Intermediate Intensity Conditioning Followed by Allogeneic Peripheral Blood Stem Cell Transplantion for Treatment of High Risk Relapse of Aggressive Lymphoma. Interim Analysis of the DSHNHL R3 Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3043-3043
Author(s):  
Bertram Glass ◽  
Justin Hasenkamp ◽  
Peter Dreger ◽  
Martin Gramatzki ◽  
Joerg Schubert ◽  
...  
Keyword(s):  
Progressive Disease ◽  
Cell Lymphoma ◽  
Observation Time ◽  
High Dose ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors ◽  
To Receive ◽  
Relapse Rates

Abstract High dose therapy (HDT) followed by autologous stem cell support has poor outcome in patients with primary progressive lymphoma or relapse after primary HDT due to high relapse rates and failure free survival below 20%. Allogeneic SCT may help these patients by exerting an GVL effect. Its use however, is followed by high incidence of severe GVHD and treatment related mortality (TRM) in this population. The anti-CD20 monoclonal antibody rituximab has been claimed to solve this problem. We initiated a randomized phase II study using intermediate conditioning (Fludarabine 125 mg/m2, Busulfan 12 mg/kg and cyclophosphamide 120 mg/kg) followed by GVHD prophylaxis with short term mycophenolat mofetil plus tacrolimus. Patients were randomized to receive two times four doses of rituximab (375 mg/m2) post transplant starting day +28 and day +175 or no further GVHD prophylaxis. Here we report the results of a first interim analysis. From January 2005 to August 2007 sixty patients (pts) with aggressive NHL were enrolled. Thirty one pts had diffuse large B cell NHL, 9 patients follicular lymphoma grade 3, 8 pts blastic mantle cell lymphoma, one patient aggressive marginal zone lymphoma and 11 patients peripheral T cell lymphoma. The median number of prior treatment regimens was 3 (range 1 to 6). 43 (72%) pts received at least one cycle of high-dose therapy and autologous SCT prior to alloSCT; 79% had early relapse (< 12 months) or primary progressive disease, 58% chemo-refractory disease and 52% had progressive disease with high or high intermediate age adjusted IPI immediately prior to conditioning. Allo-PBPC were obtained from HLA-identical siblings in 16 pts, from fully matched unrelated donors in 32 pts and from 1 locus mismatched unrelated donors in 12 pts. Engraftment of leukocytes was rapid (median 10 days, range 8–27) and all patients achieved complete (> 95%) donor type chimerism after alloSCT. Median observation time is 8 months (range 1–35 months). 32 pts died, in 20 patients death was attributed to treatment related causes. After one year, estimated overall survival is 47%, failure free survival is 43%, TRM is 37%, relapse rate is 33% and incidence of GVHD > grade 1 is 57%. With an observation time precluding final analysis, there are no significant differences between patients randomized to receive rituximab post transplant and those who were not. There was a trend to lower relapse rates in patients with GVHD > grade 1 (25% vs 44%, p=0.14). Intermediate intensity conditioning followed by allogeneic SCT is a valuable treatment option in patients with high-risk relapse of aggressive NHL. The basic incidence of GVHD and TRM is high. Due to the short observation time, a definitive conclusion regarding the impact of post transplant Rituximab cannot be drawn. The study will be continued.

Rituximab for Graft-Versus-Host-Disease-Prophylaxis after Allogeneic Stem Cell Transplantation Given as Treatment of High Risk Relapse of Aggressive Lymphoma: Results of a Randomized Phase II Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1974-1974 ◽  
Author(s):  
Bertram Glass ◽  
Justin Hasenkamp ◽  
Anke Görlitz ◽  
Peter Dreger ◽  
Jörg Schubert ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
B Cell ◽  
Phase Ii ◽  
Progressive Disease ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Randomized Phase Ii ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors

Abstract Background: High dose therapy (HDT) followed by autologous stem cell support has poor outcome in patients with primary progressive lymphoma or relapse after primary HDT. Allogeneic SCT may help these patients by exerting an GVL effect. Its use however is hampered by high incidence of severe GVHD and non-relapse mortality in this population. Rituximab has been claimed to reduce the incidene of GVHD without negative impact on the relapse rate. Patients and Methods : We initiated a randomized phase II study using intermediate conditioning (Fludarabine 125 mg/m2, Busulfan 12 mg/kg and cyclophosphamide 120 mg/kg) followed by GVHD prophylaxis with short term mycophenolat mofetil plus tacrolimus. Anti-thymozyte globulin (ATG) was given due to center decision. Patients were randomized to receive two times four doses of rituximab (375 mg/m2) post transplant starting day +21 and day +175 or no additional GVHD prophylaxis. From June 2004 to July 2007 sixty five patients with aggressive NHL were enrolled and 59 were eligible for analysis. Thirty one pts had diffuse large B cell NHL, 3 patients follicular lymphoma grade 3, 7 pts blastic mantle cell lymphoma, 2 pts aggressive marginal zone lymphoma, 2 patients lymphoblastic B cell lymphoma, and 12 T cell lymphoma. 42 (71%) pts received at least one cycle of HDT and autologous SCT prior to alloSCT; 78% had early relapse ( &lt; 12 months) or primary progressive disease, 59% chemo-refractory disease and 48% had progressive disease with high or high intermediate age adjusted IPI immediately prior to conditioning. Results: Allo-PBPC were obtained from HLA-identical siblings in 17 pts, from matched unrelated donors in 32 pts and from one locus mismatched unrelated donors in 10 pts. 33 patients did receive ATG. Median observation time of surviving patients is 1,8 years. 30 pts died, in 19 patients death was attributed to treatment related causes. After one year, estimated overall survival is 49%, progression free survival is 39%, relapse rate is 28 % and incidence of GVHD &gt; grade 1 is 73%. The last documented lymphoma progress occurred at day 288 after alloSCT. There are no significant differences in OS, PFS and GvHD in relationship to the application of Rituximab. Conclusion: Intermediate intensity conditioning followed by allogeneic SCT is a valuable treatment option in patients with high-risk relapse of aggressive NHL. The incidence of GVHD and non-relapse mortality is high. On the background of this very high basic incidence of GVHD, we did not find a significant impact of post transplant rituximab on GVHD, relapse rates or survival, respectively. Therefore, ATG will be added as an obligatory part of the conditioning regimen in the next study phase in additional 30 patients

scholarly journals Improved GvHD-Free, Relapse-Free Survival (GRFS) with Post-Transplant Cyclophosphamide and Tacrolimus for GvHD Prevention in Older Adults Undergoing Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2760-2760
Author(s):  
Paola Andrea Charry ◽  
Maria Queralt Salas ◽  
Alexandra Pedraza ◽  
María Suárez-Lledó ◽  
Nuria Martínez-Cibrian ◽  
...  
Keyword(s):  
Older Adults ◽  
Cell Transplantation ◽  
Cumulative Incidence ◽  
Older Patients ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Relapse Rates

Abstract INTRODUCTION The continuous refinement of transplant techniques has lead to a reduction of transplant-related toxicity resulting on an increasing number of allogeneic hematopoietic cell transplantation (alloHCT) performed in older patients. Since 2014, post-transplant cyclophosphamide (PTCy) with tacrolimus (PTCy-TK), alone, has been progressively implemented at our Institution as GvHD prophylaxis for related, matched and mismatched unrelated donor transplantation (MRD, MUD, MMUD). The experience has proved that the use of this prophylaxis induces effective GvHD prevention without increased relapsed rates (Pedraza et al, 2021). Secondary to the encouraging results obtained from the use of PTCy-TK at our Institution, and considering that older patients with hematological disorders are a group of patients with higher risk to develop transplant-related toxicity, this study compares, as far as we know, the results provided by the use of PTCy-TK with conventional GVHD prophylaxis in a consecutive cohort of patients older than 50 years. METHODS Between January 2014 and June 2020, 147 adults with hematological malignancies and &gt; 50 years underwent alloHCT either from MRD or UD at our Institution. Seventy-two (48.9%) patients received PTCy 50 mg/kg/day IV on day +3 and +4, followed by TK, initiated at a dose of 0.03/kg/24h IV on day +5 and titrated to achieve a therapeutic level of 5-15mg/mL. Other GvHD prophylaxes combined calcineurine inhibitors combined with methotrexate, mycophenolate mofetil, or sirolimus, and anti-thymocyte globulin was added especially when MMUD were selected. Data were collected retrospectively and updated in June 2021. Overall survival (OS) and GvHD-Free/Relapsed free survival (GRFS) were considered the main outcome variables, and the cumulative incidence of GvHD was calculated accounting relapse and dead as competing events. In order to analyze the independent impact of PTCy-TK prophylaxis on OS and GRFS, a multivariate Cox regression analysis was performed including GvHD prophylaxis, Disease Risk Index, and transplant year (dichotomized with a cut-off in 2017, given the marked increase of PTCy-TK after this year) as explanatory variables together with other variables with prognostic value in the univariate analysis. RESULTS Baseline characteristics of patients classified according to the GvHD prophylaxis are reported in Figure 1. The two cohorts of patients according to GvHD prophylaxis are well balanced. Peripheral blood was the predominant stem cell source in the vast majority (97%). Of note, 53 out of 72 patients receiving PTCy-TK were transplanted between July 2017 and December 2020. And UD was used in more than 90% of PTCy-TK alloHCT, compared to 44% of alloHCT with other prophylaxes. The median of days for neutrophil (20 vs 16, p&lt;0.01) and platelet (19 vs 11, p&lt;0.01) engraftment were higher for patients receiving PTCy-TK, while the differences between the incidences of viral reactivations and infections were not statistically significant between the two groups. The cumulative incidence of grade II-IV aGvHD (day +100: 21.9% vs 21.5%, p=0.88) and grade III-IV aGvHD (day +100: 9.2% vs 9.3%, p=0.88) were comparable between both cohorts, but the use of PTCY-TK resulted on a significant reduction on the incidence of moderate/severe cGvHD (1-y: 9% vs 31.5%, p&lt;0.01) (Figure 1). OS (1-y: 72.1% vs 66.7%, HR 0.98; p=0.91), NRM (1-y: 18.1% vs 13.3%, HR 1.20; p=0.63), and relapse rates (1-y: 18.1% vs 22.9%, HR 0.86, P=0.65) were similar in both groups (PTCy-TK and other GvHD prophylaxis, respectively). However, PTCy-TK significantly resulted into an improved GRFS (1-y: 52.6% vs 30.7%, HR 1.68, p=0.01). A multivariate analysis confirmed the independent favorable impact of PTCy-TK prophylaxis on GRFS (HR 0.58, p=0.01), but not on OS (Figure 1). CONCLUSIONS PTCy-TK, alone, is an effective GVHD prophylaxis for alloHCT when related and UD are selected. The use of this innovative combination provides superior GRFS than the use of conventional GvHD prophylaxis in older adults undergoing alloHCT, with comparable transplant-related mortality and relapse rates. GRFS is a composite endpoint considered a surrogate outcome of health-related quality of life, and the improvement of this parameter is remarkable in PTCy-TK alloHCT, especially for older patients. Figure 1 Figure 1. Disclosures Lozano: Grifols: Honoraria; Terumo BCT: Honoraria, Research Funding; Macopharma: Research Funding. Rosinol: Janssen, Celgene, Amgen and Takeda: Honoraria. Esteve: Novartis: Consultancy, Research Funding; Abbvie: Consultancy; Astellas: Consultancy; Jazz: Consultancy; Novartis: Research Funding; Pfizer: Consultancy; Bristol Myers Squibb/Celgene: Consultancy.

scholarly journals Post-Transplant Cyclophosphamide for Gvhd Prophylaxis in Matched Unrelated Donor Transplantation Compared to ATG-Based Prophylaxis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3285-3285
Author(s):  
Rebeca Bailén ◽  
Mi Kwon ◽  
Maria Jesus Pascual-Cascon ◽  
Anna Torrent ◽  
Christelle M Ferra ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Cumulative Incidence ◽  
High Dose ◽  
Unrelated Donor ◽  
Matched Unrelated Donor ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis

Background: Post-transplant high dose cyclophosphamide (PT-CY) effectively prevents graft-versus-host disease (GVHD) after unmanipulated HLA-haploidentical hematopoietic stem cell transplantation (HSCT). The use of PT-CY in HLA-identical donor is less explored. In this study, we analyzed the results of PT-CY for GVHD prophylaxis in matched unrelated donor (MUD) HSCT and compared them with those obtained after prophylaxis with anti-thymocyte globulin (ATG), methotrexate (MTX) and cyclosporine (CsA). Methods: 132 matched unrelated donor HSCT from 4 Spanish centers have been analyzed: 60 performed between 2010 and 2018 using ATG-MTX-CsA and 72 performed between 2014 and 2018 using PT-CY. Results: Baseline characteristics and post-transplant complications are shown in Table 1. Peripheral blood was used as graft source in 92% of the patients in the ATG group and in 78% in the PT-CY group. GVHD prophylaxis consisted in rabbit ATG either 2mg/kg days -4 to -2 (41 patients, 68%) or 0.5mg/m2 on day -3 followed by 1mg/kg days -2 and -3 (19 patients, 32%), MTX days +1, +3, +6 and +11, and CsA from day -1 in the ATG group. The PT-CY group received cyclophosphamide 50 mg/kg/d on days +3 and +4, followed by either CsA or tacrolimus plus mycophenolate mofetil (MMF) from day +5 in 30 patients (42%), or cyclophosphamide on days +3 and +5 combined with CsA or tacrolimus in 42 patients (58%; 16 out of them also received sirolimus due to 9/10 HLA-match). Cumulative incidence of grade II-IV (67% vs 46%, p=0.008) and III-IV (34% vs 3%, p=0.003) acute GVHD, were significantly higher in the ATG group (Figure 1). There were no differences in the 2-year cumulative incidence of chronic moderate to severe GVHD (23% vs 24%, p=0.86). After a median follow-up of 78 months for the ATG group and 26 months for the PT-CY group, no differences were found in the 2-year overall survival (58% vs 60%, p=0.475), 2-year event-free survival (51% vs 50%, p=0.961) and the composite endpoint of GVHD-free and relapse-free survival (44% vs 40%, p=0.742). The 2-year cumulative incidence of relapse (22% vs 26%, p=0.67) and non-relapse mortality (NRM) (24% vs 22%, p=0.68) were also similar between both groups. However, NRM in the ATG group was due to GVHD in 9 out of 16 patients, while in the PT-CY group NRM was mostly due to infections and organ toxicity and only 3 out of 15 patients died due to GVHD. The incidence of sinusoidal obstruction syndrome was low in both groups (0% vs 4%, p=0.11). CMV reactivation rates were similar (40% vs 51%, p=0.191). However, both hemorrhagic cystitis and EBV reactivation were higher in the ATG group (56% vs 12%, p=0.00, and 5% vs 0%, p=0.05, respectively). Conclusions: In our experience, GVHD prophylaxis using PT-CY combined with additional immunosuppression after MUD HSCT, using mostly peripheral blood as graft source, resulted in lower incidence of aGVHD compared to prophylaxis based on ATG-MTX-CsA. Although no impact on non-relapse mortality was observed, GVHD associated mortality was higher in the ATG group as well as cystitis and EBV reactivations. Prospective studies with longer follow-up are needed to confirm these observations. Disclosures No relevant conflicts of interest to declare.

scholarly journals Post-Transplant Cyclophosphamide Versus MTX-CSA As Gvhd Prophylaxis in HLA-Identical Sibling HSCT

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3394-3394
Author(s):  
Rebeca Bailén ◽  
Maria-Jesús Pascual ◽  
Pascual Balsalobre ◽  
Anabel Gallardo-Morillo ◽  
Abel García-Sola ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis

Abstract Background: Post-transplant high dose cyclophosphamide (PT-CY) effectively prevents graft-versus-host disease (GVHD) after HLA-haploidentical hematopoietic stem cell transplantation (HSCT). However, the use of PT-CY in HLA-identical HSCT is less explored. In this study, we analyzed the results of PT-CY as GVHD prophylaxis in HLA-identical sibling HSCT and compared them with those obtained after prophylaxis with methotrexate (MTX) plus cyclosporine (CsA). Methods: 107 HLA-identical sibling (10/10) HSCT from 2 Spanish centers have been analyzed: 50 performed consecutively between 2010 and 2015 using MTX-CsA as GVHD prophylaxis, and 57 performed consecutively between 2014 and 2018 using PT-CY. Results: Baseline characteristics and post-transplant complications are shown in Table 1. GVHD prophylaxis consisted in MTX days +1, +3, +6 and +11, and CsA from day -1 in the MTX-CsA group. The PT-CY group received cyclophosphamide 50 mg/kg/d on days +3 and +5 in 38 patients (65%), combined with CsA from day +5, and cyclophosphamide on days +3 and +4 in 19 patients (35%), followed by CsA and mycophenolate mofetil from day +5. Graft source was PBSC in 96% in the MTX-CsA group and 86% in the PT-CY group. Conditioning regimen was myeloablative in 64% and 40%, respectively. Neutrophil and platelet engraftment was significantly delayed in the PT-CY group (14.5 (11-27) vs 15.5 (13-37), p=0.02; 11.5 (8-180) vs 20.5 (10-43), p=0.02). After a median follow-up of 60 months for the MTX-CsA group and 15 months for the PT-CY group, 2-year overall survival (OS) was 56% (42-70) and 78% (67-90) (p=0.088), and event-free survival (EFS) was 48% (34-62) and 62.5% (42.5-82.5) (p=0.054), respectively. Cumulative incidence at 100 days of grade II-IV (52.2% vs. 22.6%, p=0.0015), and III-IV (24.4% vs. 8.8%, p=0.016) acute GVHD were significantly higher in the MTX-CsA group (Figure 1A). No differences were observed in the 2-year cumulative incidence of chronic moderate to severe GVHD (26% vs. 16.7% (p=0.306)). No differences were observed in the 2-years cumulative incidence of relapse (27% vs. 28% (p=0.47)). Non-relapse mortality (NRM) at 2-years showed a higher trend in the MTX-CsA cohort (24% vs. 8.8%, p=0.054). Finally, the composite endpoint of GVHD and relapse-free survival (GRFS) at 2-years was significantly better in the PT-CY group (48% vs. 24%, p=0.011) (Figure 1B). Conclusions: In our experience, GVHD prophylaxis using PT-CY combined with additional immunosuppression after HLA-identical sibling HSCT, using mostly peripheral blood as graft source, reduced the cumulative incidence of acute GVHD compared to standard prophylaxis with MTX-CsA, leading to an impact on GRFS. To our knowledge, this is the largest comparative retrospective cohort reported. Further prospective studies with longer follow-up are needed to confirm these observations. Disclosures No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplantation with Intermediate Conditioning Is Effective in High Risk Relapse and Progressive Disease of Aggressive Non-Hodgkin-Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3379-3379 ◽  
Author(s):  
Bertram Glass ◽  
Justin Hasenkamp ◽  
Anke Goerlitz ◽  
Peter Dreger ◽  
Joerg Schubert ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Research Funding ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Myeloablative Conditioning ◽  
Early Relapse ◽  
Gvhd Prophylaxis ◽  
Unrelated Donors

Abstract Abstract 3379 Poster Board III-267 Background: Allogeneic stem cell transplantation ( SCT ) is increasingly being used to treat relapsed lymphoma. We reasoned that patients with high – risk ( chemorefractory disease, short time interval between first – line therapy and relapse ) aggressive lymphoma need vigorous debulking ( myeloablative conditioning ) and a strong GvLymphoma effect (early T–cells transferred with the graft: Glass et al., BMT 2004 ) ) in order to obtain optimal results Patients and Methods: Younger patients ( 18 to 65 yrs ) with aggressive NHL and primary progressive disease, early relapse with at least one IPI risk factor, or relapse after HDT /ASCT were included into the study. They received myeloablative conditioning (Fludarabine 125 mg/m2, Busulfan 12 mg/kg and cyclophosphamide 120 mg/kg) followed by GVHD prophylaxis with short term mycophenolat mofetil plus tacrolimus. After an amendment in July 2008 anti-thymocyte globulin (ATG) was given to all patients prior to transplantation. Patients were randomized to receive two courses of rituximab ( 4 × 375 mg/ m2) post transplant starting on day +21 and day +175 or no additional GVHD prophylaxis. From June 2004 to July 2009, 84 patients with aggressive NHL were enrolled and 81 were eligible for toxicity analysis (median age 49 years). 71 patients had follow up allowing for a meaningful survival analysis. Forty - one pts had diffuse large B cell NHL, 6 patients follicular lymphoma grade 3, 8 pts blastic mantle cell lymphoma, 2 pts aggressive marginal zone lymphoma, 4 patients lymphoblastic B cell lymphoma, and 20 pts suffered from T cell lymphoma. Forty-five (54%) pts received at least one cycle of HDT and autologous SCT prior to alloSCT; 75% had early relapse (< 12 months) or primary progressive disease, 59% chemo-refractory disease and 24% had progressive disease with high or high intermediate age adjusted IPI immediately prior to conditioning. Mobilized blood was obtained from HLA-identical siblings in 24 pts, from matched unrelated donors in 40 pts and from one locus mismatched unrelated donors in 17 pts. Fifty – five patients did receive ATG. Median observation time of surviving patients is 1.9 years. Forty – one pts died, in 26 patients death was treatment related. After one year, estimated overall survival is 52% (95% CI 39% to 63%), progression free survival is 46% (95% CI 33% to 57%), relapse rate is 29% (95% CI 43% to 10%), non relapse mortality is 37% (95% CI 26% to 50%). The incidence of acute GVHD > grade 1 is 66% (95% CI 49% to 82%). The last documented lymphoma progress occurred at day 288 after alloSCT. Patients with high-intermediate or high IPI at transplant did not differ significantly in PFS from patients with low and low-intermediate IPI (PFS at 2 years 34% vs 41%, p=0.144). There are no significant differences in OS, PFS and GvHD for pts receiving Rituximab or not. Conclusion: This alternative myeloablative conditioning followed by T - replete allogeneic SCT is an effective treatment option in patients with high risk features like active disease at transplantation and high – tumor burden. Although the incidences of GVHD ( uninfluenced by the administration of Rituximab ) and non-relapse mortality were relatively high, relapse rates were low and OS and EFS are promising While further optimization of conditioning by using lymphoma – specific drugs in high doses and improvement of GvHD – prophylaxis by adding optimal doses of ATG are certainly possible we do not believe that minimal conditioning and in vivo T – cell depletion will cure patients with high – risk aggressive lymphoma. Disclosures: Glass: Roche: Honoraria, Research Funding. Off Label Use: Rituximab will be used as prophylaxis for graft-versus-host-disease. Schmitz:Roche: Honoraria, Research Funding.

scholarly journals Post-transplant cyclophosphamide containing regimens after matched sibling, matched unrelated and haploidentical donor transplants in patients with acute lymphoblastic leukemia in first complete remission, a comparative study of the ALWP of the EBMT

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Jaime Sanz ◽  
Jacques-Emmanuel Galimard ◽  
Myriam Labopin ◽  
Boris Afanasyev ◽  
Moiseev Ivan Sergeevich ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Cumulative Incidence ◽  
Lymphoblastic Leukemia ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Donor Type ◽  
Matched Sibling ◽  
The Impact

Abstract Background There is no information on the impact of donor type in allogeneic hematopoietic stem cell transplantation (HCT) using homogeneous graft-versus-host (GVHD) prophylaxis with post-transplant cyclophosphamide (PTCy) in acute lymphoblastic leukemia (ALL). Methods We retrospectively analyzed outcomes of adult patients with ALL in CR1 that had received HCT with PTCy as GVHD prophylaxis from HLA-matched sibling (MSD) (n = 78), matched unrelated (MUD) (n = 94) and haploidentical family (Haplo) (n = 297) donors registered in the EBMT database between 2010 and 2018. The median follow-up period of the entire cohort was 2.2 years. Results Median age of patients was 38 years (range 18–76). Compared to MSD and MUD, Haplo patients received peripheral blood less frequently. For Haplo, MUD, and MSD, the cumulative incidence of 100-day acute GVHD grade II–IV and III–IV, and 2-year chronic and extensive chronic GVHD were 32%, 41%, and 34% (p = 0.4); 13%, 15%, and 15% (p = 0.8); 35%, 50%, and 42% (p = 0.01); and 11%, 17%, and 21% (p = 0.2), respectively. At 2 years, the cumulative incidence of relapse and non-relapse mortality was 20%, 20%, and 28% (p = 0.8); and 21%, 18%, and 21% (p = 0.8) for Haplo, MUD, and MSD, respectively. The leukemia-free survival, overall survival and GVHD-free, relapse-free survival for Haplo, MUD, and MSD was 59%, 62%, and 51% (p = 0.8); 66%, 69%, and 62% (p = 0.8); and 46%, 44%, and 35% (p = 0.9), respectively. On multivariable analysis, transplant outcomes did not differ significantly between donor types. TBI-based conditioning was associated with better LFS. Conclusions Donor type did not significantly affect transplant outcome in patient with ALL receiving SCT with PTCy.

scholarly journals GVHD Prophylaxis with Post-Transplant High Dose Cyclophosphamide: Impact on Engraftment, Treatment-Related Mortality and Resource Utilization

2016 ◽  
Vol 22 (3) ◽  
pp. S397-S398
Author(s):  
Nasheed Mohammad Hossain ◽  
Patricia Lamont Kropf ◽  
Stefan Klaus Barta ◽  
Mary Ellen Martin ◽  
John Ulicny ◽  
...  
Keyword(s):  
Resource Utilization ◽  
High Dose ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Treatment Related Mortality ◽  
Related Mortality

High-dose chemotherapy for relapsed and refractory diffuse large B-cell lymphoma: mediastinal localization predicts for a favorable outcome.

1998 ◽  
Vol 16 (1) ◽  
pp. 63-69 ◽  
Author(s):  
U Popat ◽  
D Przepiork ◽  
R Champlin ◽  
W Pugh ◽  
K Amin ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Disease Free Survival ◽  
Large Cell ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Free Survival ◽  
Ann Arbor ◽  
Large Cell Lymphoma ◽  
Disease Free

PURPOSE This study was performed to evaluate the outcome of high-dose chemotherapy and autologous transplantation in patients with diffuse B-cell large-cell lymphoma, and, specifically, to evaluate the impact of primary mediastinal localization on the outcome of high-dose chemotherapy. PATIENTS AND METHODS A retrospective review was performed of all patients with diffuse large B-cell lymphoma who underwent autologous marrow or peripheral-blood stem-cell transplantation at our institution between January 1 986 and December 1995. RESULTS Ninety patients were identified, of whom 31 (34%) had a primary mediastinal B-cell large-cell lymphoma (PML). Cumulative probabilities of disease-free survival, overall survival, and disease progression are 40% (95% confidence interval [CI], 29 to 51), 42% (95% CI, 31 to 53), and 52% (95% CI, 40 to 64), respectively. By univariate analysis, low lactate dehydrogenase (LDH) level and low Ann Arbor stage at transplant were associated with improved survival and disease-free survival. There was a trend for improved disease-free survival and survival for patients with PML. Multivariate stepwise Cox regression analysis showed that LDH level, Ann Arbor stage, and primary mediastinal localization were independent favorable prognostic factors for disease-free survival and survival. LDH level and Ann Arbor stage were also predictive for the risk of disease progression. CONCLUSION Our results indicate that patients with PML may display an increased susceptibility to high-dose chemotherapy compared with other types of B-cell large-cell lymphoma. These findings, if confirmed, may have implications for the initial management of patients with PML.

scholarly journals Post-Transplant Cyclophosphamide and Thymoglobulin, a Graft-Versus-Host Disease Prophylaxis in Matched Sibling Donor Peripheral Blood Stem Cell Transplantations

2020 ◽  
Vol 29 ◽  
pp. 096368972096590
Author(s):  
Chutima Kunacheewa ◽  
Weerapat Owattanapanish ◽  
Chutirat Jirabanditsakul ◽  
Surapol Issaragrisil
Keyword(s):  
Stem Cell ◽  
Graft Versus Host Disease ◽  
Peripheral Blood ◽  
Chronic Gvhd ◽  
Survival Rates ◽  
Free Survival ◽  
Graft Versus Host ◽  
Post Transplant ◽  
Gvhd Prophylaxis ◽  
Matched Sibling

Post-transplant cyclophosphamide (PTCy) has been explored in several types of stem cell transplantations (SCTs) and it proved highly effective in controlling graft-versus-host disease (GvHD) without aggravating relapsed disease. However, PTCy alone has resulted in inferior outcomes in matched sibling donor (MSD) employing peripheral blood (PB) SCTs. We hypothesized that adding thymoglobulin to PTCy would be able to control GvHD effectively. We retrospectively compared the use of standard GvHD prophylaxis encompassing a combination of PTCy and thymoglobulin (ATG) in patients with myeloid malignancies in a myeloablative conditioning MSD PBSCT. Forty-two patients underwent PBSCT using either methotrexate and cyclosporine (MTX/CSA, 21 patients) or PTCy and ATG (21 patients) as a GvHD prophylaxis. With median follow-ups of 71 months, the 1-year GvHD-free, relapse-free survival rates and chronic GvHD-free survival rate of the standard and PTCy/ATG groups were similar: 24% versus 37% ( P = 0.251) and 29% versus 43% ( P = 0.095), respectively. When focusing on chronic GvHD we observed that 17/35 patients (48.6%) suffered from this, 5/18 (27.8%) treated with MTX/CSA had extensive chronic GvHD, but 0/17 PTCy/ATG did. Twenty-one patients required additional GvHD treatment; 7/21 in the PTCy/ATG received only corticosteroid, while 8/14 MTX/CSA required at least 2 drugs. The 5-year overall survival rates were 52% and 52% ( P = 0.859), and the 5-year disease-free survival rates were 52% and 52% ( P = 0.862) for the MTX/CSA and PTCy/ATG groups, respectively. We conclude that PTCy in combination with ATG without immunosuppression of a calcineurin inhibitor can effectively control GvHD.

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