Results of Second or Third Allogeneic Hematopoietic Cell Transplantation As Salvage Therapy for Patients Failing Primary Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4516-4516
Author(s):  
Birgit Federmann ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
Wolfgang A. Bethge
Keyword(s):  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Free Survival ◽  
Off Label ◽  
Allogeneic Hct ◽  
Pre Treatment

Abstract Abstract 4516 Introduction: Patients with relapse after allogeneic hematopoietic cell transplantation (HCT) have generally a very poor prognosis. Besides donor lymphocyte infusions, chemotherapy or supportive care, second or even third allogeneic HCT have been performed in selected patients. This is often associated with a high incidence of non-relapse-mortality (NRM) because of heavy pre-treatment or reduced performance status due to comorbidities or pre-treatment related complications. Method: We report a retrospective analysis of our single center experience with second or third allogeneic HCT between 2000–2011. We searched our database for patients receiving >1 allogeneic HCT in the past 10 years. Details on characteristics and clinical course of the patients were confirmed by retrospective chart review. Result: 47 patients received more than one allogeneic HCT (second HCT, n=44, second and third HCT, n=3). Median age of the patients was 40 (range, 18–65) years. 27 patients were male, 20 female. Diagnoses were acute myeloid leukemia (n=28), acute lymphoblastic leukemia (n=11), multiple myeloma (n=1), chronic myeloid leukemia (n=2), myelodysplastic syndrome (n=2), osteomyelofibrosis (n=2) and non-Hodgkin lymphoma (n=1). Reasons for second or third HCT were relapse (n=49) or primary graft failure (n=1). Median time between first and second HCT was 17 (range, 3–137) months, 12 months between second and third HCT (range, 10–16). For the first HCT 35 patients received myeloablative (MAC) and 12 reduced intensity conditioning (RIC). For the second HCT 16 patients received MAC and 31 RIC, for the third HCT RIC was used in all patients. 6/47 patients (13%) received salvage chemotherapy followed by RIC out of aplasia. Before salvage HCT disease status of the patients was CR=14, PR=33. Time to neutrophil engraftment after second and third HCT was 16 (range, 6–77) and 10 (range, 9–13) days, respectively; to platelet engraftment 16 (range, 9–71) and 23 (range, 14–73) days, respectively. 12 of 47 patients (26%) after second HCT are alive (CR=11, PR=1) and 1 of 3 patients is alive and in remission after receiving a third HCT. Kaplan-Meier estimated 3-year overall and event-free survival is 30% and 25%, respectively, with a median follow-up of 62 (range 6–111) months of patients alive. Outcome was better for patients in CR at HCT (3-year OS with 43% vs. 24%, p=0.13). In the subgroup of patients with acute leukemia 3-year OS and EFS was superior in patients with AML (32% and 31%) while all patients with ALL died. Older age had no negative impact on survival as 3-year OS in patients ≥40 years (n=25) was 43% compared to 15% in patients <40 years (n=22) (p=0.04). Cumulative incidence of NRM at 3 years with death due to relapse as competing risk after second HCT was 43%. 2 of 3 patients after third HCT died due to NRM. The use of RIC was associated with an inferior 3-year OS compared to MAC with 18% vs. 53%, p=0.08. Causes of death were relapse=18, infection=12, multiorgan failure=3, GVHD=1, EBV-LPD=1 and PML=2. Outcome was inferior if the second HCT was performed within 6 months after first HCT with a 3-year OS of 0% vs. 31%, p=0.02. In 8 patients the same donor as for primary HCT was used while in 39 patients an alternative donor (MRD=7, MUD=10, MMUD=7, MMRD=2, haplo=21) was chosen. Using the same donor seems to result in a better outcome with 3-year OS of 63% vs. 23%, p=0.08. Incidence of grade II-IV GVHD was 17%, of chronic GVHD 30%. Presence of cGVHD after second allogeneic HCT was associated with better survival (3-year OS 42% vs. 26%, p=0.31) especially after using RIC (33% vs. 11%, p=0.09) Conclusion: In view of the otherwise dismal prognosis of patients with relapse after allogeneic HCT, second or third allogeneic HCT is feasible and can achieve long term disease free survival in up to a third of patients, even in patients of more than 40 years of age. Thus, retreatment with allogeneic HCT appears to be the most promising salvage strategy besides DLI for relapse >6 months after allogeneic HCT. Disclosures: Off Label Use: The use of some agents in the conditioning is off-label.

scholarly journals Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia

2010 ◽  
Vol 28 (17) ◽  
pp. 2859-2867 ◽  
Author(s):  
Boglarka Gyurkocza ◽  
Rainer Storb ◽  
Barry E. Storer ◽  
Thomas R. Chauncey ◽  
Thoralf Lange ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct ◽  
Unrelated Donors ◽  
Acute Myeloid

PurposeAllogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients.Patients and MethodsTwo hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression.ResultsWith a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versus-host disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk.ConclusionAllogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.

Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia (CLL) with 17p Deletion: A Retrospective EBMT Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 47-47 ◽  
Author(s):  
Johannes Schetelig ◽  
Anja van Biezen ◽  
Dolores Caballero ◽  
Martino Rodrigo ◽  
Kari Remes ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Progressive Disease ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Median Interval

Abstract Purpose: Patients with advanced CLL and 17p deletion have a very poor prognosis even after intensive chemotherapy. While allogeneic hematopoietic cell transplantation (HCT) has the potential to cure patients with advanced CLL it is not known whether this holds true for patients with 17p deletion. Patients and Methods: Patients with 17p- CLL who had received HCT were identified by an EBMT-based survey. Baseline data were downloaded from the EBMT database. Additional information on the course of the disease, the cytogenetic diagnosis and last follow up was collected by a questionnaire. Data were analysed as of February 2007. Results: 56 patients were identified. Twelve patients with autologous HCT, haplo-identical donors or the detection of 17p- after HCT were excluded from further analysis. 44 patients had received an allogeneic HCT between March 1995 and July 2006 from a matched related donor (n=27) or unrelated volunteer donor (n=17). The median age at HCT was 54 years (range, 35 to 64 years). Until HCT the maximum stage had been Binet A or B in 37% of patients and Binet C in 61% of patients. The diagnosis of deletion 17p- was made by FISH in 82% and by conventional banding in 18% of patients. The median interval between first diagnosis and detection of 17p- was 2.3 years (range, 1 to 11 years) and the median interval between detection of 17p- and HCT was 0.5 years (range, 0 to 3 years). Patients had received a median of 3 chemotherapy regimens (range, 2 to 7 lines), including fludarabine in 93% of patients and alemtuzumab in 41% of patients. At HCT, 53% of patients were in remission while 47% of patients were in stable or progressive disease. Reduced intensity conditioning was applied in 89% of patients. Peripheral blood stem cells were transplanted in 93% of the patients. GVHD prophylaxis was performed heterogeneously. One patient experienced primary graft failure. Acute GVHD grades II to IV occurred in 44% of patients and extensive chronic GVHD in 46% of patients. After a median follow-up of 23 months (range, 2 to 90 months) of 26 patients who are alive, 18 were in complete remission, 4 in partial remission and 4 patients had progressive disease at last follow up. 4-year overall survival and progression-free survival was 48% (95% CI, 28% to 68%) and 37% (95% CI, 18% to 56%). The cumulative incidences of relapse and non-relapse mortality at 4 years were 36% and 27%. No late-relapse occurred in five patients with a follow-up of more than 4 years. Conclusion: Allogeneic HCT has the potential to induce long-term disease-free survival in selected patients with advanced 17p- CLL. Given the otherwise very dismal outcome of this disease, prospective studies on allogeneic HCT earlier in the course of 17p- CLL seem warranted.

The Effect of In Vivo T-Cell Depletion with Alemtuzumab on Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3014-3014
Author(s):  
Julio Delgado ◽  
Srinivas Pillai ◽  
Reuben Benjamin ◽  
Dolores Caballero ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Mixed Chimerism ◽  
Allogeneic Hct ◽  
Reduced Intensity

Abstract Reduced-intensity allogeneic hematopoietic cell transplantation (HCT) is increasingly considered as a therapeutic option for young patients with advanced chronic lymphocytic leukemia (CLL). We report 59 consecutive CLL patients who underwent allogeneic HCT following fludarabine and melphalan conditioning at four different institutions. For graft-versus-host disease (GVHD) prophylaxis, 38 patients (Cohort 1) received alemtuzumab (20–100 mg) and cyclosporine; and 21 patients (Cohort 2) received cyclosporine plus methotrexate or mycophenolate. Donors were 47 HLA-matched siblings and 12 unrelated volunteers, 6 of whom were mismatched. Median age at transplant was 53 (range, 34–64) years and median number of previous chemotherapy regimens was 3 (1–6), with 39% of patients being refractory to fludarabine. Nine patients had previously failed an autologous HCT. Fluorescent in-situ hybridization and IgVH mutation status data were available in 33 (56%) and 31 (53%) patients, respectively, being unfavorable (17p- or 11q-) in 22 (67%) and unmutated in 24 (77%) of them. All but 1 patient engrafted, and the median interval to neutrophil recovery (> 0.5 × 109/l) was 14 (range, 10–36) days. Twenty patients (34%), mostly from Cohort 1, received escalated donor lymphocyte infusions due to mixed chimerism or disease relapse. The overall complete response rate among 53 patients with measurable disease at the time of transplantation was 70%, whereas 21% had stable disease. Grade II-IV acute GVHD was observed in 14 (37%) and 12 (57%) patients from Cohorts 1 and 2, respectively (P = 0.17). Extensive chronic GVHD was observed in 3 (8%) and 10 (48%) patients from Cohorts 1 and 2, respectively (P < 0.01). The incidence of cytomegalovirus reactivation was not significantly different between cohorts (67% vs 47%, P = 0.23). With a median follow-up of 36 (range, 3–99) months for survivors, 18 (30%) patients have died, 3 of progressive disease and 15 of transplant-related complications. The 3-year overall survival (OS), progression-free survival (PFS) and non-relapse mortality were 66% (95% CI 48–84%), 38% (20–56%) and 21% (8–34%), respectively, for Cohort 1 and 65% (44–86%), 54% (32–76%) and 29% (10–48%) for Cohort 2 (P = 0.66; P = 0.33; and P = 0.53). Despite low patient numbers, alemtuzumab seemed particularly effective for unrelated donor recipients, with a 3-year OS and PFS of 54% and 40% for Cohort 1; and 33% and 0% for Cohort 2 (P = 0.02 and P = 0.07). In conclusion, results with reduced-intensity allogeneic HCT are promising for these poor-prognosis patients. Furthermore, the alemtuzumab-based regimen was effective in reducing the chronic GVHD rate with no negative effect on NRM, PFS or OS.

scholarly journals Total Body Irradiation without Chemotherapy as Conditioning for an Allogeneic Hematopoietic Cell Transplantation for Adult Acute Myeloid Leukemia

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Sultan Altouri ◽  
Mitchell Sabloff ◽  
David Allan ◽  
Harry Atkins ◽  
Lothar Huebsch ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Relapsed Disease ◽  
Acute Myeloid

Current therapies for acute myeloid leukemia (AML), failing induction, are rarely effective. We report our experience in 4 patients with AML who received 16 Gy TBI prior to allogeneic hematopoietic cell transplantation (alloHCT), between June 2010 and May 2011. Patients were 20 to 55 years of age, 2 with relapsed disease and 2 with AML failing induction. An HLA-matched graft from related or unrelated donor was infused on day 0. All but one, who received a CD34+-selected graft, received methotrexate and tacrolimus +/− antithymocyte globulin, as GVHD prophylaxis. The other patient received tacrolimus alone. Neutrophil and platelet engraftment occurred at a median of 18 and 14 days, respectively. Patients were discharged at a median of 28 days. There were no unexpected toxicities in the first 30 days. One patient had cytomegalovirus (CMV) viremia and anorexia, at two months. One patient had grade 2 acute GVHD of the skin. One patient developed chronic GVHD of the eyes, mouth, skin, joints, and lung at 4 months. Two patients died from relapse of their leukemia at days 65 and 125. Two patients remain in remission beyond day 1500. 16 Gy TBI followed by an alloHCT for AML, failing induction, is feasible and tolerable.

A Retrospective Comparison of Tacrolimus Vs. Cyclosporine for Immunosuppression After Allogeneic Hematopoietic Cell Transplantation with G-CSF-Mobilized Blood Cells

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2319-2319
Author(s):  
Yoshihiro Inamoto ◽  
Mary E.D. Flowers ◽  
Frederick R. Appelbaum ◽  
Paul A. Carpenter ◽  
H. Joachim Deeg ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Blood Cells ◽  
Myeloid Leukemia ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donors ◽  
Total Body

Abstract Abstract 2319 Background: Graft-versus-host disease (GVHD) is a common immunologic complication after allogeneic hematopoietic cell transplantation (HCT). Cyclosporine or tacrolimus in combination with other agents represent widely accepted standards of care as immunosuppressive regimens after HCT. Results of open-label randomized prospective phase III studies have indicated that the risk of grades II-IV acute GVHD after bone marrow transplantation with related or unrelated donors is lower with the use of tacrolimus as compared to cyclosporine, in combination with methotrexate. The current study was carried out to compare results with tacrolimus versus cyclosporine after HCT with G-CSF-mobilized blood cells. Patients and methods: The study cohort included 510 consecutive patients who received a first G-CSF-mobilized blood cell graft from related or unrelated donors after high-intensity conditioning for treatment of hematological malignancies between 7/1/2003 and 2009 at our center. All patients received ursodeoxycholic acid from 2 weeks before conditioning until 90 days after HCT to prevent hepatic complications, and all patients received immunosuppression with either tacrolimus or cyclosporine in combination with methotrexate after HCT. Endpoints included grades II-IV acute GVHD, grades III-IV acute GVHD, chronic GVHD, end of treatment for chronic GVHD, overall survival, disease-free survival, recurrent malignancy and nonrelapse mortality. Multivariate Cox regression models were used to evaluate hazard ratios for these endpoints with tacrolimus as compared to cyclosporine. The models were adjusted for patient age, donor type, recipient and donor gender combination, disease type, disease risk category, use of total body irradiation in the conditioning regimen, and year of HCT. The analysis was carried out as of July, 2010. Results: The median age of patients was 47 (range, 1 to 66) years. Diagnosis at HCT was acute myeloid leukemia in 200 (39%) patients, acute lymphoblastic leukemia in 73 (14%), chronic myeloid leukemia in 49 (10%), myelodysplastic syndrome or myeloproliferative disorders in 160 (31%) and other lymphoid malignancies in 28 (5%). Total body irradiation was used for conditioning in 168 (33%) patients. Of the 510 patients, 277 (54%) had HLA-matched related donors, 203 (40%) had HLA-matched unrelated donors, and 30 (6%) had HLA-mismatched related or unrelated donors. Outcomes according to immunosuppression with tacrolimus or cyclosporine are shown in Table 1. Multivariate analysis showed no statistically significant differences between tacrolimus and cyclosporine for any of the endpoints tested (Table 2), although the results showed a trend suggesting that the risk of non-relapse mortality might be lower with tacrolimus as compared to cyclosporine. Conclusion: In this retrospective analysis, tacrolimus offered no statistically significant advantage over cyclosporine for preventing grades II-IV acute GVHD after HCT with G-CSF-mobilized blood cells, and results for other outcomes also showed no statistically significant differences. Although our data support the hypothesis that either regimen could be an acceptable standard of care for immunosuppression, the number of patients analyzed in this study is not sufficient to completely exclude clinically meaningful differences in outcomes with the two regimens. Disclosures: Off Label Use: Tacrolimus and cyclosporine for immunosuppression after allogeneic hematopoietic cell transplantation.

Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Relapsed, Refractory, and Transformed Indolent Non-Hodgkin's Lymphoma

2008 ◽  
Vol 26 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Andrew R. Rezvani ◽  
Barry Storer ◽  
Michael Maris ◽  
Mohamed L. Sorror ◽  
Edward Agura ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Non Hodgkin's Lymphoma ◽  
Indolent Disease

Purpose Few effective treatment options exist for chemotherapy-refractory indolent or transformed non-Hodgkin's lymphoma (NHL). We examined the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in this setting. Patients and Methods Sixty-two patients with indolent or transformed NHL were treated with allogeneic HCT from related (n = 34) or unrelated (n = 28) donors after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Nine unrelated donors were mismatched for ≥ one HLA antigen. Sixteen patients had histologic transformation before HCT. Twenty patients (32%) had progressive disease after previous high-dose therapy with autologous HCT. Median age was 54 years, and patients had received a median of six lines of treatment before HCT. Median follow-up time after HCT was 36.6 months. Results At 3 years, the estimated overall survival (OS) and progression-free survival (PFS) rates were 52% and 43%, respectively, for patients with indolent disease, and 18% and 21%, respectively, for patients with transformed disease. Patients with indolent disease and related donors (n = 26) had 3-year estimated OS and PFS rates of 67% and 54%, respectively. The incidences of grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 and 4 acute GVHD, and extensive chronic GVHD were 63%, 18%, and 47%, respectively. Among survivors, the median Karnofsky performance status at last follow-up was 85%. Conclusion Nonmyeloablative allogeneic HCT can produce durable disease-free survival in patients with relapsed or refractory indolent NHL, even in this relatively elderly and heavily pretreated cohort. Outcomes were particularly good in patients with untransformed disease and related donors, whereas patients with transformed disease did poorly. Long-term survivors reported good overall functional status.

Outcomes of Allogeneic Hematopoietic Cell Transplantation in Acute Myeloid Leukemia Patients with Monosomal Karyotypes

2014 ◽  
Vol 133 (4) ◽  
pp. 327-335 ◽  
Author(s):  
Joon Ho Moon ◽  
Yoo Jin Lee ◽  
Sang Kyung Seo ◽  
Seo Ae Han ◽  
Joon Seok Yoon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Significant Risk ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Active Disease ◽  
Acute Myeloid

This study investigated the outcomes of allogeneic hematopoietic cell transplantation (allo-HCT) in acute myeloid leukemia (AML) patients with monosomal karyotypes (MK). A total of 114 AML patients who received allo-HCT were retrospectively analyzed. At the time of diagnosis, 13 patients were categorized with a favorable cytogenetic risk, 78 with an intermediate risk, and 23 with an adverse risk. MK was found in 12 patients among 23 with adverse cytogenetic risk. Pretransplant disease status was active disease in 5 cases (45.5%) in the adverse-risk without MK group, and 8 cases (66.7%) in the corresponding group with MK, 15 (19.2%) in the intermediate group and 4 (30.8%) in the favorable group. In multivariate analysis, active disease before transplant (hazard ratio, HR 3.913, p < 0.001), acute graft-versus-host disease (GVHD) ≥grade 2 (HR 1.908, p = 0.048) and chronic GVHD (HR 0.364, p = 0.001) affected overall survival (OS). The initial cytogenetic risk groups were not a significant risk factor for OS in allogeneic settings. The 2-year OS rate was 44.0 ± 15.9% without MK and 20.7 ± 17.9% with MK (p = 0.246). However, the OS rate was better for patients with chronic GVHD (p = 0.025). In conclusion, a survival benefit was observed for MK-positive patients with chronic GVHD in an allogeneic setting. However, the prognosis still remained poor for patients with MK. © 2014 S. Karger AG, Basel

Haploidentical Transplantation As Salvage Therapy For Disease Relapse After Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2084-2084
Author(s):  
Christiane Dorn ◽  
Sebastian P. Haen ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Median Time ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
The Other ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct

Abstract Introduction Therapeutic options and outcome for patients with relapse after allogeneic hematopoietic cell transplantation (HCT) are poor. For individual patients, a second or even third allogeneic HCT can be considered with curative intention. However, treatment-related mortality (TRM) and the risk of relapse after secondary allogeneic HCT are high. Therefore, the use of a haploidentical graft allowing for profound NK- and T-cell-alloreactivity after a reduced-intensity conditioning regimen (RIC) may optimize disease control by enabling potent graft versus leukemia effects and reduction of TRM. Methods We here retrospectively evaluated 26 consecutive patients undergoing haploidentical HCT as second (n=24) or third (n=2) allogeneic HCT at our center between 2003-2012. Diagnoses comprised relapse of AML (n=17) or ALL (n=7), blast crisis of CML (n=1) and transplant failure (n=1). There were 16 male and 9 female patients with a median age of 36 years (range 18-59). Results For RIC, fludarabin, thiotepa and melphalan were used in 16 patients, clofarabin, thiotepa and melphalan in 6 patients and other regimens containing variable combinations of cyclophosphamide, busulfan, TBI and treosulfan in 4 patients. Grafts were manipulated by CD3/CD19 depletion (n=19), TCRαβ depletion (n=1) or CD34 selection (n=6) and consisted of a median of 7.71 x 106 CD34+cells/kg bodyweight. The median interval from first HCT to second HCT was 18 months (range 5-145), and 10 and 16 months from second HCT to third HCT in the two patients undergoing a third HCT. Only 35% (n=9) of the patients receiving a second HCT were in complete remission (CR), while 65% (n=16) were in partial remission (PR). Among the patients receiving a third HCT, one had active disease, while the other was in CR. All patients achieved engraftment of the neutrophils at a median time of 11 days (range 8-26) and platelet engraftment was reached at a median time of 15 days (range 9-35, except one patient at day 375). At present, 5 patients (19%) are alive and in CR with a median follow-up of 1870 days (range 281-3941), while 35% (n=9) died from relapse; non-relapse-mortality was 46% (n=12). Kaplan-Meier estimated overall survival for all patients at 1 year was 33% (52% for patients in CR versus 18% in PR) and at 3 years 17% (26% for patients in CR versus 12% in PR). Causes of death in patients with second HCT included severe infections (n=8), organ failure (n=1), haemorrhage (n=1) and progressive multifocal leukoencephalopathy (n=2). Of the patients with third HCT, one died from respiratory insufficiency due to pulmonary haemorrhage, the other is still alive and in CR. Acute graft versus host disease (GVHD) occurred in 11 patients with predominantly mild presentation (grade 1: n=9, grade 2: n=2), limited chronic GVHD was apparent in 5 patients with no case of extensive GVHD. Conclusion Haploidentical HCT is a feasible salvage concept for patients with relapse after HCT with promising results even in patients not in CR. Disclosures: No relevant conflicts of interest to declare.

Prognostic implication of monosomal karyotype in patients with acute myeloid leukemia who received allogeneic hematopoietic cell transplantation.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6564-6564
Author(s):  
Yunsuk Choi ◽  
Sung-Doo Kim ◽  
Young-Hun Park ◽  
Jae Seok Lee ◽  
Dae-Young Kim ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Prognostic Impact ◽  
Free Survival ◽  
Monosomal Karyotype ◽  
Acute Myeloid

6564 Background: Monosomal karyotype (MK), defined as at least two autosomal monosomies or one single autosomal monosomy with one or more structural cytogenetic abnormalities, has been associated with worse outcomes in acute myeloid leukemia (AML). We evaluated the prognostic impact of MK on outcomes after allogeneic hematopoietic cell transplantation (allo-HCT) in AML. Methods: We retrospectively analyzed 169 adult patients with AML, who received allo-HCT in the first complete remission (CR) between 2000 and 2009. All patients had cytogenetic results at the diagnosis of AML. Patients were classified as having good, intermediate, or poor risk cytogenetics according to the NCCN guideline, and MK status was also determined. Results: MK was observed in 12 patients (7.1%); of whom, 11 patients also had complex karyotype (CK). Compared to patients without MK, those with MK had significantly lower overall survival (OS) (62.2% vs. 0%) and event free survival (EFS) (58.9% vs. 0%), and higher relapse probability (RP) (22.9% vs. 66.7%) at 5 years (all, p<0.001). 22 patients with CK also showed inferior outcomes, but CK with MK was associated with more inferior outcomes than CK without MK. Multivariate analysis showed that MK had a significantly adverse impact on OS (hazard ratio [HR], 5.192; p<0.001), EFS (HR, 4.531; p<0.001), and RP (HR, 6.558; p<0.001) after allo-HCT (Table). Conclusions: MK is a major prognostic factor predicting extremely worse outcomes in AML patients who underwent allo-HCT in the first CR. [Table: see text]

Ablative Allogeneic Hematopoietic Cell Transplantation in Adults 60 Years of Age and Older

2005 ◽  
Vol 23 (15) ◽  
pp. 3439-3446 ◽  
Author(s):  
Herschel Wallen ◽  
Theodore A. Gooley ◽  
H. Joachim Deeg ◽  
John M. Pagel ◽  
Oliver W. Press ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Blast Crisis ◽  
Progression Free Survival ◽  
Hematologic Malignancies ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct ◽  
Total Body

Purpose To evaluate outcomes of ablative allogeneic hematopoietic cell transplantation (HCT) in older patients with hematologic malignancies. Patients and Methods We treated 52 patients from 1979 to 2002 with a median age of 62.8 years (range, 60.1 to 67.8 years) using ablative preparative regimens followed by allogeneic HCT from sibling donors. Diagnoses included myelodysplastic syndrome (MDS; n = 35), chronic myeloid leukemia (CML; n = 8), acute myeloid leukemia (AML; n = 6), and other (n = 3). Conditioning regimens included cyclophosphamide (CY) and busulfan (BU) (67%), total-body irradiation and CY (21%), BU-fludarabine (10%), and CY (2%). Results Eighteen (35%) of 52 patients are alive at a median of 4.6 years (range, 0.8 to 9.1 years) after transplantation. Median overall survival (OS) and progression-free survival were 300 and 218 days, respectively. Three-year OS and relapse rates are estimated to be 34% and 24%, respectively. Nonrelapse mortality (NRM) rates at 100 days and 3 years are estimated to be 27% and 43%, respectively. Grade 3 to 4 acute graft-versus-host disease (GVHD) occurred in 20% of patients, and chronic extensive GVHD was described in 53% of patients. Fourteen (40%) of 35 patients with MDS are alive at a median of 2.8 years (range, 0.8 to 8.2 years). Four of six patients with CML in chronic or accelerated phase are alive at a median of 6.9 years (range, 4.1 to 9.1 years) after transplantation. None of the patients with AML, CML in blast crisis, or other diagnoses have survived. Patients who underwent transplantation after 1993 had improved survival. Conclusion These data suggest that allogeneic HCT is feasible in selected patients ≥ 60 years of age, although novel methods to reduce NRM while maintaining efficacy are needed.

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