheral blood stem cells were the graft source in 96% of the patients. The average number of infused CD34+ cells was 11.15 x 106/kg. Fludarabine-melphalan was the most commonly used conditioning regimen (57%), followed by fludarabine-busulfan-thiotepa (39%). Graft-versus-host disease (GVHD) prophylaxis consisted of PTCy (50 mg/kg/day) on days 3 and 4 after HCT and a calcineurin inhibitor plus mycophenolate mofetil from day 5 to day 35 post-HCT. Median time to neutrophil engraftment (neutrophils > 0,5x109/L) was 15 days (range 10-33), while platelet engraftment, defined as as the second day of unsupported platelet count of ≥20 × 109, occurred at a median time of 13 days (range 5-38) post-transplantation. On day 28 post-HSCT, 93.4% of the patients had achieved 100% chimerism. OS was 91% (95%CI 84-97.5) at 100 days, 81% (95%CI 72-90) at 1-year, and 77% (95%CI 68-88) at 3-years after HaploHCT. C onclusion: The results of our haploHCT retrospective study in a Hispanic population are comparable to several other cohorts that have reported similar outcomes of haploHCT compared to HLA-matched HCT. The OS rates reported in our study suggest that haploHCT is a viable option in patients without an HLA-matched related or unrelated donor available, especially in populations with lower rates of suitable donors. Acknowledgements: We deeply thank Gonzalo Gutiérrez García, M.D. for his leadership and guidance implementing the haploHCT program in Clinica FOSCAL. Disclosures Peña: Roche: Honoraria. Salazar:Janssen: Honoraria; Novartis: Honoraria. Sandoval-Sus:MorphoSys US: Consultancy; Janssen: Consultancy; Massive Bio: Consultancy; Celgene: Speakers Bureau. Sossa:Novo: Honoraria; Takeda: Honoraria; Astellas: Honoraria; Roche: Honoraria.

Pre-Transplant Rituximab Therapy Is Associated with Improved Progression-Free and Overall Survival in Patients Undergoing Autologous Hematopoietic Stem Cell Transplantation for Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 19-19 ◽  
Author(s):  
Timothy S. Fenske ◽  
Parameswaran Hari ◽  
Jeanette Carreras ◽  
Mei-Jie Zhang ◽  
Rammurti Kamble ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
B Cell Lymphoma ◽  
Hematopoietic Stem ◽  
Post Transplant ◽  
Conditioning Therapy

Abstract Outcomes following first-line therapy for patients (pts) with DLBCL have improved significantly with the availability of the chimeric anti-CD20 monoclonal antibody rituximab (R). Despite this progress, many pts develop refractory or recurrent DLBCL and are considered candidates for autologous hematopoietic stem cell transplantation (AuHCT). For such pts, it is possible that R given pre-transplant and/or during conditioning therapy affects the natural history of DLBCL, such that traditional methods of risk assessment and patient selection for AuHCT may need revision. We therefore studied the outcomes of 1,006 pts who underwent peripheral blood AuHCT for DLBCL between 1996 and 2003 reported to the CIBMTR, analyzed according to whether R was (n=188, “+R” group) or was not (n=818, “-R” group) administered prior to AuHCT. Using the chi-square statistic for categorical and the Kruskal-Wallis for continuous variables, there were no significant differences between the +R and -R groups with regard to gender, pre-transplant performance status, disease status at transplant, pre-transplant chemosensitivity, second-line aa-IPI score distribution, Ann Arbor stage at transplant, interval from diagnosis to transplant, bulky disease, bone marrow involvement, post-transplant radiation therapy, or post-transplant myeloid growth factor therapy. The +R group had a higher proportion of pts age 61 or older (40% vs. 23%, p<0.001). AuHCT occurred between 1999–2003 in 96% of pts in the +R group, and between 1996–2001 in 93% of the -R pts (p<0.001). For the +R pts, 94% received R only with pretransplant chemotherapy, 3% only with conditioning therapy, and 3% with both pretransplant chemotherapy and conditioning therapy. Conditioning regimens were similar in the +R and -R groups, with the majority receiving the BEAM regimen. In univariate analysis, platelet and neutrophil engraftment were not affected by use of R. Treatment-related mortality (TRM) at 1, 3, or 5 years did not differ significantly between the +R and -R groups. Progression-free survival (PFS) at 1 and 3 years was superior in the +R group (62% vs. 49% at 1 year, p=0.002; 49% vs. 38% at 3 years, p=0.010). Overall survival (OS) was superior in the +R group (68% vs. 60% at 1 year, p=0.032; 57% vs. 45% at 3 years, p=0.003). In multivariate analysis, later year of transplant (2000–2003) and age <55 were associated with lower TRM, but pre-transplant R was not. Conversely, pre-transplant R, age <55, and fewer than 3 lines of chemotherapy were associated with improved PFS, while year of transplant was not. Finally, pre-transplant R, age <55, fewer than 3 lines of chemotherapy, and year of transplant 2000–2003, were all associated with improved OS. We conclude that pre-transplant rituximab is associated with improved PFS and OS following AuHCT for DLBCL, with no evidence of impaired engraftment or increased TRM.

Impact of Allogeneic Stem Cell Transplantation as Salvage Therapy After T315I Mutation Detection in Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL) Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 645-645
Author(s):  
Franck Emmanuel Nicolini ◽  
Wei Zhou ◽  
Giovanni Martinelli ◽  
Michael J. Mauro ◽  
Andreas Hochhaus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Mutation Detection ◽  
Treatment Start ◽  
T315i Mutation ◽  
Tki Treatment

Abstract Abstract 645 Background: The development of a BCR-ABL T315I mutation is associated with a poor prognosis and limited therapeutic options. The impact of the mutation on the outcome of stem cell transplantation (SCT) is unknown. Aim: To describe the overall survival (OS) of CML patients in any phase and Ph+ ALL patients who received an allogeneic SCT after developing a T315I mutation after exposure to tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective, multi-center observational study of 222 CML and de novo Ph+ ALL patients who developed a T315I mutation between 1999 and 2008. Data from the medical records of 33 patients (15% of all patients in the registry) from 9 countries (USA, France, Italy, Germany, Denmark, Singapore, and the UK) who received an allogeneic SCT after T315I mutation detection were included in this study. Results: At the time of diagnosis, the median age was 39 years (range, 16-67); 70% were male; 26 patients were in CML CP, 1 in CML AP, 2 in CML BC, and 4 had Ph+ ALL. The median time between diagnosis and TKI treatment start was 3 months (range, 0-125), between diagnosis and T315I mutation detection was 28 months (range, 3-131), and between TKI treatment start and T315I mutation detection was 19 months (range, 2-64). Five (15%) patients had TKIs as frontline therapy. At the time of T315I detection, 10 patients were in CML CP, 7 in CML AP, 12 in CML BC, and 4 had Ph+ ALL. Hydroxyurea (alone or combined with other treatments) was the most common 1st line treatment (55%) after T315I mutation detection. The median time from T315I mutation detection to SCT was 3 months (range, 0.3-28). At the time of transplant, the median age was 42 years (range, 22-68); 8 patients were in CML CP, 7 in CML AP, 14 in CML BC and 4 had Ph+ ALL; 32 patients received 1 SCT and 1 received 2 SCTs after T315I mutation detection. The source of stem cells was peripheral blood (53%), bone marrow (35%), cord blood (6%), and unknown (6%). 82% were matched donor and 18% were unmatched. The median follow-up time from SCT was 7 months and 15 (55%) patients had died by their last follow-up. The OS of CML CP and CML AP patients was much better than CML BP and Ph+ ALL patients (Fig. 1; logrank, p=.050). The 1-yr OS rates (95% CI) from SCT were 69% (21-91%) for CML CP, 71% (26-92%) for CML AP, 16% (3-39%) for CML BC, and 33% (1-77%) for Ph+ ALL; and the 3-yr OS rates (range) was 69% (21-91%) for CML CP, 71% (26-92%) for CML AP, 0 for CML BC, and 0 for Ph+ ALL. Conclusion: These results suggest that the survival of patients harboring a T315I mutation and treated with allogeneic SCT is dependent on the disease phase at the time of SCT. SCT is the treatment of choice for these CML patients, particularly those in CP and AP.Fig. 1.Overall survival from Allogeneic SCTFig. 1. Overall survival from Allogeneic SCT Disclosures: No relevant conflicts of interest to declare.

High Dose (HD-AraC) Vs Standard Dose Cytosine Arabinoside (SD-AraC) During Induction and IL-2 Vs Observation After Consolidation/Autologous Stem Cell Transplantation in Patients with Acute Myelogenous Leukemia (AML): Final Report of the AML-12 Trial of EORTC and GIMEMA Leukemia Groups on the Value of High Dose AraC

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 257-257 ◽  
Author(s):  
Roelof Willemze ◽  
Stefan Suciu ◽  
Franco Mandelli ◽  
Giovanna Meloni ◽  
Boris Labar ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Myelogenous Leukemia ◽  
Phase Iii ◽  
High Dose ◽  
Treatment Difference

Abstract Abstract 257 The AML-12 randomized phase III trial of EORTC-LG and GIMEMA assessed the efficacy and toxicity of HD-AraC (3 g/sqm/12 hrs for 4 days) combined with daunorubicin (50 mg/sqm/d for 3 days) and etoposide (50 mg/sqm/d for 5 days) vs SD-AraC (100 mg/sqm/d for 10 days) with the same drugs, in previously untreated AML < 61 year old patients (APL excluded). Patients (pts) in complete remission (CR) had to receive consolidation consisting of AraC (500 mg/sqm/12 hrs for 6 days) and daunorubicin. Subsequently an allogeneic (allo-SCT) or autologous stem cell transplantation (auto-SCT) was planned according to donor availability and age. A 2nd randomization had to be done after evaluation of consolidation in pts without a donor: auto-SCT followed or not by low dose IL-2. The aim of the trial was to detect an 8% treatment difference (from 35% to 43%) in the 5-yr overall survival (OS) rate, corresponding to a hazard ratio (HR) of 0.80 (alpha=5%, power=95%); secondary endpoints were response to induction, toxicity, disease-free survival (DFS) from CR. Randomization was performed centrally; the 1st randomization was stratified for age (<46 vs > 45 yrs), performance status, WBC and center. Intent-to-treat analysis was done. From 9/1999 till 1/2008, 2005 pts from 68 centers were randomized. Due to insufficient reporting, 3 centers, who recruited 63 patients, have been excluded from the analysis. The remaining 1942 pts (872 pts entered by EORTC-LG and 1070 by GIMEMA) 969 were randomized in SD-AraC and 973 in HD-AraC arm; among them 25 and 28, respectively, were ineligible, but kept in the analysis. Both arms were comparable with respect to gender, age (median=45 yrs), disease history, initial leukocyte count, PS, FAB and cytogenetics. At a median follow up of 6 yrs, 1114 pts had died. Results: After 1 or 2 courses of induction, CR was achieved in 1430 pts (73.6%); 684 (71.9%) pts (SD-AraC group) vrs 746 (78.7%) pts (HD-AraC group): p=0.002. Resistance was documented in 173 (18.2%) vrs 123 (13%), and death during induction in 85 (8.9%) vrs 71 (7.5%) pts, respectively. Induction toxicity profile and grade was similar in the 2 arms except for conjunctivitis grade 3: HD-AraC>SD-AraC. CR rates for pts<46 yrs were 74.7% (SD-AraC) and 81.4% (HD-AraC) and for pts>45 yrs 66.4% (SD-AraC) and 71.8% (HD-AraC). 634 pts (SD-AraC and 686 (HD-AraC) received a consolidation cycle. Among 765 CR-pts<46 yrs 284 pts had an HLA identical sibling (<46D) and 481 did not or had not been typed (<46NoD). Among 665 CR-pts>45 yrs 225 pts had an HLA identical sibling (>45D) and 440 did not or had not been typed (>45NoD). In the <46D group 211 underwent an allo-SCT and 11 an auto-SCT. In the <46NoD group 274 underwent an auto-SCT and 29 a MUD-SCT; in the >45D group 147 underwent an allo-SCT and 14 an auto-SCT. In the >45NoD group 244 underwent an auto-SCT and 12 a MUD-SCT. Comparisons of treatments arm regarding OS from randomization, DFS and Survival (S) from CR are indicated in the Table. The impact of age on the treatment difference regarding OS was almost significant (p=0.06). In pts >45 who reached CR, the decrease in the relapse rate in the HD-Ara-C arm vrs SD-Ara-C arm (45.5% vs 49.4%) was counterbalanced by an increase in the death in CR rate (18.4% vs 13.2%). Conclusion: The final evaluation of the EORTC-GIMEMA AML-12 trial shows that, with a median follow-up of 6 years, HD-AraC in the induction treatment leads to a significantly higher CR rate than SD-Ara-C and results in improvement in overall survival but only in pts under the age of 46 years. Disclosures: Muus: Amgen: Membership on an entity's Board of Directors or advisory committees. Beksac:Janssen Cilag: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau.

Third Autologous Stem Cell Transplantation for Relapsed Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4548-4548
Author(s):  
Catherine Garnett ◽  
Chrissy Giles ◽  
Maialen Lasa ◽  
Osman Ahmed ◽  
Marco Bua ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant

Abstract Abstract 4548 High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is currently standard treatment for younger patients with multiple myeloma (MM). In the face of almost inevitable disease relapse, there is growing evidence for second ASCT as salvage therapy in certain patient groups. However, few published data exist regarding efficacy and safety of third ASCT in relapsed disease. We retrospectively analysed the results of eight patients treated at a single UK institution who each received three separate autologous stem cell transplants for relapsed MM between May 1997 and April 2012. There were four men and four women. Median age at diagnosis was 48 years (range, 25–64 years). Paraprotein isotype was IgA in two patients and IgG in the remaining six patients. At the time of 1st transplant, seven patients were in partial response (PR) and one in complete response (CR). Conditioning melphalan dose was 200mg/m2 in all but two patients who received 140mg/m2. Three patients entered CR following 1st transplant and four patients showed PR. Median time to disease progression was 31 months (range, 11.8–52.9 months). Prior to 2nd transplant, five patients achieved very good partial response (VGPR) and three PR with induction chemotherapy. Melphalan dose was 200mg/m2 in five patients and 140mg/m2 in the remaining three. Median time to disease progression was 22.3 months (range, 10.1– 39.6 months). At the time of 3rd transplant, two patients had achieved VGPR following induction chemotherapy, one showed PR, two stable disease (SD) and three evidence of disease progression. For the 3rd transplant, melphalan dose was reduced in most cases. Median follow up post 3rd transplant was 8.3 months (range 1.1–29.3 months). One patient died of overwhelming sepsis within one month of transplantation (treatment related mortality). At the time of analysis, five patients had relapsed following 3rd ASCT, with median time to disease progression of 10.4 months (range, 2.7–23.7 months). Three of these patients died at 3.5, 17.6 and 27.1 months post 3rd transplant. The remaining two patients are alive with no evidence of disease relapse (progression free survival (PFS) time of 3.3 and 1.3 months). Overall survival (OS) for the group from diagnosis is 62% at 10 years with a median OS from diagnosis of 149 months (range 68.5 – 189.2 months) (Figure 1). Median OS for the group from 3rd transplant is 17.6 months (range, 1.1–29.3 months) (Figure 2). Median PFS is 10.4 months (range 1.1–23.7 months). These results demonstrate that third ASCT is a possible treatment strategy for patients with relapsed MM and may prolong patient survival. Figure 1: Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 1:. Overall survival from diagnosis for patients receiving 3rd autologous stem cell transplantation for relapsed multiple myeloma Figure 2: Overall survival from time of 3rd autologous stem cell transplant Figure 2:. Overall survival from time of 3rd autologous stem cell transplant Disclosures: No relevant conflicts of interest to declare.

Predominant Reconstitution of B Lymphoid Precursors (hematogones) Following Cord Blood Stem Cell Transplantation Is Associated with Less Occurrence of Acute Graft-Versus-Host Disease and Superior Overall Survival.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2231-2231
Author(s):  
Takahiro Shima ◽  
Toshihiro Miyamoto ◽  
Yoshikane Kikushige ◽  
Kenjirou Kamezaki ◽  
Katsuto Takenaka ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
B Cells ◽  
Stem Cell Transplantation ◽  
B Cell ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Myelogenous Leukemia ◽  
Cord Blood Stem Cell ◽  
B Cell Precursors

Abstract Abstract 2231 Poster Board II-208 Primary B cell development from hematopoietic stem cells occurs in the bone marrow (BM). During their development, B cell precursors progress through a series of distinct developmental stages; early-B cells, pro-B cells, and pre-B cells. The number of these B cell precursors is gradually declined with aging. Benign B cell precursors, originally termed hematogones (HG), can be observed in the BM during hematopoietic recovery phase in some patients who received chemotherapy or allogeneic bone marrow transplantation (allo-BMT). However, little is known about HG following cord blood stem cell transplantation (CBT). We retrospectively analyzed populations of B cell precursors of BM samples from 115 patients who received allogeneic stem cell transplantation (SCT). Patients included 49 women and 66 men, with a median age of 49 years (19-66 years). The underlying diseases of 115 patients varied; 43 acute myelogenous leukemia, 18 acute lymphocytic leukemia, 4 chronic myelogenous leukemia, 15 myelodysplastic syndrome, 17 malignant lymphoma, and 18 others. 65 patients underwent allo-BMT and 50 underwent CBT. Mean number of the infused cells amounted of 2.80 × 108 cells/kg (0.92-4.02 × 108) for allo-BMT and 2.78 × 107 cells/kg (1.77-5.00 × 107) for CBT. 68 patients received myeloablative conditioning regimen and 47 received reduced intensity conditioning regimen. GVHD prophylaxis included 3 cyclosporine (CSP) alone, 16 CSP and mycophenolate mofetil, 33 CSP and methotrexate (MTX), 5 tacrolimus (Tc) alone, and 58 Tc and MTX. Median time between day 0 of SCT and days performed on evaluation of HG by BM aspiration was 38 days (14-140 days). At that time, engraftment of donor cells was confirmed by chimerism analysis, indicating HG were proven to be donor-origins. HG were detected averagely in 1.56% of BM cells (0.01-12.27%) for allo-BMT recipients and 7.04% (0.03-55.56%) for CBT recipients, respectively. These results indicated CBT recipients presented much higher frequency and prominent reconstitution of HG compared to allo-BMT recipients (p<0.001, Figure 1). We next analyzed the proportion of HG by comparing donors' age with recipients' age, since B lymphopoiesis is associated with aging under the physiologically condition. Donor's age for CBT was defined as 0 year for analyses. Median age of donor was 37 years (17-66 years). Frequency of HG following SCT significantly declined with increasing the donors' age (p<0.001), but not the recipients' age. Furthermore, episode of acute GVHD presented statistically significant low frequency of HG (p<0.01), whereas chronic GVHD did not. In addition, there was no relationship between the percentage of HG and underlying disease, infectious complications, conditioning regimen. We also analyzed the relationship between HG and overall survival (OS). The existence of HG was defined as the percentage of HG greater than 1% in the BM. Appearance of HG was closely associated with superior OS at 3 years in both allo-BMT and CBT recipients (OS at 3-years, 84% in HG+ BMT pts vs 52% in HG- pts, p<0.05; OS at 3-years, 65% in HG+ CBT pts vs 7% in HG- pts, p<0.001, respectively, Figure 2). In conclusion, predominant reconstitution of HG can be detected following CBT higher than allo-BMT, indicating reconstitution of HG depends on donor's age rather than recipient's age. These findings suggest primary lymphoid development may depend on the intrinsic property of stem cells and progenitors, especially aging, rather than BM microenvironments. Furthermore, appearance of HG might be associated with less occurrence of acute GVHD and superior overall survival. For patients who undergo SCT, HG often can be confused with relapse of their disease. Our study indicated prudent attention should be taken in CBT as well as BMT recipients, and HG might reflect favorable progress in SCT recipients, although clinical significance of expanded HG has not yet been resolved. Disclosures: No relevant conflicts of interest to declare.

Unmanipulated HLA-Haploidentical (2-3 antigen-mismatched) Stem Cell Transplantation Using Myeloablative or Reduced-Intensity Preconditioning Regimen,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4117-4117 ◽  
Author(s):  
Katsuji Kaida ◽  
Kazuhiro Ikegame ◽  
Satoshi Yoshihara ◽  
Kyoko Taniguchi ◽  
Shinichi Ishii ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Acute Gvhd ◽  
Disease Status ◽  
Gvhd Prophylaxis ◽  
Refractory Diseases ◽  
Reduced Intensity

Abstract Abstract 4117 Related haploidentical donors, as cord blood, can be alternative donor sources in stem cell transplantation (SCT). Severe GVHD, however, has interfered the progress of haploidentical SCT (haploSCT). To deal with this strong GVHD, T cell depletion has usually been used in US and European countries. In order to pursue the controllable GVL effect by T cells, we have performed unmanipulated haploSCT using myeloablative or reduced intensity preconditioning regimen accompanied with intensified GVHD prophylaxis, including steroids. In this meeting, we will summarize our experience of haploSCT for more than ten years. From August 1998 to September 2010, we have performed 351 cases of haploSCT (all cases were HLA 2–3 antigen mismatched in GVH direction). Patients' characteristics are sex: male 186, female 168, age: 16–65 years old (median 39), disease: AML/MDS 149, ALL 81, ML 67, others 54. Eighty-three percent of cases underwent SCT in non-complete remission (non-CR) status. Patients under 45 years old underwent myeloablative preconditioning regimen consisting of FLU/CA/CY/TBI 8Gy (haplo-full, n=100), and patients over 45 years old or with comorbidities or repetitive SCT (including second to fifth SCT) underwent reduced intensity preconditioning regimen consisting of FLU/(CA)/BU/ATG or FLU/(CA)/MEL/ATG (haplo-mini, n=251). High dose Ara-C (CA) was optional to reduce tumor burden. As ATG, ATG (Fresenius) 8mg/kg, or thymoglubulin (genzyme) 2–4mg/kg were integrated into conditioning treatments mainly for reduced-intensity transplantation. GVHD prophylaxis consisted of taclolimus (TAC), methylprednisolone (mPSL) 2mg/kg/day, short term MTX, and mycophenolate mofetil (MMF) 15mg/kg/day in haplo-full, and TAC, and mPSL 1mg/kg/day in haplo-mini, respectively. For elderly patients over 50 years old in haplo-mini, MMF was added. Hematopoietic engraftment in haploSCT was as rapid as that in HLA-identical SCT, except 10 cases of graft rejection. The median time to reach a neutrophil account of >0.5 × 109/l was 10 days for haplo-mini and 13 days for haplo-full. Platelet recovery was achieved in 66 % and 60% of patients undergoing haplo-mini and haplo-full, respectively. The median time to reach a nontransfused platelet count of 3 20 × 109/l was 22 days for haplo-mini and 33 days for haplo-full. Sixty percent of haplo-mini patients and 54 % of haplo-full patients did not develop acute GVHD. Acute GVHD (grade II-IV) was observed in 20% for haplo-mini and 36 % for haplo-full. Overall survival at five years was 30% for haplo-full and 40% for haplo-mini, respectively. If limited to CR cases, overall survival reached over 60% in haplo-mini. There is no difference in survival rate among patients' diseases. In multivariate analysis on survival using variables, including disease status before transplantation, haplo-full vs haplo-mini, mismatches in GVH direction, mismatches in HVG direction, patients' age, and the number of transplantation times, the disease status (CR) was found to be only a significantly favorable factor (P= 0.0026). Unmanipulated haploSCT is feasible and effective for refractory diseases. ATG dose used in haplo-mini is critical, and rather low compared with that of European cases reported so far. Although it should be too early to refer long term outcome, unmanipulated haploSCT could be considered as an option to control refractory diseases. Disclosures: No relevant conflicts of interest to declare.

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