scholarly journals Donor Lymphocyte Infusions for Haematological Malignancy Relapse

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5775-5775
Author(s):  
Guillermo Orti ◽  
Irene García-Cadenas ◽  
Isabel Sánchez-Ortega ◽  
Mª Jose Jimenez ◽  
Laura Alonso ◽  
...  
Keyword(s):  
Total Dose ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Diagnosis ◽  
Time Interval ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Donor Lymphocyte Infusions

Abstract Donor lymphocyte infusions (DLI) are a therapeutic approach broadly used in relapse post Allogeneic Hematopoietic Cell Transplant (Allo-HCT). In CML relapse, DLI have proven very effective, but in other hematological malignancies its effectiveness has been reported rather erratic and poor; hence the need of a better understanding of factors influencing outcomes. Questions regarding the CD3 dose, the use of G-CSF mobilized DLI or the potential toxicity associated to the use of DLI from mismatched donors remain open. We report a cohort of 66 patients who, within a cell therapy program (Banc de Sang i Teixits, Barcelona), consecutively underwent allo-HCT and received DLI for relapse. Disease diagnosis was as follows: Lymphoproliferative malignancy (LPD) 29 patients AML and high-risk MDS 24 patients and ALL 13 patients (CML patients were not included). Median age at allo-HCT was 48 years (5-68). The combination female-donor and male-patient was 21%. 27% allo-HCT were T-cell depleted and 29% received a myeloablative conditioning regimen. Immunosupression was CsA-based in 83% of the allo-HCT. Transplants from HLA fully match donors were 54 (81%) and 19% were from mismatch donors. Indication for DLI was morphological relapse in 61 patients (92%) and disease detected by flow cytometer or at a molecular level in 5 patients (8%). 32 (48%) DLI were obtained at stem cell collection day (G-CSF mobilized) and cryopreserved, whereas 34 (52%) DLI were obtained by lymphapheresis. The median follow-up was 198 days (9-4246). The estimated 1-year OS was 60%. A total of 100 DLI were infused, with a median of 1.5 DLI/patient and a median time from allo-HCT to DLI of 303 days (70-5153). Median CD3+ total dose was 2x107 CD3+/Kg (first DLI median dose was 1x107 CD3+/Kg). The time interval from allo-HCT to DLI ≥10 months (Log-Rank 3.64, p=0.056) was associated to better survival. In line with this, there was a trend in patients relapsing ≥ 9 months post allo-HCT (median relapse date) for better survival (Log-Rank 3.33, p=0.068). Twenty-six patients (42%) developed GvHD post-DLI. In 17 patients overall grade was 2-4, which was not associated to poorer outcome. Lately, 8 patients developed extensive chronic GvHD. The development of chronic GvHD was associated to a better survival (Log-Rank 6.07, p=0.014). A total dose ≥1x107CD3+/Kg was associated to a better survival (Log-Rank 4.78, p=0.029) compared to total lower doses. The achievement of complete remission post DLI was also associated to better OS (Log-Rank 4.54, p=0.33). Ten patients died due to non-relapse mortality causes and twenty-seven due to disease progression. Of interest, we found a trend on outcomes when using non G-CSF mobilized DLI compared to-G-GCF mobilized DLI (Log-Rank 2.65, p= 0.104). However, the administration of a pre DLI debulky therapy was not associated with better outcomes. Variables with p<0.1 were included in the multivariate analysis, which identified the achievement of CR post DLI (p=025), chronic GvHD (p=0.026), total dose ≥1x107CD3+/Kg (p=0.026) and time from allo-HCT to DLI ≥10 months (p=0.026) associated to a better OS. Overall, this study reports a poor prognostic cohort, in which the vast majority had a post allo-HCT morphological relapse. In this group, patients treated with DLI can have a prolonged survival by achieving CR. Additionally, the survival appeared to be DLI dose-dependent, since patients receiving doses ≥1x107CD3+/Kg had better OS. Additionally, the development of chronic GvHD was associated to a better OS. Fig 1. OS according to the total CD3 dose infused Fig 2. OS according to the development of chronic GvHD Fig 3. OS according to the response post DLI. Disclosures No relevant conflicts of interest to declare.

scholarly journals Steroid-dependent acute GVHD after allogeneic hematopoietic cell transplantation: risk factors and clinical outcomes

2021 ◽  
Vol 5 (5) ◽  
pp. 1352-1359
Author(s):  
Najla El Jurdi ◽  
Ahmad Rayes ◽  
Margaret L. MacMillan ◽  
Shernan G. Holtan ◽  
Todd E. DeFor ◽  
...  
Keyword(s):  
Risk Factors ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Steroid Dependent ◽  
Steroid Sensitive

Abstract Acute graft-versus-host disease (aGVHD) has various risk factors and outcomes. We defined distinct aGVHD treatment response groups based on response to first-line corticosteroids: steroid sensitive (SS), steroid resistant (SR), and the rarely studied steroid dependent (SD) aGVHD. In 1143 consecutive adult and pediatric allogeneic hematopoietic cell transplant recipients, 385 (34%) developed aGVHD, with 10% having SS aGVHD, 9% SD aGVHD, and 14% SR aGVHD. The only factor significantly associated with SD in comparison with SS was older age (odds ratio [OR], 3.9; 95% confidence interval [CI], 1.4-11.3, when comparing 18- to 60-year-olds with &lt;18-year-olds). Factors significantly associated with SR in comparison with SS were unrelated donor (OR, 3.0; 95% CI, 1.2-7.4) and Minnesota high-risk aGVHD (OR, 2.4; 95% CI, 1.3-4.6). SR aGVHD was independently associated with higher risk for 2-year overall mortality (hazards ratio [HR], 1.8; 95% CI, 1.2-2.8) and nonrelapse mortality (NRM; HR, 2.1; 95% CI, 1.2-3.9). SS and SD GVHD groups had similar overall survival and NRM. The cumulative incidence of chronic GVHD was highest in the SD group, followed by the SR and SS groups (46%, 41%, and 29%, respectively). SD and SS GVHD had similar prognoses, both markedly better than those of the SR groups.

scholarly journals Pre-Salvage ISS and Other Important Outcome Predictors in CD34 Selected Allogeneic Hematopoietic Cell Transplant for Multiple Myeloma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3473-3473
Author(s):  
Adam Bryant ◽  
Patrick Hilden ◽  
Sergio Giralt ◽  
Miguel-Angel Perales ◽  
Guenther Koehne
Keyword(s):  
Multiple Myeloma ◽  
High Risk ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Older Age ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Term Survival ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
The Impact

Abstract Introduction Despite recent therapeutic advances Multiple Myeloma (MM) remains largely incurable, and outcomes in patients who develop resistance to imid or proteasome inhibitor therapies are universally dismal.1 Allogeneic hematopoietic cell transplant (alloHCT) remains the only curative MM treatment but has been associated with historically high rates of GVHD and of non-relapse mortality (NRM), exceeding 40% in some series.2 Although these rates have decreased in recent years, the potential morbidity and mortality associated with alloHCT and the increasing availability of alternative non-transplant therapies demands a thoroughly informed pre-alloHCT assessment. Here we assess the impact of pre-alloHCT variables on clinical outcomes in a large cohort of relapsed/refractory (RR) MM patients who underwent CD34+ selected alloHCT at our institution. Methods This retrospective study included all MM patients who had CD34+ selected alloHCT from Jun 2010 to Dec 2015. Patients were conditioned with targeted dose busulfan (0.8 mg/kg x 10), melphalan (70 mg/m2 x 2) and fludarabine (25mg/m2 x 5) followed by infusion of a CD34+ selected peripheral blood stem cell graft, without post alloHCT GVHD prophylaxis. Estimates were given using the Kaplan-Meier and cumulative incidence methods. Competing risks for relapse, NRM, and GVHD were death, relapse, and relapse or death respectively. The log-rank and Gray's test were used to assess univariable associations. GVHD by 6 months was assessed via a landmark analysis. Results Our 73 patient cohort had a median age of 55 (37-66) and was mostly male (74%). Most patients had low risk MM by ISS (50/66, 76%) and intermediate risk MM by R-ISS (45/66, 68%) at pre-salvage assessment. Patients had a median of 4 (2-9) pre-alloHCT lines of therapy and were evenly split between patients in PR and in VGPR or CR at time of alloHCT (50% and 49%). Median HCT-CI score was 2 (range 0-6) with the majority of patients graded as intermediate or high risk (score ≥1; 55/73, 75%). At a median follow-up in survivors of 35 months (12-84) OS and PFS rates were 70% and 53% at 1 year (95% CI 58-79, 41-64) and 50% and 30% at 3 years, respectively (38-62, 19-41). The cumulative incidences of relapse were 25% and 47% at 1 and 3 years, respectively (16-35, 35-58), and 1 year NRM was 22% (13-32). Deaths were balanced between relapse and non-relapse causes (54% and 46% respectively). Incidence of grade II-IV acute GVHD was 7% at 100 days (3-14), and of chronic GVHD was 8% at 1 year (3-16). In univariable analysis, intermediate-high risk ISS assessed prior pre-alloHCT salvage therapy was associated with lower OS (3 year 30 v 54%, p=0.037), lower PFS (3 year 9 v 33%, p=0.013), and greater relapse incidence (3 year 72 v 39%, p=0.004). Older age and GVHD prior to 6 months were also associated with lower OS; older age, more heavily pre-treated disease, and worse disease status at alloHCT were associated with lower PFS; and heavier pre-alloHCT treatment was also associated with higher relapse (Table 1). Higher HCTCI was not associated with increased NRM (1 year 22 v 16 v 27% for HCTCT 0, 1-2, ≥3 respectively; p = 0.863). Discussion We describe a cohort of high-risk heavily pretreated RRMM patients with durable OS (50% at 3 years), comparatively low PFS (30% at 3 years), and historically improved rates of NRM (22% at 1 year). We also importantly identified numerous pre-alloHCT variables that were associated with survival, PFS, and relapse. Amongst these, poor ISS measured prior to pre-alloHCT salvage was consistently associated with worse survival and relapse outcomes and may speak to this score's utility as a dynamic measure of disease risk in patients exposed to multiple lines and therapy. Conclusions Our report reinforces that CD34+ selected alloHCT can achieve prolonged disease control and long term survival in high risk, heavily treated refractory MM populations, and newly describes certain pre-transplant variables that may help identify patients with better potential survival and relapse outcomes. Given the dismal prognosis and lack of established alternate therapies for RRMM patients, we advocate that identification of favorable or adverse pre-transplant variables during pre-alloHCT assessment be used to inform alloHCT decision-making rather than to exclude certain patient cohorts from this potentially effective and curative treatment option. Disclosures Perales: Abbvie: Other: Personal fees; Merck: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Takeda: Other: Personal fees; Novartis: Other: Personal fees.

Novel Conditioning Regimen for Haploidentical Hematopoietic Cell Transplant for Severe Aplastic Anemia in Children

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5651-5651 ◽  
Author(s):  
Hasan Hashem ◽  
Rawad Rihani ◽  
Eman Khattab ◽  
Mayada Abu Shanap ◽  
Abdelghani Tbakhi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Peripheral Blood ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Stem Cell Source ◽  
Cell Source

New hematopoietic cell transplant (HCT) approaches are urgently needed for patients with severe aplastic anemia (SAA) who lack an HLA-identical donor. Haploidentical HCT with post transplant cyclophosphamide (PTCy) represent a potential universal available option for almost all children with SAA. We present a novel conditioning regimen for haploidentical HCT in children with SAA in a center where horse ATG is not available. Conditioning regimen consists of rabbit ATG 2.5 mg/kg/day from day -9 to -7, Fludarabine 30 mg/kg/day from day -6 to -2, Cyclophosphamide 14.5 mg/kg/day from day -6 to -5, Thiotepa 5 mg/kg/day from day -4 to -3, and 4 Gy TBI on day -1 in in two fractions. GvHD prophylaxis consist of PTCy 50 mg/kg/day on days +3 and +4 along with Cyclosporine A and Mycophenolate mofetil (MMF) starting on day +5. Four consecutive children with SAA referred to our center for haploidentical HCT starting in 2018. Median age at HCT was 9 years (5-16) with 3 males and 1 female. All patients were heavily transfused with both blood and platelets prior to referral for HCT. Two patients had strong and one had weak positive anti-HLA antibodies (DSAs) and received desensitization with IVIG, Rituximab and plasmapheresis. One patient received buffy coat infusion on day -1 due to persistent strong DSAs despite desensitization. Median CD34+ dose received was 12 x 10e6, and median CD3+ dose was 29 x 10e6. Donors were all same blood group to patients. All patients successfully engrafted neutrophils at median of 13 days (12-14). Platelets engraftment in 3/4 patients at median of 7 days (5-10). All patients received peripheral blood as stem cell source. Three of four patients survived and doing well at last follow up. One patient had toxic death on day +38 due to chemotherapy related toxicity causing multi-organ failure. Chimerism analysis was full donor in all four patients at median follow up time of 11 months (2-12). Patients were sent home at median of 24 days post HCT. None developed grade 2-4 acute GvHD nor chronic GvHD. Acute GvHD of skin grade 1 stage 1 developed in 2 patient and managed with topical steroids. Viral reactivations consisted of CMV viremia and BK hemorrhagic cystitis in all patients, and have all resolved. No post transplant autoimmune complications. Haploidentical HCT with PTCy represents a quick and first line approach in heavily transfused children with SAA. Although yet limited number of patients, this regimen is feasible and appears to be safe. A great advantage of this regimen is the rapid engraftment of both neutrophils and platelets. Moreover, although using peripheral blood as a stem cell source, there was no severe acute or chronic GvHD. Disclosures No relevant conflicts of interest to declare.

Antipneumococcal Seroprotection Years After Vaccination in Allogeneic Hematopoietic Cell Transplant Recipients

2019 ◽  
Vol 71 (8) ◽  
pp. e301-e307
Author(s):  
Christine Robin ◽  
Mathilde Bahuaud ◽  
Rabah Redjoul ◽  
Mohamed Jeljeli ◽  
Mathieu Leclerc ◽  
...  
Keyword(s):  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Igg Antibody ◽  
Seroprotection Rate ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Cord Blood Unit ◽  
Antibody Titers

Abstract Background International guidelines recommend vaccinating allogeneic hematopoietic cell transplant (HCT) recipients at 3 months after transplant, giving 3 doses of pneumococcal conjugate vaccine (PCV) followed by either a dose of 23-valent pneumococcal polysaccharide vaccine (PSV23) or a fourth PCV dose in the case of graft-versus-host disease (GvHD). However, the long-term immunity after this regimen is unknown, and there is no recommendation from 24 months after transplant regarding boosts. Our objective was to assess the antipneumococcal antibody titers and seroprotection rates of allogeneic HCT recipients years after different schedules of vaccination. Methods We assessed 100 adult HCT recipients a median of 9.3 years (range: 1.7–40) after transplant. All patients had received at least one dose of PCV and were assessed for antipneumococcal immunoglobulin G (IgG) antibody titers against the 7 serotypes shared by PCV7, PCV13, and PSV23. Sixty-six percent of the patients had been vaccinated according to the current guidelines. Results Considering an IgG titer ≥ 0.35 µg/mL as protective for each serotype, the seroprotection rate was 50% for 7/7 serotypes and 70% for 5/7 serotypes, with no differences between the different vaccination schedules. The lack of seroprotection was associated with a transplant performed not in complete remission or from a cord-blood unit, a relapse after transplant, or chronic GvHD at assessment. Conclusion Because only half of the vaccinated patients had long-term protection, pending prospective studies defining the best boost program after the initial one, we recommend the assessment of specific IgG titers starting from 24 months to decide for further doses.

scholarly journals Allogeneic Hematopoietic Cell Transplant for Systemic Juvenile Idiopathic Arthritis and Macrophage Activation Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Nicole Davidson ◽  
Hemalatha G. Rangarajan ◽  
Kyla Driest ◽  
Rajinder P. S. Bajwa ◽  
Veronika Polishchuk ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Macrophage Activation Syndrome ◽  
Macrophage Activation ◽  
Conditioning Regimen ◽  
Systemic Juvenile Idiopathic Arthritis ◽  
Hematopoietic Cell ◽  
Cell Transplant ◽  
Hematopoietic Cell Transplant ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Activation Syndrome

Systemic juvenile idiopathic arthritis (sJIA) is characterized by arthritis, fever, rash, lymphadenopathy, hepatosplenomegaly, and serositis. Macrophage activation syndrome is the most feared complication of sJIA with a high risk of mortality. We report a 16-year-old female diagnosed with refractory systemic juvenile idiopathic arthritis (sJIA) complicated by recurrent macrophage activation syndrome (MAS), severe joint disease, and lung involvement requiring prolonged immunosuppressive therapy. She received a matched unrelated allogeneic hematopoietic cell transplant (Allo-HCT) using a reduced-intensity conditioning regimen and is now, 3 years after the transplant, with complete resolution of sJIA symptoms, off immunosuppressants, and with significant improvement in the quality of life.

scholarly journals Fludarabine/Busulfan Plus Low Dose TBI As Reduced Intensity Conditioning in Older Patients Undergoing Allogeneic Hematopoietic Cell Transplant for Myeloid Malignancies

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4652-4652
Author(s):  
Manar Mohamed Ibrahim Khalil ◽  
Hans A. Messner ◽  
Jeffrey H. Lipton ◽  
Dennis Dong Hwan Kim ◽  
Auro Viswabandya ◽  
...  
Keyword(s):  
Low Dose ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Cell Transplant ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Cell Transplant ◽  
Myeloid Malignancies ◽  
Allogeneic Hematopoietic Cell Transplant ◽  
Time Period ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic cell transplant (HCT) is potentially curative for myeloid malignancy when indicated. In patients age 60 years or older HCT has become feasible with the use of reduced intensity conditioning (RIC) and studies have shown improved outcome in this older population. There is no clear consensus concerning the superiority of any single reduced intensity conditioning regimen for elderly patients with myeloid malignancies. At the Princess Margaret Cancer Centre we have been using a combination of fludarabine/busulfan plus low dose total body irradiation (TBI) as the sole RIC regimen since the year 2006. We present a retrospective analysis on the outcomes of 116 patients aged 60 to 71 years who underwent allogeneic HCT during the time period 2006-2015 for myeloid malignancies. A total of 40 patients (34%) underwent RIC HCT during the years 2006-2010 and 76 patients (66%) during the years 2011-2015. Median age at HCT was 64 years (range 60-71). AML was diagnosed in 73 patients (63%) while 43 had other myeloid malignancies (MDS=34, CMML=8, blastic plasmacytoid dendritic cell neoplasm=1). Seventy four patients (64%) had de novo and 42 (36%) had secondary disease. Cytogenetics were available for 108 patients (93%), 17 favorable (16%), 59 intermediate (54%) and 32 unfavorable risk (30%) (MRC criteria for AML and IPSS for MDS/CMML). All leukemia patients were in first remission (<5% blasts) and MDS/CMML patients had less than 10% marrow blasts at HCT. As for pre-transplant comorbidity risk, 59 patients (51%) had HCT-CI score of 0-2 and 57 (49%) had a score of 3 or more. Donors were HLA matched related in 63 patients (54%), all other donors were unrelated including 19 mismatched (16%). Both recipient and donor were cytomegalovirus sero-negative in 28 (24%) cases. Female donor to male recipient occurred in 27 (23%) cases. Grafts were peripheral blood stem cells (PBSC) in almost all the patients (n=114, 98%). All patients (n=116) received RIC conditioning with fludarabine 30mg/m2/day for 4 days (day -5 to day -2), busulfan 3.2mg/kg (adjusted BW)/day for 2 days (day -3 to day -2 and TBI 200 cGy x one dose (on day -1). Median follow-up of survivors was 39 months (range 6.5 -121). Median neutrophil engraftment (≥0.5 x10e9/L) was 18 days (range 12-35 days), median platelet engraftment (≥20 x10e9/L) was 11 days (range 7-49 days). Two patients never engrafted and 23 patients did not have a decrease in platelets <20 x10e9/L at any time. Acute graft versus host disease (GVHD) grade II-IV occurred in 59 patients (51%) while grade III-IV was seen in 34 patients (29%). Chronic GVHD at any time was seen in 52 patients (45%). Relapse occurred in 27 patients (23%). Of the 81 patients that died, the primary cause of death was GVHD in 25 patients (31%), disease relapse in 25 patients (31%), infection in 18 patients (22%), and graft failure in 6 patients (7%). Data was not available in 3 patients (4%) and 4 patients (5%) died from other causes. Overall survival (OS) for the entire cohort at 3 years was 33% (95% CI 24-42) on univariate analysis. Type of myeloid malignancy (AML versus others, p=0.007), donor type (p= 0.001), HLA mismatch (p= 0.06) and transplant time period (p= 0.05) were the only variables which showed p<0.1 on univariate analysis for OS. Cumulative incidence of relapse (CIR) at 3 years was 24% (95% CI 16-32). Non-relapse mortality (NRM) at 3 years was 43% (95% CI 34-52). Multivariable analysis for OS using the variables with p<0.1 demonstrated AML patients to have a superior outcome compared to other myeloid malignancies (HR 0.62, 95% CI 0.39-0.99, p=0.045), as well as patients with related donors (HR 0.52, 95% CI 0.33-0.82, p=0.005). For CIR none of the variables were found to be significant. For NRM, AML patients had superior outcome (HR 0.57, 95% CI 0.33-0.97, p=0.038), as well as patients with related donors (HR 0.55, 95% CI 0.33-0.94, p=0.028). Based on the above findings, OS was determined for the AML patients that underwent related donor transplant with this regimen (n=45). Three year OS was 51% (95% CI 36-65) for the AML patients who underwent related donor transplant versus 21% (95% CI 12-32) for the group which included AML with unrelated donors and those with other myeloid malignancies (p= 0.0003) (see figure). We conclude that fludarabine/busulfan plus low dose TBI is an effective conditioning regimen for older patients with myeloid malignancies, in particular for AML patients in first remission with matched related donors. Figure Figure. Disclosures No relevant conflicts of interest to declare.

High response rate in refractory and poor-risk multiple myeloma after allotransplantation using a nonmyeloablative conditioning regimen and donor lymphocyte infusions

Blood ◽  
2001 ◽  
Vol 97 (9) ◽  
pp. 2574-2579 ◽  
Author(s):  
Ashraf Badros ◽  
Bart Barlogie ◽  
Christopher Morris ◽  
Raman Desikan ◽  
Sara R. Martin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Residual Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Response Rate ◽  
Cell Transplant ◽  
Poor Risk ◽  
Heavily Pretreated ◽  
Donor Lymphocyte Infusions

Abstract Standard allogeneic stem cell transplant (allo-SCT) regimens have been associated with a high transplant-related mortality (TRM) in multiple myeloma (MM). Nonmyeloablative therapy can establish stable engraftment after allo-SCT and maintain the antitumor effect with less toxicity, which is important in heavily pretreated and elderly patients. We report on 16 poor-risk MM patients receiving allo-SCT from an HLA-matched (n = 14) or mismatched (n = 2) sibling following conditioning with melphalan 100 mg/m2 (MEL-100). Ten patients had refractory relapse, 4 responsive relapse, and 2 patients were in near complete remission (nCR) with poor-prognosis disease. Patients had received 1 (n = 9) or 2 (n = 7) prior autotransplants. Donor lymphocyte infusions (DLIs) were given to 14 patients with no clinical evidence of graft versus host disease (GVHD) either to attain full donor chimerism (n = 4) or to eradicate residual disease (n = 10). Fifteen patients showed myeloid engraftment, and 12 patients were full donor chimeras at day +21. No TRM was observed during the first 100 days. Acute GVHD developed in 10 patients; 1 had fatal grade IV GVHD. Seven progressed to chronic GVHD, limited in 3 and extensive in 4 patients. At a median follow-up of 1 year, 5 patients achieved and sustained CR, 3 nCR, and 4 partial remission. Of 4 patients progressing after transplantation, 3 achieved a remission following further chemotherapy and DLI. Remarkable graft versus myeloma responses were seen in chemotherapy-refractory patients. Two patients died of progressive disease, and 3 died of GVHD complications without active disease. GVHD remains a major problem with this procedure.

Transplant Outcomes in High-Risk (Class 3) Patients with Thalassemia Treated with a Modified Protocol Are Equivalent to Low/Intermediate-Risk (Class 1/Class 2) Patients

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 620-620 ◽  
Author(s):  
Javid Gaziev ◽  
Gioia De Angelis ◽  
Antonella Isgro ◽  
Pietro Sodani ◽  
Marco Marziali ◽  
...  
Keyword(s):  
Iron Overload ◽  
Total Dose ◽  
Graft Failure ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Free Survival ◽  
Risk Class ◽  
Transfusion Independence ◽  
Class 1

Abstract Introduction. Bone marrow transplantation (BMT) for class 3 patients with thalassemia is challenging due to high rates of graft rejection and transplant-related mortality. Since the first studies of BMT in the late 1980s, a number of conditioning regimens have been designed to improve outcomes, but with suboptimal results. Here we report the outcome of transplantation in class 3 patients using a modified protocol. Methods. Between July 2004 and May 2015, 68 consecutive patients of 5-16.6 years of age with class 3 thalassemia received their first BMT from HLA-identical sibling donors. Of these patients, 26 were prepared for transplantation with the original protocol (Protocol 26) and 42 patients (since February 2007) with the modified protocol. The original protocol started with a preconditioning phase during which patients received hydroxyurea (30 mg/kg/day) and azathioprine (3 mg/kg/day) from day −45 pre-transplant, and fludarabine (20 mg/m2/day) from day −16 through day −12. Conditioning regimen included oral or intravenous (i.v.) busulfan and cyclophosphamide 160 mg/kg total dose. The modified protocol started with the same preconditioning phase except with 30 mg/m2/day of fludarabine. The conditioning regimen comprised i.v. Bu, thiotepa 10 mg/kg/day, and cyclophosphamide 160 mg/kg total dose. We compared the outcomes between these two groups.The two groups showed similar patient demographics. Patients in both groups had moderately severe iron overload, as evidenced by high median serum ferritin and liver iron concentrations. The median liver fibrosis score in the original and modified protocol-treated patients was 2 (range, 1-4) and 1 (range 1-5) (p=0.22), respectively. Results. At day 0, the degree of cytoreduction (lymphopenia, neuthropenia and thrombocytopenia) achieved by the modified protocol was significantly higher than the original protocol. Overall, 22 (84.6%) original protocol-treated patients and all 42 modified protocol-treated patients showed sustained engraftment. Platelet and neutrophil engraftment kinetics were similar between groups. All patients with sustained engraftment achieved RBC transfusion independence, with a median time to transfusion independence of 19 days (range, 0-88) with original protocol and 20 days (range, 0-85) with modified protocol. Among original protocol-treated patients, two experienced primary graft failure and two experienced secondary graft failure. No modified protocol-treated patients exhibited graft failure. Competing-risk analysis showed a significantly higher cumulative incidence of graft failure with original protocol (15%) compared to modified protocol (0%) (p=0.010). At the time of survival analysis, 22 original protocol -treated patients (85%) and 39 modified protocol-treated patients (93%) were alive, with median follow-up durations of 8.8 years (range, 8.2-10.8 years) and 3.5 years (range, 0.4-8 years), respectively. The 5-year probabilities of thalassemia-free survival were 93% with modified protocol and 73% with original protocol (p=0.032). The respective probabilities of overall survival were 93% and 85% (p=0.37). The incidence of grade 2-4 acute GVHD was 46% in the original and 24% in the modified group (p=0.066). Respective incidences of chronic GVHD were 12% and 5%. At present all patients are off immunosuppressive medication. There were 4 deaths in the original group and 3 deaths in the modified group. The most frequently observed toxicities were grade 2 elevations in AST and ALT, followed by grade 2 oral mucositis and diarrhea with similar rates in both groups. Few patients experienced grade 3 liver and gut toxicities in either groups with similar rates. There was no difference in the rate of infectious complications between the two groups. One patient in each group developed moderate hepatic VOD, both of which resolved with supportive care Conclusions. Modified treatment protocol effectively and safely prevented graft failure/rejection and significantly improved thalassemia-free survival of class 3 patients. Importantly, the treatment intensification was not associated with increased nonhematological toxicity, even though these patients suffer from pre-existing organ damage due to iron overload and/or hepatitis. Modified protocol makes allogeneic BMT accessible to all class 3 younger patients with results equal to class 1 or class 2 patients with thalassemia. Disclosures No relevant conflicts of interest to declare.

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