Successful Rescue of Childhood Acute Leukemia In Non-Remission by Non-T-Cell Depleted HLA-Haploidentical Hematopoietic Cell Transplantation.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4582-4582
Author(s):  
Shogo Kobayashi ◽  
Atsushi Kikuta ◽  
Masaki Ito ◽  
Hideki Sano ◽  
Kazuhiro Mochizuki ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Complete Remission ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Myelogenous Leukemia ◽  
Haploidentical Hematopoietic Cell Transplantation

Abstract Abstract 4582 Refractory acute leukemia who do not achieve second or subsequent complete remission (CR) have an extremely poor prognosis. Non-T-cell depleted (TCD) HLA-haploidentical hematopoietic cell transplantation (haplo-HCT) is a form of adoptive cellular therapy that has a high degree of efficacy in hematologic malignancies. The major problems of non-TCD haplo-HCT are severe graft-versus-host disease (GVHD), graft failure (GF) and high-risk of early death. We conducted non-TCD haplo-HCT for children with acute leukemia in non-remission as a novel therapeutic strategy. Five consecutive children under 15 (0-13) years old with hematological malignancies underwent non-TCD haplo-HCT from family donors between November 2002 and July 2010 at Fukushima Medical University Hospital. All patients were in non-remission at transplantation. One donor was mother and the other 4 donors were fathers of the patients. One patient was in 3 loci, and 4 patients were mismatched 4 loci of the allele level for HLA-A, -B, -C and -DRB1. The blast count in the marrow before transplantation was 80%, 75%, 34%, 10% and 96%, respectively. There were two acute myelogenous leukemia and three acute lymphoblastic leukemia. There were two refractory diseases to chemotherapy and three relapses after HSCT. All of them received myeloablative conditioning (2 Busulfan based, 3 TBI based). Type of graft were bone marrow in one and peripheral blood stem cell in 4. Total of 9.9 ×108/kg of nucleated bone marrow cells were infused in the patient received BMT. The median number of TNC and CD34+ cell doses were 11 (8-21.4)×108/kg and 7.9 (6.5-8.8)×106/kg in PBSCT, respectively. GVHD prophylaxis were combination of tacrolimus, methotrexate was given in one patient, combination of tacrolimus, methotrexate and prednisolone in one, combination of tacrolimus, methotrexate, prednisolone, and antihuman thymocyte immunoglobulin (ATG) in 3. All patients achieved primary engraftment at median of 13 days (11 -15) and achieved complete remission. Five patients developed acute GVHD, with grade 1 in two patients, grade 2 in two patients, grade 3 in one patient. Chronic GVHD occurred in 2 of 4 evaluable patients. Infectious complications including 2 CMV reactivation, 1 CMV-IP, 1 invasive aspergillosis, 1 candida sepsis were observed. One patient died from CMV-IP in remission, remaining 4 patients survived disease-free + 4, + 9, + 10 and + 94 months after non-TCD haplo-HCT, respectively. These preliminary results suggested that non-TCD haplo-HCT is effective strategy in children with refractory leukemia. Disclosures: No relevant conflicts of interest to declare.

Successful Rescue of Refractory/Recurrent Myelogenous Leukemia by Allogeneic Hematopoietic Cell Transplantation and Prophylactic Immunotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4095-4095 ◽  
Author(s):  
Jing-Bo Wang ◽  
Tong Wu ◽  
Wan-Ming Da ◽  
Chun-Rong Tong ◽  
Xing-Yu Cao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Complete Remission ◽  
Nk Cells ◽  
Organ Failure ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Myelogenous Leukemia ◽  
Allogeneic Hct

Abstract Abstract 4095 Poster Board III-1030 The clinical outcomes of refractory/recurrent leukemia that salvaged by allogeneic hematopoietic cell transplantation (HCT) is usually poor. It is crucial for the management of those high-risk patients with appropriate conditioning regimens that balance the efficacy and safety well and with enhanced anti-leukemia effect post-HCT. Our previous study has shown that donor's dendritic cell-primed cytokine-induced killer cells (DC-CIK) is a safe and effective therapy in the management of early leukemia recurrence after allogeneic HCT, which fail to or ineligible for current standard treatment. Objective In present clinical study, we examine the efficacy of refractory/recurrent myelogenous leukemia salvaged by allogeneic HCT and prophylactic immunotherapy. Methods From September 2006 to May 2008, 30 patients with refractory/recurrent myelogenous leukemia (AML 29, CML-BC 1) were enrolled. The median age was 32 (12 to 55) years old. The median blasts in bone marrow were 36% (20% to 87%) prior to conditioning. The grafts were from HLA identical siblings (5), unrelated donors (7), and haploidentical family members (18). Conditioning regiments were individualized according to patients' status as following. Generally, the regimen with high-dose cytarabine plus BUCY2 was used (13 cases). The patients with impaired organ function received above regimen except with fludarabine instead of cyclophosphamide (11 cases). For the recipients with > 40% blasts in bone marrow, melphalan (2 cases) or aclarubicin (1 case) was added into the regimen or FLAG followed by reduced-intensified BUCY2 (3 cases) was employed in order to reduce leukemia burden. Cyclosporine A, methotrexate and mycophenolate mofetil were administrated for GVHD prophylaxis. To prevent leukemia relapse, immunosuppressants were tapered off early post-HCT. Prophylactic immunotherapy including cellular (DLI, DC-CIK, NK cells), and humoral (IL-2, IFN-a, thymosin) was used selectively in the patients who had no GVHD 120 days after HCT. Results The median mononuclear cells in the graft were 7.36 (3.49 to 11.5) ×108/kg. The median CD34+ cells were 4.06 (1.57 to 11.4) ×106/kg. The median CD3+ cells were 1.42 (0.75 to 3.61) ×108/kg. Twenty-nine patients attained sustained engraftment. One died of multi-organ failure before hematopoietic reconstitution. The median time for white blood cells > 1.0 × 109/L, and platelets > 20 × 109/L was 14 (10 to 21) days, 15 (12 to 26) days, respectively. Thirteen patients developed acute GVHD (grade I in 5, grade II in 7, and grade III in 1). Thirteen patients developed chronic GVHD after immunosuppressants' reduction or withdrawal. In addition, 13 patients received prophylactic immunotherapy due to lack of chronic GVHD 120 days post-HCT, then 7 of 13 developed chronic GVHD. With the median follow-up of 15 (3 to 35) months, two (6.7%) patients with AML had hematological recurrence. One patient attained durable complete remission again after treatment with chemotherapy followed by immunotherapy with DLI, DC-CIK, and NK cells. Five (16.7%) patients died (infections in 2, hematological relapse in 1, chronic GVHD in 1, and multi-organ failure in 1). 25 of 30 (83.3%) patients have been in continuous complete remission since salvaged HCT. Conclusion Our preliminary clinical results have shown that the combination of salvaged allogeneic HCT and prophylactic immunotherapy is a promising modality for the treatment of myelogenous leukemia in refractory/recurrent status, even with high leukemia burden. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Hematopoietic Cell Transplantation Can Cure Some Patients with Acute Leukemia in Relapse or Primary Induction Failure: A CIBMTR Study.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 528-528
Author(s):  
Michel Duval ◽  
Wensheng He ◽  
John P. Klein ◽  
Martin S. Tallman ◽  
John F. DiPersio ◽  
...  
Keyword(s):  
High Risk ◽  
Acute Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Karnofsky Score ◽  
Risk Criteria ◽  
Primary Induction ◽  
Induction Failure

Abstract Abstract 528 Acute leukemia refractory to chemotherapy is uniformly fatal without hematopoietic cell transplantation (HCT). However, the benefit of transplantation for patients not in complete remission (CR) is controversial. PATIENTS AND METHODS: 2,255 patients transplanted (at 252 centers in 38 countries) with an allogeneic donor after myeloablative conditioning regimen between 1995 and 2004 for acute leukemia in relapse or with primary induction failure were reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). 1,673 had acute myeloid leukemia (AML) and 582 acute lymphoblastic leukemia (ALL). Median age was 38 and 29 years for AML and ALL patients, respectively. Presence of circulating blasts, >25% marrow blasts, Karnofsky score < 90 %, or transplant in first relapse was observed in nearly half of the patients (see Table). RESULTS: 100 day mortality was 39% in AML and 41% in ALL. The median follow-up of survivors was 5 years. Overall survival (OS) was 19% (95% confidence interval (CI) 17-21) for AML and 16% (13-20) for ALL patients. For AML patients, five adverse pre-transplant variables significantly impacted OS : first CR duration < 6 months, blasts in the blood, donor other than HLA-identical sibling or partially matched unrelated, Karnofsky score < 90%, poor-risk cytogenetics. 106 AML patients had none of these high risk criteria, with a 3 years OS of 44% (35-54). For ALL patients, survival was worse with either: 1st refractory or ' 2nd relapse, ≥ 25% marrow blasts, CMV seropositive recipient, age ≥10 years. 8 ALL patients had no high risk criteria, with a 3 years OS of 85% (53-100). Grade 3-4 acute graft-vs-host disease (GVHD) occurred in 23% of AML and 27% of ALL patients. Chronic GVHD developed in 27%. Leukemia was the cause in 42 % of AML and 37% of ALL patients' deaths. CONCLUSIONS: 1. HCT can cure some patients with acute leukemia in relapse or with PIF, particularly those lacking defined high risk features. 2. These pre-transplant variables should be considered when deciding whether or not to offer HCT to such patients. Disclosures: No relevant conflicts of interest to declare.

Results of Allogeneic Hematopoietic Cell Transplantation in Persons with Fanconi Anemia and Pretransplant Cytogenetic Abnormalities, Myelodysplastic Syndrome, or Acute Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 838-838
Author(s):  
Mouhab Ayas ◽  
Jennifer Le-Rademacher ◽  
H. Joachim Deeg ◽  
Robert Peter Gale ◽  
Stella M. Davies ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Acute Leukemia ◽  
Myelodysplastic Syndrome ◽  
Cell Transplantation ◽  
Fanconi Anemia ◽  
Cumulative Incidence ◽  
Graft Failure ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Conditioning Regimens

Abstract Abstract 838 Background: Allogeneic hematopoietic cell transplantation (HCT) can cure bone marrow failure in persons with Fanconi anemia (FA). However, results in those with pretransplant cytogenetic abnormalities (CA), myelodysplastic syndrome (MDS) or acute leukemia (AL) are less favorable, although only limited data are available. Thus, the current study was designed to use data from the Center for International Blood and Marrow Transplant Research (CIBMTR) to evaluate the outcomes of these patients after HCT. Patients and Methods: This is a retrospective analysis of 113 FA patients with CA (n=54), MDS (n=45), or AL (n=14) before allogeneic HCT, and who were reported to CIBMTR from 1985 to 2007 by 46 centers worldwide. Overall survival (OS) probability was estimated using the Kaplan-Meier method. Engraftment and acute and chronic graft-vs-host-disease (GvHD) were determined using cumulative incidence estimates to accommodate competing risks. Univariate analyses were conducted to evaluate the prognostic impact of key variables. The small sample size precluded multivariate analysis. Fifty four patients had CA including complex abnormalities (n=18), chromosome (Chr) 1 abnormalities (n=8), chr 3 abnormalities (n=1), chr 5 abnormalities (n=3), chr 7 abnormalities (n=4) and other non-complex abnormalities (n=20). Pretransplant conditioning regimens were radiation-based in 67 patients and chemotherapy-based in 46 patients. The donor source was bone marrow/peripheral blood (matched related, n=82; unrelated, n=16), or cord blood (related, n=2; unrelated, n=13). Results: Absolute neutrophil count (ANC) recovery occurred in 78% and 85% of patients, at day 28 and day 100, respectively. At day 100, the cumulative incidences of acute GvHD grade II–IV and III–IV were 26% (95% confidence intervals [CI] 19–35), and 12% (95% CI 7–19), respectively. Chronic GvHD cumulative incidences were 20%, 23%, and 23% at 1, 3, and 5 years, respectively. Primary graft-failure occurred in 18 patients. Cumulative incidence of secondary graft-failure at 2 years was 9% (95% CI 4–15). Survival probabilities were 64%, 58%, and 55% at 1, 3, and 5 years, respectively. Exclusion of subjects with chr 1 abnormalities did not alter the results (log-rank P value=.81). In univariate analysis, among the entire cohort, none of the following variables affected survival: use of fludarabine or radiation in the conditioning regimen, the presence of AL/MDS as compared to only CA, or year of transplant. Age at transplant was the only variable significantly correlated with 5-year OS (≤ 14 years vs. > 14 years, 69% vs. 39%, respectively; P =0.001). When analysis was restricted to recipients of related donor HCT (n=82), age again correlated with 5-year survival (≤ 14 years vs. > 14 years, 78% vs. 34%, respectively; P <.001); additionally, patients with CA pretransplant had better survival than those with MDS or AL (5-year OS: 67% vs. 43%, P =0.03). Conclusion: Our analysis indicates that persons with FA and pretransplant CA, MDS, or AL have a reasonable survival with HCT. The analysis also suggests that survival may be better in younger persons and in those with only CA pretransplant. No firm conclusions can be drawn from this study regarding the impact of the conditioning regimens; the current data, however, suggest that radiation-based conditioning regimens are not associated with a survival advantage as has been suggested by previously published data. Disclosures: No relevant conflicts of interest to declare.

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