A “Single” Dose of G-CSF after Autologous Stem Cell Transplantation in Patients with Malignant Lymphoma - Third Interim Analysis of Multicentre Randomized Trial Comparing Standard Schedule with Delayed Application and Placebo.

Abstract The optimal schedule of G-CSF given after autologous peripheral stem cell transplantation (ASCT) has not been defined yet. Here we present results of the third interim analysis of randomized multicentre trial comparing standard application of G-CSF from day +5 (arm A) with delayed dosing (G-CSF was started when WBC reached 0,5x109/l and neutrophil count 0,1x109/l; arm B) and placebo (arm C). In order to eliminate the influence of diagnosis and conditioning and to minimize the impact of graft quality only patients with malignant lymphoma conditioned by BEAM and with graft harvested in maximum 3 aphereses containing at least 5,0x106 CD 34+cells/kg were included. Patients signed informed consent before registration into the study that had been approved by local ethical and national health care authorities. 115 patients at median age 45 (range 21 – 64) were randomized by July 15th, 2004. The data of 97 patients were analysed. There was no difference in age, lymphoma bone marrow involvement at diagnosis, number of chemotherapy cycles and the use of radiotherapy before transplantation and CD 34+ cells content in graft between any two of the three arms. Duration of neutropenia below 0,5x109/l and 1,0x109/l and number of days to neutrophil engraftment over 0,5x109/l and 1,0x109/l are listed in the table. A significant difference in duration of neutropenia and time to neutrophil engraftment was found between the arms A and B (p=0,002 – 0,005), the arms A and C (p<0,0001) and also between the arms B and C (p=0,04–0,0001). A trend for delayed platelet engraftment was observed in both arms with G-CSF (A and B). Duration of hospitalisation was significantly longer in placebo group (arm C), however, there was no prolongation of fever or antibiotic use. The delayed „single” application of G-CSF (usually with one or two doses sufficient for full neutrophil recovery) appears to be safe and cost effective. Comparing with standard G-CSF schedule only one day delay in median neutrophil engraftment was observed. We hope to finish the study within the year 2004. Supported by the grant MSN 15110004. Arm A / G-CSF from day +5 (n=33) Arm B / Tailored initiation of G-CSF (n=32) Arm C / Placebo (n=32) * median(range) Days with neutropenia <0,5x109/l (days) 7 (4–10)* 8 (6–11)* 10 (6–30)* Days with neutropenia <1,0x109/l (days) 8 (5–15)* 9 (7–11)* 11,5 (6–30)* Neutrophil engraftment >0,5x109/l (day +) 10 (9–12)* 11 (9–15)* 14 (9–30)* Neutrophil engraftment >1,0x109/l (day +) 11 (9–22)* 12 (9–15)* 15 (10–30)* Platelet engraftment >20x109/l (day +) 12 (2–33)* 12 (7–30)* 11 (7–24)* Platelet engraftment >50x109/l (day +) 17,5 (8–100)* 16,5 (9–115)* 13 (8–32)*

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Different Outcome for Angioimmunoblastic T-Cell Lymphoma (AIL) and Peripheral T-Cell Lymphoma Unspecified (PTCL-U) Following Upfront Autologous Stem Cell Transplantation.

Blood ◽

10.1182/blood.v108.11.5431.5431 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5431-5431 ◽

Cited By ~ 2

Author(s):

Peter Reimer ◽

Thomas Ruediger ◽

Florian Weissinger ◽

Hans Konrad Mueller-Hermelink ◽

Andreas Engert ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

T Cell Lymphoma ◽

Angioimmunoblastic T Cell Lymphoma ◽

The Impact

Abstract Introduction: Peripheral T-cell lymphomas (PTCL) are rare diseases and optimal treatment strategies still remain to be defined. With the exception of the ALK-positive anaplastic large cell lymphoma (ALCL) that shows a favourable outcome following conventional chemotherapy, PTCL are known for their poorer prognosis compared to aggressive B-cell lymphomas. However, the impact of the different PTCL-subtypes on treatment outcome has not been clearly demonstrated in prospective studies. PTCL unspecified (PTCL-U) and angioimmunoblastic T-cell lymphoma (AIL) represent the most common subtypes of PTCL in Western countries, accounting for approximately 70% of PTCL. We therefore analysed the data of our study on myeloablative radiochemotherapy followed by autologous stem cell transplantation (ASCT) in primary diagnosed PTCL with regard to the main histologic subtypes. Material and Methods: From 06/00 to 06/06 92 patients with confirmed diagnosis of PTCL entered the study. Primary cutaneous PTCL and ALK+ ALCL were excluded from the trial. Main subtypes were PTCL-U (n= 37) and AIL (n= 28) accounting for 65 of the 92 patients (71%). 0f these patients 53 (PTCL, n= 31; AIL, n= 22) were evaluable for the analysis (82%). Results: Median age was 50 years in the PTCL-U and 47.5 years in the AIL group, respectively. The International Prognostic Index (IPI) did not differ in both groups. In the PTCL-U and the AIL group a low/intermediate-low risk was found in 35% and 36%, respectively and a high/intermediate-high risk in 65% and 64%, respectively. There were slightly more patients in stage IV in the AIL group compared to the PTCL-U group (64% versus 53%). In addition, more patients in the AIL group complained of B-symptoms and had bone marrow involvement compared to the PTCL-U group (86% versus 66% and 48% versus 39%, respectively). However, in an intent-to treat analysis only 58% in the PTCL-U group compared to 82% in the AIL group underwent ASCT mainly due to a higher rate of patients with progressive disease in the PTCL-U group. The median overall survival (OS) was 11 months in the PTCL-NOS and 20 months in the AIL group. Regarding only patients undergoing ASCT, the median OS was 13.5 months in the PTCL-U and 25.5 months in the AIL group. Conclusion: Our analysis suggests that patients with AIL, although showing a slightly more unfavourable risk profile at diagnosis, benefit more from upfront autotransplantation than patients with PTCL-U in our study.

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Impact of the New Anti-Myeloma Drugs on Outcome of Allogeneic Stem-Cell Transplantation with Reduced-Intensity Conditioning in Patients with High-Risk Multiple Myeloma

Blood ◽

10.1182/blood.v118.21.4456.4456 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4456-4456

Author(s):

Jean El-Cheikh ◽

Roberto Crocchiolo ◽

Jean Marie Boher ◽

Sabine Furst ◽

Anne Marie Stoppa ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Reduced Intensity Conditioning ◽

Free Survival ◽

Graft Versus Host ◽

Significant Difference ◽

The Impact ◽

Reduced Intensity

Abstract Abstract 4456 The increasing use of the novel agents, lenalinomide and bortezomib, in the treatment of multiple myeloma (MM) has contributed to higher complete remission (CR) rates and longer overall (OS) and event free survival (EFS). We assessed the impact of these drugs on the outcome of high-risk MM patients treated with allogeneic stem-cell transplantation (allo-SCT) after reduced-intensity conditioning (RIC) over the last 10 years in our program. This retrospective study compared 45 patients (group1) transplanted in our centre between January 1999 and January 2006 and who had not received either novel agent prior to transplant (as induction or relapse therapy) with 34 patients (group 2) transplanted between January 2006 and June 2010 who received either one or both drugs before allo-SCT. The median time between diagnosis and Allo-SCT was 37 months (6–161) and 41 months (9–145) in the two groups respectively (p=NS). The median time between auto-SCT and allo-SCT was 9 months (2–89) and 27 months (2–49) respectively (p<0.0001). 36 patients (80%) in the first group vs. 8 patients (24%) in the second group received a tandem auto allo-SCT (p<0.0001). The disease status at transplantation was in CR in 2 patients (4%) vs. 10 patients (29%) and PR or stable disease in 35 patients (78%) vs. 21 patients (62%) in the first and the second group respectively (p<0.0033). in the table 1 we resumed some important data. Table 1Table 1:Patients Characteristic:Characteristics n=791999-2006 n=45 (57%)2006-2010 n=34 (43%)Fisher, p valueMedian age years (range)51 (27-65)55 (39-67)Number of prior therapies 1 2318 (40) 17 (38) 10 (22)8 (24) 18 (52) 8 (24)0.1509Cytogenetics at diagnosis Normal Del(13) Del (17) t (4;14) NA5 (11) 4 (9) 36 (80)3 (9) 12 (35) 19 (56)0.00504Disease status CR ou VGPR PR ou SD PD or refractory2 (4) 35 (78) 8 (18)10 (29) 21 (62) 3 (9)0.003359Donor type Matched Sibling Unrelated Donor45 (100) 021 (62) 13 (38)0.0004517Conditioning treatment With TBI With ATG19 (42) 26 (58)9 (26) 25 (74)0.1632Legend: Allo-SCT, allogeneic stem cell transplantation; Auto-SCT, autologous stem cell transplantation; CR, complete response; VGPR, very good partial response; PR, partial response; SD, stable disease; PD, progressive disease. GVHD indicates graft-versus-host disease; CSP, cyclosporine; MMF, mycofenolate mofetyl; TBI, total-body irradiation; ATG, anti-thymoglobulin; TRM, Transplant related mortality. Groups differ in several aspects: In recent years allogeneic transplant was considered rather as salvage therapy in patients relapsing after auto-SCT than in a tandem auto-allo strategy, patients with cytogenetic aberrations (p<0.005), and stem cell source from unrelated donor (13 patients (38%) vs. none) (p<0.0004), and two days of anti-thymoglobuline (ATG 2,5mg/kg/day). (P<0.001), in the second group. Table 1 The median follow-up after transplant was 45 (2–127) and 16 (3–39) months in the first and second group respectively (p<0.001). The cumulative incidence of acute graft versus-host disease (GVHD) tended to be higher before 2006 (47% vs. 24%; p=0.0584). The cumulative incidence of chronic GVHD was statistically different (56% vs. 30%; p=0.0241). The estimated probability of TRM at day 100 was 12% in the first group vs. 0 % in the second group (p=0.077) and did not differ between groups at 2 years. (18% vs. 23% (p =0.537)). The overall survival (OS) at two years was 60% vs 70% in the first and second group respectively (p=0.1784). The progression-free survival (PFS) tended to be different at 2 years (45% vs. 65% (p=0.056)). The median of PFS is 22 months for patients transplanted prior 2006 and is not reached in the second group (p=0.1811). In our study there was no significant difference in OS or TRM between the 2 groups in multivariate analysis; only the number of previous auto-SCT with more than two high dose chemotherapies has a negative impact on the OS. There was a significant difference in the incidence of relapse between the 2 groups in the multivariate analysis. Although we cannot carry out the impact of other changes related to our practice in the same period, these data suggests an impact in transplant outcomes of novel drugs introduced in the therapy of MM (lower TRM, GVHD and higher disease control). This piece of information, if confirmed, should be taken into considerations for present and future approaches. Disclosures: No relevant conflicts of interest to declare.

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Impact of Early Blast Clearance Following Induction Chemotherapy On the Outcome of Patients with Acute Myelod Leukemia Undergoing Allogeneic Stem Cell Transplantation in First Complete Remission

Blood ◽

10.1182/blood.v120.21.1998.1998 ◽

2012 ◽

Vol 120 (21) ◽

pp. 1998-1998

Author(s):

Philipp G. Hemmati ◽

Theis H. Terwey ◽

Philipp le Coutre ◽

Gero Massenkeil ◽

Bernd Dörken ◽

...

Keyword(s):

Stem Cell ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Induction Chemotherapy ◽

Allogeneic Stem Cell Transplantation ◽

High Dose ◽

Significant Difference ◽

The Impact ◽

First Complete Remission

Abstract Abstract 1998 Purpose: In patients with newly diagnosed acute myeloid leukemia (AML) rapid achievement of remission by induction chemotherapy is an important predictor for long-term disease control. In turn, patients who fail to attain early blast clearance after the first chemotherapy course have an inferior outcome. Here, we investigated the impact of early blast clearance on the overall outcome of patients with AML undergoing allogeneic stem cell transplantation (alloSCT) in first complete remission (CR1) as consolidation therapy. Patients and Methods: 169 (90 female, 79 male) patients with AML who underwent alloSCT in CR1 at our center between 1994 and 2011 were included. Data were prospectively recorded in our transplant data base and retrospectively analyzed as of December 31st, 2011. In detail, 107 patients (64%) had de novo AML, 31 patients (18%) had AML evolving from myelodysplastic syndrome (MDS), and 31 patients (18%) had therapy-related AML. According to the criteria of the SWOG/ECOG, cytogenetic risk was either favorable (6 patients, 4%), intermediate (104 patients, 62%), or poor (47 patients, 27%). Prior to alloSCT all patients were treated in a German multicenter AML trial and received at least two courses of induction chemotherapy, i.e. either standard “7+3” (daunorubicin 60 mg/m2, day 3–5 and Ara-C 100 mg/m2, day 1–7) or a “high-dose Ara-C” containing regimen (Ara-C 1–3 g/m2). In 98 patients (58%) induction chemotherapy resulted in blast clearance after the first course, whereas 71 patients (42%) failed to achieve early remission, but entered remission after 1 or 2 subsequent courses. Median age at transplantation was 47 years (range: 17–69 years). In 146 patients (86%) alloSCT was performed using peripheral blood stem cells (PBSCs), whereas 23 patients (14%) received a bone marrow (BM) graft. Conditioning consisted of standard myeloablative conditioning (MAC: 6 × 2 Gy TBI and 2 × 60 mg/m2 cyclophosphamide) in 81 patients (48%), whereas 86 patients (52%) received reduced intensity conditioning (RIC: busulfan 2 × 4 mg/kg, fludarabine 6 × 30 mg/m2 and ATG 4 × 10 mg/kg). A matched related donor was available in 82 patients (49%), whereas 68 patients (40%) or 19 patients (11%) were transplanted from a matched-unrelated or mismatched unrelated donor. Results: After a median follow-up of 45 months (range: 3–196 months) for the surviving patients, 91 patients (54%) are alive and in continuous remission. Causes of death were relapse in 38 patients (22%) or NRM in 33 patients (19%). At 1, 3 or 5 years projected overall survival (OS) was 72±6%, 58±6%, or 54±8% for all patients. Probability of relapse or non-relapse mortality (NRM) at 1, 3, and 5 years was 20±10% (20±11%), 31±12% (20±11%), and 34±12% (20±11%). Although there was no statistically significant difference in OS at 3 and 5 years between patients who achieved early blast clearance as compared to patients who failed to do so (p=0.09), disease-free survival (DFS) and probability of relapse differed significantly between the two groups at 3 years (77±8% vs 55±14%) or 5 years (75%±9% vs 52%±14%) following alloSCT (p=0.02). There was no significant difference in NRM between the two subgroups. Likewise, there was no statistically significant difference between patients conditioned with either MAC or RIC. In multivariate analysis cytogenetic risk group and remission status were identified as independent prognostic factors for DFS and probability of relapse. Conclusions: These results suggest that in patients with AML undergoing alloSCT in CR1 early blast clearance, i.e. following the first course of induction chemotherapy, predicts a very favorable outcome. Disclosures: No relevant conflicts of interest to declare.

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AL Amyloidosis: The Effect of Maintenance Therapy on Autologous Stem Cell Transplantation Outcomes

Journal of Clinical Medicine ◽

10.3390/jcm9113778 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3778

Author(s):

Michael Ozga ◽

Qiuhong Zhao ◽

Don Benson ◽

Patrick Elder ◽

Nita Williams ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Maintenance Therapy ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Prognostic Significance ◽

Al Amyloidosis ◽

Effective Treatment Option ◽

Significant Difference ◽

The Impact

Background: Autologous stem cell transplantation (ASCT) remains an effective treatment option for many patients with systemic light chain (AL) amyloidosis. While maintenance post ASCT in multiple myeloma is now standard, the decision to utilize maintenance in AL amyloidosis remains largely unexplored. The present study aims to determine the prognostic significance of utilizing maintenance therapy following ASCT and assess the impact of fluorescent in situ hybridization (FISH) abnormalities, bone marrow plasma cell burden (BMPC), and degree of organ involvement on this decision. Methods and results: This is a retrospective analysis of fifty AL amyloidosis patients who underwent ASCT at The Ohio State University. Twenty-eight patients received maintenance and twenty-two did not. Kaplan–Meier survival analysis was used to compare the effect of maintenance therapy with no significant difference in PFS (p = 0.66) and OS (p = 0.32) between the two groups. There was no difference in survival based on maintenance when further categorized by FISH, PFS (p = 0.15), and OS (p = 0.65); BMPC ≥ 10%, PFS (p = 0.49), and OS (p = 0.32); or with 2 or more organs involved, PFS (p = 0.34) and OS (p = 0.80). Conclusion: Maintenance therapy post ASCT did not impact PFS or OS when categorized by FISH abnormalities, increasing BMPC, or ≥2 organs involved in AL amyloidosis patients.

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Impact of Pre-Transplant Ruxolitinib in Myelofibrosis Patients on Outcome after Allogeneic Stem Cell Transplantation

Blood ◽

10.1182/blood.v128.22.1950.1950 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1950-1950

Author(s):

Sharifah Shahnaz Syed Abd Kadir ◽

Tatjana Zabelina ◽

Maximilian Christopeit ◽

Gerald G Wulf ◽

Eva Maria Wagner ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Unrelated Donor ◽

Spleen Size ◽

Peripheral Blood Stem Cells ◽

Significant Difference ◽

The Impact

Abstract Introduction Ruxolitinib is the first approved drug for treatment of myelofibrosis. Major effects are reduction in spleen size and improvement of constitutional symptoms. Because spleen size and constitutional symptoms may influence outcome after allogeneic stem cell transplantation (ASCT), ruxolitinib is recommended before stem cell transplantation in order to reduce therapy-related morbidity and mortality and improve outcome (EBMT/ELN recommendation, Leukemia 2015) The aim of this retrospective study was to evaluate the impact of pretreatment with ruxolitinib in comparison to transplantation of ruxolitinib-naïve MF patients with regard to outcome after ASCT. Patients and methods We included 171 myelofibrosis patients (pts) with a median age of 59 years (r: 28 - 74) who received ASCT between 2000 and 2015 from related (n = 25), matched (n=94) or mismatched (n=52) unrelated donor. Stem cell source were more peripheral blood stem cells (n = 167) than bone marrow (n = 4). All patients received busulfan-based reduced intensity conditioning. While 113 pts (66%) did not receive ruxolitinib, 58 pts (34%) received ruxolitinib at any time point prior to ASCT. The median daily dose of ruxolitinib was 30mg (range 10-40mg) and the median duration of treatment was 28 days (range 12-159 days). In 11 pts ruxolitinib was stopped before stem cell transplantation because of no response or loss of response, while in 35 pts ruxolitinib was given until start of conditioning and in 12 pts ruxolitinib was given until stable engraftment. GvHD prophylaxis consisted of CNI plus short course MTX or MMF and anti-lymphocyte globulin. According to dynamic IPSS (DIPSS) (n = 170) the patients were either low (n = 2), intermediate-1 (n = 37), intermediat-2 (n = 81), or high risk (n = 38). 74 patients (43%) were transfusion dependent. Results As the median follow up was shorter for patients treated with ruxolitinib (15 vs 73 months, p<0.001), we analyzed only 2 years RFS, OS, NRM and relapse incidence. Primary graft failure was seen in 2 pts in the ruxolitinib and 3 in the non-ruxolitinib group. The median leukocyte engraftment was 13 days (r., 9-32) in the ruxolitinib and 14 days (r., 7-34) in the non ruxolitinib group (p=0.7). The median age in the ruxolitinib group was slightly older ( 62 vs 58 years , p= 0.09). The incidence of acute GvHD grade I to IV was significantly lower in the ruxolitinib group (49% vs 64%, p=0.05), while aGvHD grade II-IV (33% vs 44%, p=0.14) and grade III/IV (23% vs 25%, p=0.48), did not differ significantly. The CI of NRM at 1 year was 18% (95% CI: 6-30%) for the ruxolitinib group and 22% (95% CI: 14-30%) for the non-ruxolitinib group (p=0.58), and the CI of relapse at 2 years was 8% (95% CI: 0-16%) vs 20% (95%CI: 12-28%, p=0.25). The 2 years RFS and OS was 66% (95%CI: 50-82%) and 69% (95%CI: 51-87) for the ruxolitinib group and 59% (95% CI: 49-69%) and 70% (95% CI:62-78%) for the non-ruxolitinib group (p=0.29 and p=0.45, respectively). Within the ruxolitinib group (n=53), 24 pts responded to ruxolitinib (more than 25% spleen size reduction), while 29 pts did not respond or lost response prior to stem cell transplantation. Here, no significant difference could be seen between the responding and non-responding group for NRM (19% vs 17%, p=0.69), Relapse (4% vs 13%, p=0.62), RFS (61% vs 72%, p=0.81) and OS (63% vs 75%, p=0.89). In a multivariate analysis including ruxolitinib treatment as variable there was a non-significant trend in favor for ruxolitinib pretreatment regarding NRM (HR 0.79; 95%CI: 0.38-1.66, p=0.54), relapse (HR 0.48; 95%CI: 0.18-1.31, p=0.15), RFS (HR 0.55; 95%CI: 0.29-1.03, p=0.06) and OS (HR 0.83; 95%CI: 0.41-1.67, p=0.61). Conclusions These results suggest that ruxolitinib pretreatment in myelofibrosis patient does not negatively influence outcome after allogeneic stem cell transplantation. To confirm the observed favorable trend in outcome after ruxolitinib treatment more patients and a longer follow-up is needed. Disclosures Crysandt: Novartis: Other: Travel grant. Stelljes:Pfizer: Consultancy. Kröger:Novartis: Honoraria, Research Funding.

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Influence of Fludarabine Pharmacokinetics on Outcome of Allogeneic Stem Cell Transplantation with Fludarabine-Busulfan Conditioning

Blood ◽

10.1182/blood.v126.23.3119.3119 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3119-3119

Author(s):

Mita Manna ◽

Andrew Daly ◽

Bill Kangarloo ◽

Mary Lynn Savoie ◽

Jan Storek

Keyword(s):

Overall Survival ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Clinical Outcomes ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Myeloablative Conditioning ◽

Dose Monitoring ◽

Significant Difference ◽

The Impact

Abstract Introduction Precise targeting of Busulfan dose has resulted in improved transplant outcomes following myeloablative conditioning with Fludarabine plus Busulfan (Flu-Bu). However, the impact of Fludarabine pharmacokinetics on outcomes in allogeneic stem cell transplantation (SCT) following myeloablative conditioning remains undefined. Methods A retrospective single-centre analysis was performed to evaluate the clinical outcomes of 88 patients who received Flu-Bu based conditioning. Patients received Flu (50mg/m2 days-6 to -2), Bu (3.2mg/kg days-5 to -2), and Total Body Irradiation (400 cGy in two doses on day-1). Busulfan dosing was adjusted to achieve a total exposure of 3750 μmol·min/L. Levels of the Fludarabine metabolite 9βD-arabinofuranosyl-2-fluoroadenosine were determined by high performance liquid chromatography-tandem mass spectrometry. Fludarabine exposure, expressed as Fludarabine area under the concentration-time curve (AUC), was calculated on patient blood samples collected on day-5. Results Median age of the 88 patients was 49 (range 18-65) years, and median creatinine clearance was 120.5mL/min (range 48-305mL/min). The most common transplanted hematologic malignancies included AML (31%), ALL (20%), and MDS (10%). 32 (36%) received their transplants from HLA-compatible siblings, and 56 (64%) from unrelated donors. Median plasma AUC was 9.038μg·h/mL (range 2.429 - 66.655μg·h/mL). When comparing patients with lower Flu exposure <9.000μg·h/mL versus those with higher Flu exposure >9.000μg·h/mL, there was no significant difference in grade II-IV acute Graft versus Host Disease (aGvHD; 25% versus 32%, p=0.27) or grade III-IV aGvHD (11% versus 14%, p=0.52). Furthermore, there was no difference in average days to engraftment (13.8 versus 13.9, 95% CI 13.01 - 14.72, p=0.77), or average number of infections in 1-year post transplant (2.3 versus 2.5, 95% CI 1.68 - 3.30, p=0.68). Transplant related mortality (TRM) at 100 days was not improved (7.0% versus 11.4%, p= 0.52) with AUC <9.000μg·h/mL. Progression free survival at 3 years with lower Flu exposure <9.000μg·h/mL was 68% (95%CI 53 - 79) compared to higher Flu exposure >9.000μg·h/mL at 59% (95% CI 45-73, p=0.70). Finally, there was no difference in overall survival (OS) at 12 months (Figure 1.0) in patients with an AUC <9.000μg·h/mL (73%, 95% CI 57-83) versus those with AUC >9.000μg·h/mL (73%, 95% CI 55-83, p-value 0.99). Conclusion In the setting of normal renal function, we have demonstrated that Fludarabine pharmacokinetics does not effect clinical outcomes in myeloablative allogeneic SCT. These data support no role for therapeutic dose monitoring and dose adjustment with Fludarabine in myeloablative conditioning regiments. Figure 1. Overall survival for patients 12 months after myeloablative SCT with Fludarabine AUC <9.000μg·h/mL compared to patients with Fludarabine AUC >9.000μg·h/mL. Figure 1. Overall survival for patients 12 months after myeloablative SCT with Fludarabine AUC <9.000μg·h/mL compared to patients with Fludarabine AUC >9.000μg·h/mL. Disclosures Off Label Use: Fludarabine in the use of myeloablative conditioning for allogeneic stem cell transplantation..

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Impact of prior JAK-inhibitor therapy with ruxolitinib on outcome after allogeneic hematopoietic stem cell transplantation for myelofibrosis: a study of the CMWP of EBMT

Leukemia ◽

10.1038/s41375-021-01276-4 ◽

2021 ◽

Author(s):

Nicolaus Kröger ◽

Giulia Sbianchi ◽

Tiarlan Sirait ◽

Christine Wolschke ◽

Dietrich Beelen ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Hematopoietic Stem ◽

Free Survival ◽

Significant Difference ◽

Pretreated Patients ◽

The Impact

AbstractJAK1/2 inhibitor ruxolitinib (RUX) is approved in patients with myelofibrosis but the impact of pretreatment with RUX on outcome after allogeneic hematopoietic stem cell transplantation (HSCT) remains to be determined. We evaluated the impact of RUX on outcome in 551 myelofibrosis patients who received HSCT without (n = 274) or with (n = 277) RUX pretreatment. The overall leukocyte engraftment on day 45 was 92% and significantly higher in RUX responsive patients than those who had no or lost response to RUX (94% vs. 85%, p = 0.05). The 1-year non-relapse mortality was 22% without significant difference between the arms. In a multivariate analysis (MVA) RUX pretreated patients with ongoing spleen response at transplant had a significantly lower risk of relapse (8.1% vs. 19.1%; p = 0.04)] and better 2-year event-free survival (68.9% vs. 53.7%; p = 0.02) in comparison to patients without RUX pretreatment. For overall survival the only significant factors were age > 58 years (p = 0.03) and HLA mismatch donor (p = 0.001). RUX prior to HSCT did not negatively impact outcome after transplantation and patients with ongoing spleen response at time of transplantation had best outcome.

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The Impact of Antithymocyte Globulin (ATG) Dose in Allogeneic Hematopoietic Stem Cell Transplantation with HLA Mismatched Donors

Blood ◽

10.1182/blood.v128.22.3393.3393 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3393-3393

Author(s):

Yunsuk Choi ◽

Ho Sup Lee ◽

Je-Hwan Lee ◽

Joon Ho Moon ◽

Ho-Jin Shin ◽

...

Keyword(s):

Stem Cell ◽

Hematopoietic Stem Cell Transplantation ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Hematopoietic Stem Cell ◽

Antithymocyte Globulin ◽

Chronic Gvhd ◽

Hematopoietic Stem ◽

Significant Difference ◽

The Impact

Abstract Background: Antithymocyte globulin (ATG) is usually included in conditioning regimens in hematopoietic stem cell transplantation (HSCT) from HLA mismatched donors to reduce the incidence of graft versus host disease (GVHD) and rejection. In this study, we intended to assess the clinical impact of ATG dose in HSCT from HLA mismatched donors. Patients and Methods: We retrospectively analyzed 268 consecutive patients with acute myeloid leukemia (n=159), acute lymphoblastic leukemia (n=49) or myelodysplastic syndrome (n=60) receiving busulfan based conditioning and HSCT with HLA mismatched sibling, unrelated, or haplo-identical family donors in five centers of Korea between 2005 and 2015. Results: The median age was 44.5 (range, 15-75) years. Fourty-two patients were treated with myeloablative conditioning and 226 patients with reduced intensity conditioning regimen. ATG at a total dose of 0 (n=31), 2.5-7.5 mg/kg (n = 16), 9 mg/kg (n = 164) or 12mg/kg (n=57) was given to patients according to protocol. 140 patients received HSCT in complete remission and 73 patients in relapse or refractory status. The median follow up duration for surviving patients was 33.8 (range, 2.0-100.6) months. The 3-year overall survival (OS) and event free survival (EFS) rate for all patients was 44.7% and 39.2% There was no significant difference of OS according to ATG dose (P=0.153), but ATG dose of 2.5-7.5mg/kg was significantly associated with better EFS than 0, 9 mg/kg, or 12mg/kg of ATG groups (79.1% vs. 45.4%, 38.9%, and 31.7%, respectively, P=0.038) (Table 1). In addition, ATG dose significantly affected on relapse (P=0.046). The relapse incidence in patients receiving 2.5-7.5 mg/kg of ATG was lower compared to those given 0, 9, or 12 mg/kg of ATG (6.7% for 2.5-7.5mg/kg of ATG group vs. 29.5%, 34.0%, and 46.9% for 0, 9, and 12 m/kg of ATG groups, respectively). The incidences of acute GVHD grades II-IV were 32.6%, 25.0%, 29.4% and 24.6% in patients receiving 0. 2.5-7.5, 9, and 12 mg/kg of ATG, respectively. The incidence of extensive chronic GVHD tended to be lower according to the increase of ATG dose (36.8%, 34.5%, 27.4%, and 21.1% for 0. 2.5-7.5, 9, and 12 mg/kg of ATG dose, respectively).In multivariate analysis, ATG dose of 9 mg/kg (P=0.023) and 12 mg/kg (P=0.036) was associated with shorter EFS compared to 2.5-7.5 mg/kg of ATG. Conclusion: 9mg/kg of ATG dose or more in HLA mismatched busulfan based HSCT with HLA mismatch donors increased the risk for relapse and reduced the EFS. Disclosures No relevant conflicts of interest to declare.

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Impact of CD3/T Regs Ratio in Donor Graft On Survival Rates in Allogeneic Peripheral Blood Stem Cell Transplantation

Blood ◽

10.1182/blood.v120.21.2030.2030 ◽

2012 ◽

Vol 120 (21) ◽

pp. 2030-2030

Author(s):

Mario Delia ◽

Domenico Pastore ◽

Anna Mestice ◽

Paola Carluccio ◽

Tommasina Perrone ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Relapse Rate ◽

Peripheral Blood ◽

Acute Gvhd ◽

Survival Rates ◽

Significant Difference ◽

Donor Graft ◽

The Impact

Abstract Abstract 2030 Background: The therapeutic efficacy of allogeneic stem cell transplantation (alloSCT) for hematological malignancies relies largely on the graft versus leukemia (GvL) effect exerted by the donor CD3 cells, but an uncontrolled graft-versus-host-disease (GvHD) bears a risk of complications. On the other hand, T regs cells (CD4+CD25high Foxp3+) are believed to maintain tolerance and to inhibit GvHD after alloSCT; also, the Foxp3 gene encodes a transcription factor that is a key for thymic development, so T regs cells could preserve an optimal microenviroment for the reconstitution of functional immunity after alloSCT. Moreover, when looking at post allotransplant patients' outcomes, while it is largely known the impact of acute GVHD (triggered by CD3 donor T cells) on survival, there is no evidence that donor graft CD3/T regs ratio may determine an effect in terms of OS, NRM and relapse free survival rates so far. Patients and Methods: In this study we analyzed the graft CD3+/Tregs ratio (gCD3/Tregs R) and determined its impact on acute GVHD (aGVHD), immunological recovery and survival rates (OS, NRM and Relapse) after myeloablative alloPBSCT. We analyzed 74 consecutive patients transplanted with unmanipulated peripheral blood stem cells from an HLA identical related donor (n=48) or an HLA identical unrelated donor (n=26); diagnoses were acute myeloid leukaemia (n=62), acute lymphoblastic leukaemia (n=13). The median CD3+ and Tregs dose administered was 238 (range (r): 67–550) and 12,5×106̂/Kg (r: 2–21), respectively; the median gCD3/Tregs R was 19 (r: 8–250). Patients were subdivided into a high gCD3/Tregs R (>=36) group (HR group n= 30) and a low gCD3/Tregs R (<36) (LR group n=44). Results: The incidence of aGVHD (grade II-IV) in the low gCD3/Tregs R (LR) group was lower than in the high gCD3/Tregs R (HR) group (4/30 or 13% vs 36/44 or 82%, p<.001). The OS, NRM and relapse rate at 3 years was 54,29 and 34%, respectively. Comparing LR with HR group a statistically significant difference is demonstrated for OS and NRM rates (65 vs 31%,p<.004; 3 vs 71%, p<.001), respectively, but not for the R one (35 vs 30%, p=ns). Comparing aGVHD+ with aGVHD- group OS, NRM and relapse were always statistically significant different (39 vs 65%,p<.005; 61 vs 7%,p<.001; 9 vs 53%,p<.002). Conclusions: Taken together, our data may suggest that Tregs content is able to mediate protective effects against aGVHD, while preserving GvL effects as demonstrated by relapse rate comparison between H and LR groups. However, larger studies are needed to understand the real contribution of gCD3/Tregs R on survival rates. Disclosures: No relevant conflicts of interest to declare.

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COVID-19 during Early Phase of Autologous Stem Cell Transplantation

Medicina ◽

10.3390/medicina57070724 ◽

2021 ◽

Vol 57 (7) ◽

pp. 724

Author(s):

Sławomir Milczarek ◽

Bartłomiej Baumert ◽

Anna Sobuś ◽

Ewa Wilk-Milczarek ◽

Krzysztof Sommerfeld ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Early Phase ◽

Hematopoietic Stem ◽

Prolonged Incubation ◽

Heavily Pretreated ◽

Engraftment Syndrome ◽

Interesting Correlation ◽

Neutrophil Engraftment

We present one of few cases of COVID-19 occurrence during the early phase of autologous hematopoietic stem cell transplantation. We observed an interesting correlation between the patient’s rapid clinical deterioration and myeloid reconstitution that cannot be assigned to engraftment syndrome. Our report emphasizes the need to investigate whether timely steroid therapy upon neutrophil engraftment in the setting of COVID-19 could limit the extent of lung injury and prevent ARDS. Furthermore, we discuss a significant issue of possible prolonged incubation of the virus in heavily pretreated hematological patients.

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