Risk Factors of Outcomes after Haploidentical Hematopoietic Stem Cell Transplants for Children with High Risk Acute Leukaemia. A Survey on Behalf of the EBMT.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 440-440
Author(s):  
Jaqueline Cornish ◽  
Thomas Klingebiel ◽  
Myriam Labopin ◽  
Phillip J. Darbyshire ◽  
Rachel Hough ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Acute Leukaemia ◽  
Disease Status ◽  
Hematopoietic Stem ◽  
Alternative Option ◽  
Advanced Phase

Abstract In the absence of an HLA identical donor, T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT) is an alternative option to treat children with high risk or relapsed acute leukaemia. However very few data is available in a large series of children. With the aim to study risk factors of outcomes we have analyzed 196 children (<16 years old) with ALL (n=131) or AML (n=65) transplanted with a T-cell depleted bone marrow (n=18) or peripheral blood related haploidentical HSCT from 1995 to 2004 in Europe. The median age was 8 years and median follow-up 22 months. In the AML group, 13 (20%) children were transplanted in CR1, 22 (34%) in CR2 and 30 (46%) in advanced phase and in ALL group, 28 (21%) in CR1, 74 (56%) in CR2 and 81 (62%) in more advanced phase. The majority of the patients did not receive drugs for GVHD prophylaxis and all received myeloablative conditioning (61% of TBI). Cumulative incidence with competing risk and KM estimates were used to calculate outcomes probabilities. The median days of neutrophil recovery was 14 days (4–72) and 85% of patients had signs of engraftment. Acute GVHD II–IV was observed in 17% of the patients (8% had grade III–IV). Two-years overall LFS, relapse incidence and TRM were 27±4%, 43±3%, 30±3%, respectively. Patients transplanted with AML or ALL had similar outcomes. LFS was 28±6%for AML and 27±4% for ALL. Among the risk factors analysed only the disease status at transplantation was associated with LFS and relapse incidence. Outcomes are listed below according to disease status at transplant. Outcomes at two years CR1 (n=41) CR2 (n=74) Advanced (n=81) p value Transplant related mortality 32+/−8% 26+/−5% 33+/−5% 0.44 Relapse 32+/−8% 40+/−6% 51+/−6% 0.03 Leukaemia free survival 36+/−8% 34+/−6% 16+/−4% <0.0001 In fact, in a multivariate analysis for LFS and relapse only patients transplanted in remission had better LFS and decreased relapse incidence compared with non remission patients (p<0.001 and p=0.006, respectively). No risk factor was found to be associated with TRM. Most frequently, causes of death were relapse (60%) or infections (22%). In conclusion, haploidentical HSCT is an alternative option to treat children with high risk acute leukaemia in the absence of HLA identical donor.

scholarly journals Tandem autologous hematopoietic stem cell transplantation for treatment of adult T-cell lymphoblastic lymphoma: a multiple center prospective study in China

Haematologica ◽  
2019 ◽  
Vol 106 (1) ◽  
pp. 163-172 ◽  
Author(s):  
Yao Liu ◽  
Jun Rao ◽  
Jiali Li ◽  
Qin Wen ◽  
Sanbin Wang ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Status ◽  
Lymphoblastic Lymphoma ◽  
Hematopoietic Stem ◽  
Chemotherapy Group

T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive form of lymphoma with poor clinical outcomes and lacks of a standard treatment regimen. In this study, we assessed the safety and efficacy of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) strategy for adult T-LBL and evaluated prognostic factors affecting survival. 181 Newly-diagnosed adult T-LBL patients were enrolled, 89 patients were treated with chemotherapy alone, 46 patients were allocated to single auto-HSCT group, 46 patients were treated with tandem auto-HSCT. The median follow-up time was 37 months, the 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (26.5% vs 53.1% and 54.8%). The 3-year PFS and OS rate of the tandem auto-HSCT group (73.5% and 76.3%) were significantly higher than those of the single auto-HSCT group (46.9% and 58.3%) and the chemotherapy group (45.1% and 57.1%). In the tandem auto-HSCT group, age and disease status after the first transplantation impacted the OS and PFS. Multivariate analysis identified that disease status after the first transplantation was the only independent prognostic factor for patients treated with tandem-HSCT. In addition, diagnostic models of the initial CD8+CD28+/CD8+CD28- T cell ratio in predicting the disease status were found to be significant. Taken together, tandem auto-HSCT can be considered an optimal strategy for adult T-LBL patients (ChiCTR-ONN-16008480).

Results of T Cell Depleted (TCD) Myeloablative Hematopoietic Stem Cell Transplants (HSCT) in Patients with Hematologic Malignancies ≥ 55 yrs of Age.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3660-3660
Author(s):  
Ann A. Jakubowski ◽  
Esperanza B. Papadopoulos ◽  
Hugo R. Castro-Malaspina ◽  
Katharine Hsu ◽  
Miguel-Angel Perales ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
High Risk Patient ◽  
Disease Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Conditioning Regimens ◽  
Good Risk

Abstract Allogeneic HSCT remains the only curative therapy for many patients(pts) with hematologic diseases. Studies have suggested that older pts experience greater toxicity from the intensive chemo-radiotherapy used in myeloablative conditioning regimens. As a consequence, many older pts are now offered non-myeloablative transplants (NMAT) for malignant conditions where a graft vs. tumor effect (GvT) is expected to provide the antitumor effect in place of the chemo-radiotherapy. Unfortunately, graft vs. host disease (GvHD) remains a common occurrence after conventional transplants, occurring more frequently in older pts and unrelated donor transplant recipients, resulting in significant morbidity and mortality. Furthermore, the efficacy of NMAT is limited by the disease status at time of transplant and by the susceptibility of the hematologic disease to a GvT effect. TCD of hematopoietic stem cell grafts offers an alternative to older pts, in particular those requiring unrelated donor transplants (URD), with the advantage of a reduced incidence of GvHD. From 1995–2005, 57 patients ≥55 yrs received myeloablative TCD transplants at our institution. The median age was 58.2 (range 55–69.2) yrs. Stem cell sources were TCD bone marrow, PBSC or both. Thirty-seven received transplants from related donors (RD), including two mismatched, and 20 received transplants from unrelated donors (URD), 9 of whom were mismatched. In addition to their advanced age, many of these pts were considered high risk based on the status of disease, HLA mismatch, and history of previous therapy. Twenty-three pts were considered “good risk” by disease status (CML-CP1, AML-CR1, CR2) and 34 pts were considered poor risk (&gt;CML-CP1, &gt;AML CR2, MDS, NHL, &gt;ALL CR1, ABL.) BM was TCD by soybean agglutination followed by sheep red blood cell rosetting (E), and PBSCs by CD34+ selection and E-rosetting. Conditioning regimens included total body irradiation (TBI) in addition to thiotepa and cyclophosphamide, or thiotepa and fludarabine. The non-TBI preparative regimen consisted of busulphan, melphalan and fludarabine. Anti-thymocyte globulin was used as rejection prophylaxis for all TCD transplants until 2001 when it was eliminated from the TBI containing regimen for matched RD transplants. A total of 25 pts (15 matched RD and 10 URD, 6 of whom were mismatched) are alive following TCD transplants with a median follow up of 24 mos. for RDs and 12 for URDs. Of the survivors, 2/10 URD and 14/15 RD recipients received TBI containing regimens based on the triage system at our center. Three pts with CML-CP1, one with CML-acc and one with AML-CR1 showed evidence of minimal residual disease, received donor leukocyte infusions and subsequently achieved longterm continued CR. The incidence of post-transplant GvHD was low despite the high number of mismatched URD transplants - 1 Grade IV (RD), 2 Grade 3 and 1 Grade 1 (URD). The 100 day mortality was 15%. Overall and current disease free survival for ‘good risk’ patients based on disease status is 58% for RD and 60% for URD. Although longer follow up is necessary to confirm these results, the promising DFS rates in association with a low incidence of GvHD in this older and relatively high risk patient population support further investigation of myeloablative TCD HSCT in these patients.

Incidence, Risk Factors and Clinical Outcome Of Leukemia Relapses Due To Loss Of The Mismatched HLA Haplotype After Partially-Incompatible Hematopoietic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 918-918
Author(s):  
Lara Crucitti ◽  
Roberto Crocchiolo ◽  
Cristina Toffalori ◽  
Maria Teresa Lupo Stanghellini ◽  
Andrea Assanelli ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cells ◽  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Leukemic Cells ◽  
Hematopoietic Stem ◽  
Immune Pressure ◽  
Hla Loss

Abstract Introduction Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) represents the best curative option for many patients with high-risk myeloid malignancies, mainly due to its potent immuno-mediated antileukemic effect. Still, post-transplantation relapse remains an unsolved issue. We and others described genomic loss of the mismatched HLA haplotype as a mechanism by which leukemic cells evade donor T cell-mediated immune pressure and cause clinical relapse after partially HLA-incompatible HSCT (Vago et al, N Engl JMed, 2009), but the actual incidence and risk factors of this phenomenon are to date largely unknown. Methods We analyzed retrospectively 224 consecutive partially HLA-mismatched HSCTs performed in our Institute in the last ten years (Unrelated Donor, UD: 60; Mismatched Related Donor, MMRD: 164) in patients affected by myeloid malignancies (Acute Myeloid Leukemia, AML: 173; Myelodisplastic Syndrome, MDS: 27, Myeloproliferative Neoplasms: 17; others: 7). All patients received myeloablative conditioning and infusion of donor T cells, either as part of the graft or as an add-back. Patients’ follow-up included bone marrow genomic HLA typing to identify HLA loss relapses. In selected cases of HLA loss relapse cryopreserved serial serum samples harvested after HSCT were analyzed for the eventual presence of anti HLA Class I or Class II antibodies. Results We documented 77 cases of relapse: 66 after MMRD and 11 after UD HSCT. Out of 77 relapses 21 (27%) were due to genomic loss of the mismatched HLA in leukemic cells. HLA loss occurred in 19 patients with AML, one with MDS and one with myelofibrosis. All the 21 cases of HLA loss occurred after MMRD HSCT (32%), so the analysis for putative risk factors were limited to this subgroup of transplants (n=164), comparing the frequencies of putative risk factors between patients with HLA loss and “classical” relapses (n=21 and 45, respectively). HLA loss relapses occurred significantly later than their classical counterparts (median time to relapse 307 vs 86 days, p<0.0001) in this very high-risk population, suggesting that outgrowth of the mutant variants require a considerable lapse of time. None of the disease-related factors we addressed (amongst which disease subtype, cytogenetics, molecular profile and disease status at HSCT) correlated significantly with eventual HLA loss. Use of an unmanipulated T cell-repleted graft resulted to be a risk factor for HLA loss relapses (Chi2=6.36; p=0.01). Both acute (HR:4.67, CI 95%: 1.53-14.22; p=0.007) and chronic (HR: 1.71; CI 95%: 0.68-4.28; p=0.01) Graft-versus-Host Disease (GvHD) occurred more frequently in patients with HLA loss relapses. Intriguingly, HLA-C*04 was more frequent in the mismatched haplotype of patients with HLA loss as compared to those with classical relapse (Chi2= 8.07; p=0.04), possibly suggesting an higher immunogenicity of the allele, hinted also by a similarly higher frequency in patients who did not relapse (Chi2=2.77; p=0.096). In our series, predicted NK alloreactivity had no apparent impact on eventual HLA loss. In none of the five patients studied to date we could evidence circulating anti-HLA antibodies, suggesting that humoral immunity does not play a major role in this phenomenon. Since lymphocyte infusions from the original donor are expected to be inefficacious to treat HLA loss relapses, whenever fit these patients were candidate to re-transplantation from alternative donors, HLA-mismatched and putatively alloreactive against the relapsed leukemia. Still, outcome was poor, with 5 of 8 re-transplanted patients dying of transplant-related mortality and only one alive in complete remission at a follow-up of 18 months. Conclusions Genomic loss of the mismatched HLA haplotype is an extremely frequent mechanism of leukemia immune evasion and relapse after MMRD HSCT. It appears to be prompted by selective immune pressure mediated by donor-derived T cells, and accordingly occurs more frequently upon T cell-repleted transplants and in the presence of acute and chronic GvHD, clinical hallmarks of T cell alloreactivity. Conversely the role of NK and B cells in HLA loss needs further investigation, but appears to date less pronounced. Given the poor outcome of re-transplantation, mainly due to toxicity, novel diagnostic and therapeutic approaches are needed to anticipate the detection and improve the treatment of these frequent variants of leukemia relapse. Disclosures: Bordignon: MolMed SpA: Employment. Bonini:MolMed SpA: Consultancy.

scholarly journals Tandem Autologous Hematopoietic Stem Cell Transplantation Treatment for Adult T-Cell Lymphoblastic Lymphoma: A Multiple Center Prospective Study in Southwestern China

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5747-5747
Author(s):  
Yao Liu ◽  
Jun Rao ◽  
Jiali Li ◽  
Qin Wen ◽  
Shifeng Lou ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Disease Status ◽  
Lymphoblastic Lymphoma ◽  
Hematopoietic Stem ◽  
Chemotherapy Group

Abstract Backgroud T-cell lymphoblastic lymphoma (T-LBL) is a highly aggressive lymphoma with very poor clinical outcomes which has not standard treatment. This study evaluated the efficacy and safety of tandem autologous hematopoietic stem cell transplantation (auto-HSCT) treatment for adult T-LBL and assessed the factors that affect survival. Methods 160 newly diagnosed adult T-LBL patients were divided into three groups: chemotherapy group (68 patients), single auto-HSCT group (46 patients), and tandem auto-HSCT group (46 patients). The primary outcome measure was failure-free survival. The intermediate primary outcomes were progression/relapse rate and overall survival. Factors influencing toxicity related to tandem auto-HSCT treatment and prognosis for the patients were analyzed as well. Results The 3-year progression/relapse rate of the tandem auto-HSCT group was significantly lower than that of the single auto-HSCT group and chemotherapy group (19.6% vs 45.7% and 70.6%, p < 0.05). The 3-year PFS rate and OS rate of the tandem auto-HSCT group (68.3% and 72.5%, respectively) were significantly higher than those of the single auto-HSCT group (41.5% and 55.4%, respectively, p < 0.05) and the chemotherapy group (23.3% and 43.3%, respectively, p < 0.05). In the tandem auto-HSCT group, age and disease status after the first transplant had an influence on the OS and PFS. Multivariate analysis identified disease status after the first transplant as the only independent prognostic factor for outcome in T-LBL. Conclusions Tandem auto-HSCT improves long-term survival of adult T-LBL patients. Disease status after the first transplant was an independent prognostic indicator for those patients. Disclosures No relevant conflicts of interest to declare.

Risk Factors for Outcome after Haploidentical Hematopoietic Stem Cell Transplant in Children with Very High Risk Acute Lymphoblastic Leukemia: Impact of Centre Experience. A Survey on Behalf of the ALWP and PDWP of the EBMT.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 438-438 ◽  
Author(s):  
Thomas Klingebiel ◽  
Jacqueline Cornish ◽  
Myriam Labopin ◽  
Franco Locatelli ◽  
Adriana Balduzzi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
Lymphoblastic Leukemia ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Alternative Option ◽  
Significant Difference ◽  
Very High

Abstract In the absence of an HLA identical donor, T-cell depleted haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) is an alternative option to treat children with very high risk acute lymphoblastic leukemia (ALL). However, little data is available in children. We have analyzed 118 children (≤16 years old) with ALL transplanted with a myeloablative Haplo-HSCT from 1995 to 2004 in Europe. Only transplants with 2 or more HLA disparities out of 6 (A, B and DRB1) were included. The median age was 8.5 years and median follow-up 56 months (8–116). At transplant, 21 (18%) were in CR1, 72 (61%) in CR2 or CR3 and 25 (21%) in more advanced phase. The 3-year leukemia free survival was 32±10%, 28±5% and 0%, respectively. Therefore we restricted the analysis to patients in remission (n=93) transplanted in 30 EBMT centers. Thirty-four (37%) patients were treated in centres performing more than 10 Haplo-HSCT in the study period (3 centres). The median age of recipient and donor was 8.7 and 37 years, respectively. Fifty four (65%) received a full Haplo-HSCT and 95% of the donors were parental. Twenty seven (29%) had t(9;21) or t(4;11). The majority of patients did not receive drugs for GVHD prophylaxis, ATG/ALG was used in conditioning in 74%, and 73% received TBI. The Clinimacs® device was used in 74% of selections. The median number of CD34+ cells infused was 12.8 106/Kg. Cumulative incidence with competing risk and KM estimates were used to calculate outcome probabilities. The median days of neutrophil recovery was 15 days (8–55) and 90% of patients had signs of engraftment. Acute GVHD II–IV was observed in 24% of the patients. In univariate analysis for LFS there was a trend towards better results for patients receiving higher CD34 cell dose (p=0.08) and a significant difference for patients transplanted in centres performing more Haplo-HSCT (49% versus 17%, p=0.002). Relapse incidence (RI) and non relapse mortality NRM) tended to be different between the experienced and less experienced centres. In less experienced centres NRM was 41% vs 27% (p=0.13) and RI 41% vs. 24% (p=0.10). There were patient, donor and transplant related differences between less and more experienced centres, specifically related to donor sex, Philadelphia positivity, year of transplantation, use of TBI, ATG and DLI and previous autograft. In conclusion, Haplo-HSCT is an alternative option to treat children with very high risk ALL in the absence of HLA identical donor. Centres with more experience have better LFS.

T-Cell Depleted Allogeneic Hematopoietic Stem Cell Transplantation For Patients With Relapsed Multiple Myeloma and High-Risk Cytogenetics Permits Long-Lasting Remissions In The Absence Of Graft-Versus-Host Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2115-2115
Author(s):  
Guenther Koehne ◽  
Sean M. Devlin ◽  
Heather Landau ◽  
Hani Hassoun ◽  
Alex Lesokhin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
T Cell ◽  
High Risk ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Salvage Chemotherapy ◽  
Hematopoietic Stem ◽  
Graft Versus Host

Abstract Introduction Pts with high-risk cytogenetics and/or relapsed multiple myeloma (MM) post autologous transplant have a particularly limited prognosis. Conventional allogeneic hematopoietic stem cell transplantation (allo HSCT) has been associated with unacceptably high rates of mortality and non-myeloablative allo HSCT has resulted in high rates of acute and chronic graft-versus-host disease (GvHD) and progression. Methods We report results of a phase II clinical trial of 34 pts, using T-cell depleted allo HSCT (allo TCD HSCT) from HLA compatible (matched related = 12, matched unrelated = 13, and mismatched unrelated = 9) donors. All 34 pts had relapsed myeloma within 15 mos following auto HSCT, and 26/34 pts also had high-risk cytogenetics at diagnosis [t(4;14), t(14;16), del17p by FISH and/or del13q by karyotyping]. All pts had to achieve at least a partial response from preceding salvage chemotherapy (n=26) or second salvage auto HSCT (n =8). Pts underwent allo TCD HSCT with busulfan (0.8mg/kg x 10 doses), melphalan (70mg/m2 x 2 days), fludarabine (25mg/m2 x 5 days) and rabbit ATG (2.5mg/kg x 2 days). T-cell depletion was performed by positive CD34 selection (Isolex) followed by rosetting with sheep erythrocytes for the initial 13pts (2008-09) and by CD34+ enrichment by the Miltenyi Device in 21pts thereafter, achieving < 104CD3+/kg for all grafts. None of these pts received immuno suppressive therapy post TCD HSCT. Pts with 10/10 HLA matched donors were also eligible to receive low doses of donor lymphocyte infusions (DLI) (5x10e5 – 1x10e6 CD3+/kg) no earlier than 5mos post allo HSCT. Results 34 pts with a median follow up of 31.6mos (range: 7.6 – 65.1 mos) of survivors are reported, median age 56 years (range 32 – 69). All pts engrafted promptly (median d+10, range d+9 to +12).TRM and acute GvHD (grade II-IV) at 12mos is 9% (95% CI: 2% – 23%) and 6% (95% CI: 1% – 17%). Chronic GvHD was not observed in any pt. The overall survival (OS) and progression-free survival (PFS) with their 95% confidence intervals (CI) are shown in Table 1. Factors associated with worse outcome were disease status and number of previous treatments prior to TCD HSCT. (Table1; Figure 1) 15/34 pts are alive, 10/15 pts are in complete remission (CR), 4 pts are have been in continued CR for 44, 53, 62 and 65mos post allo TCD HSCT. 5/15 pts alive have progressed and 4/5 pts are currently responding to salvage chemotherapy and/or DLI. 14/19pts pts died of disease progression, 3/19 died of infectious complications and 2 pts died of complications associated with acute GvHD. Conclusion Long-lasting disease control can be achieved with TCD HSCT in pts with multiply relapsed MM including those with high-risk cytogenetics in the absence of chronic GvHD. TRM and acute GvHD are low in these heavily pretreated pts. Outcome of TCD HSCT is influenced by numbers of regimens administered and disease status prior to allo BMT. Pts who failed to respond to standard chemotherapeutics pretransplant responded to reuse of this therapy post TCD HSCT. Based on these results, we are aiming to perform TCD HSCT for pts with MM who have high-risk cytogenetics at an earlier time point before multiple relapses develop and to integrate post transplant immunotherapeutic or immunomodulatory strategies to further reduce risk of relapse in these high-risk pts. Disclosures: No relevant conflicts of interest to declare.

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