Myeloablative Treosulfan as Preparative Regimen for Allogeneic Haematopoietic Stem Cell Transplantation: A Single-Centre Experience.

Abstract Treosulfan (TREO), a water-soluble bifunctional alkylating agent, has demonstrated strong immunosuppressive and antileukemic activity as well as profound stem cell toxicity in animal studies. Due to the advantageous clinical toxicity profile lacking significant non-hematologic organ toxicities, high-dose TREO in combination with cyclophosphamide (CY) has recently been evaluated in patients (pts) with an increased risk for organ toxicities precluding standard myeloablative conditioning regimens before allogeneic stem cell transplantation (SCT). Between 8/00 and 10/03, we treated 52 patients (pts) not eligible for conventional therapy with TREO in order to reduce toxicity in a myeloablative setting. Diagnoses were AML (n=14), ALL (n=11), MM (n=8), NHL (n=7), MDS (n=5), CML (n=4) and aplastic syndromes (n=3). 18 patients were grafted in early disease (1st or 2nd complete remission, chronic phase, or incipient first relapse (BM blasts < 10%). The remaining pts were classified as having advanced disease. Donors were identical siblings (n=24), non-identical family members (n=l), matched unrelated (n=14) or mismatched unrelated (n=13) donors. Conditioning regimen consisted of TREO 36g/qm (n=19) or 42g/qm (n=28) and CY 120mg/kg BW, 5 pts received TREO 42g/qm and fludarabine 150mg/qm. GvHD prophylaxis consisted of CSA alone (n=l) or in combination with short course MTX (n=25), alemtuzumab (n=22) or ATG (n=4). ANC > 500/μl and platelets > 20000/μl were reached at day 15 and 16 respectively. Acute GvHD grade II - IV occurred in 31% of pts and chronic GvHD in 60% of pts. Overall (OS) and disease free survival (DFS) were closely related to disease status. OS and DFS was 93% and 82,9% after a median of 18 months (range 0,9–38,5 months) for pts with early disease. In advanced disease the OS was 57,4% and the DFS 47,9% after a median of 4,8 months (range 0,3 – 22,9 months), respectively. In early disease, a single patient died of invasive aspergillosis associated with grade IV aGvHD. Another patient developed a relapse of CML which was successfully treated with DLI. Clinical relevant adverse events occurred in patients with advanced disease: MOF (n=7), VOD (n=2), infectious problems associated to GvHD grades II – IV (n=4), and pulmonary embolism (n=l). TREO as part of a myeloablative regimen seems to be effective and safe even in pts not eligible for conventional myeloablative therapy.

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Phase II Multicenter Trial To Evaluate the Safety and Efficacy of Low-Toxicity Treosulfan/Fludarabine Conditioning Prior to Allogeneic Haematopoietic Stem Cell Transplantation in Patients with Acute Myeloid Leukemia.

Blood ◽

10.1182/blood.v110.11.621.621 ◽

2007 ◽

Vol 110 (11) ◽

pp. 621-621 ◽

Cited By ~ 1

Author(s):

Jerzy Holowiecki ◽

S. Giebel ◽

D. Beelen ◽

R. Trenschel ◽

H. Wandt ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Phase Ii ◽

Cumulative Incidence ◽

Haematopoietic Stem Cell ◽

High Dose ◽

Hematopoietic Stem ◽

Safety And Efficacy ◽

Increased Risk

Abstract BACKGROUND: The toxicity of commonly used myeloablative regimens is the main factor limiting applicability and restricting upper age limit for allogeneic hematopoietic stem cell transplantation (alloHSCT). However, reduced intensity conditioning (RIC) protocols are associated with high risk of relapse. Previous dose-escalation trials revealed high-dose treosulfan-based conditioning an alternative treatment with myeloablative as well as antileukemic potential, accompanied by low non-hematological toxicity. The goal of this multicenter phase II trial was to evaluate safety and efficacy of treosulfan/fludarabine conditioning in AML patients. PATIENTS AND METHODS: Seventy-five patients (median age 45 years, range 19–59) with AML in 1st (80%), 2nd (17%), or 3rd (3%) complete remission were treated with alloHSCT from either matched related (MRD, 40%) or unrelated donors (MUD, 60%). Preparative regimen consisted of treosulfan 14 g/m2/day on days −6 to −4, fludarabine 30 mg/m2/day on days −6 to −2, and in case of MUD-HSCT additionally ATG (Fresenius) 10 mg/kg/day on days −4 to −2. Graft-vs.-host disease (GvHD) prophylaxis consisted of cyclosporine and short-course methotrexate. 25% of the patients had an increased risk of toxicity for standard myeloablative conditioning regimens because of higher age or co-morbidities. RESULTS: All patients engrafted after a period of absolute neutropenia with the median time to ANC >0.5 G/L and PLT >50 G/L of 21 (13–39) days and 19 (11–48) days, respectively. The cumulative incidence of complete donor chimerism was 72% on day +28 and 92% on day +100. Most frequent CTC grade 3 or 4 complications until day 28 after transplantation were febrile neutropenia (28%), infection in neutropenia (16%), and mucositis (5%). None of the patients experienced severe hepatic toxicity, including VOD. After a median follow up of 457 days (98–988), the probabilities of overall (OS) and disease-free survival (DFS) at 2 years equaled 67% resp. 58% (MRD-HSCT) and 58% resp. 45% (MUD-HSCT, p=NS). The 2-year cumulative incidence of relapse was 34% for MRD-HSCT and 37% for MUD-HSCT, whereas non-relapse mortality was 8% and 17%, respectively. Outcome was not significantly influenced by disease status (CR1 vs. ≥CR2) or age. CONCLUSIONS: Conditioning therapy based on treosulfan at a dose of 3x14 g/m2 in combination with fludarabine is very well tolerated, resulting in a low NRM. The regimen demonstrated reliable efficacy in AML patients with confirmed first or subsequent remission. Further randomized studies are warranted to verify advantageous survival results.

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Corrigendum to treating relapsed and refractory metastatic germ cell tumours with high-dose chemotherapy with carboplatin and etoposide and autologous haematopoietic stem cell transplantation

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155221990224 ◽

2021 ◽

Vol 27 (2) ◽

pp. NP1-NP1

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Germ Cell ◽

Cell Transplantation ◽

Haematopoietic Stem Cell Transplantation ◽

High Dose Chemotherapy ◽

Haematopoietic Stem Cell ◽

High Dose ◽

Germ Cell Tumours

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Haematopoietic stem cell transplantation

10.1093/med/9780199683307.003.0009 ◽

2015 ◽

Author(s):

Drew Provan ◽

Trevor Baglin ◽

Inderjeet Dokal ◽

Johannes de Vos ◽

Hassan Al-Sader

Keyword(s):

Stem Cells ◽

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Fungal Infections ◽

Chronic Gvhd ◽

Haematopoietic Stem Cell ◽

Sinusoidal Obstruction Syndrome ◽

Cell Transplant ◽

Post Transplant

Haemopoietic stem cell transplantation (SCT) - Indications for haemopoietic SCT - Allogeneic SCT - Autologous STC - Investigations for BMT/PBSCT - Pretransplant investigation of donors - Bone marrow harvesting - Peripheral blood stem cell mobilization and harvesting - Microbiological screening for stem cell cryopreservation - Stem cell transplant conditioning regimens - Infusion of cryopreserved stem cells - Infusion of fresh non-cryopreserved stem cells - Blood product support for SCT - Graft-versus-host disease (GvHD) prophylaxis - Acute GvHD - Chronic GvHD - Veno-occlusive disease (syn. sinusoidal obstruction syndrome) - Invasive fungal infections and antifungal therapy - CMV prophylaxis and treatment - Post-transplant vaccination programme and foreign travel - Longer term effect post-transplant - Treatment of relapse post-allogeneic SCT - Discharge and follow-up

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Prior Rituximab Reduces Relapse and Improves Survival Following High Dose Chemotherapy and Stem Cell Transplantation for Relapsed Composite Low and Intermediate Grade (Including Transformed) Lymphoma.

Blood ◽

10.1182/blood.v108.11.3662.3662 ◽

2006 ◽

Vol 108 (11) ◽

pp. 3662-3662

Author(s):

Khaled M. Ramadan ◽

Joseph M. Connors ◽

Abdulwahab J. Al-Tourah ◽

Randy D. Gascoyne ◽

Kevin Song ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Residual Disease ◽

Chronic Gvhd ◽

High Dose Chemotherapy ◽

Clinicopathological Characteristics ◽

High Dose ◽

Intermediate Grade ◽

Non Hodgkin Lymphoma

Abstract The effect of prior exposure to rituximab (ritux) on relapse (REL) and survival following stem cell transplantation (SCT) in patients (pts) with REL composite low and intermediate grade non-Hodgkin lymphoma (L/I-NHL) is unknown. Fifty-four pts with REL L/I-NHL underwent high-dose chemotherapy (CT) and SCT Jan ’89 to June ’05. Follow-up is complete to April ’6 with a median of 32 mo. Ritux was added to CT regimens since 2001 and given at 375 mg/m2. Eighteen pts received ritux at initial diagnosis of NHL or after REL with salvage CT prior to SCT. Pts proceeded to high dose CT with allogeneic (allo) (n=12) or autologous (auto) SCT (n=6). This group was compared with a group of pts not receiving ritux pre-SCT (n=36)(Table 1). Eleven pts (61%) are alive in the ritux group compared with 11 pts (31%) in the non-ritux group. The 2 and 4-y OS for pts who received ritux were 52% and 52%, vs 36% and 24% (p=.12, RR=.52) for pts who did not receive ritux. The EFS were significantly different with 2 and 4-y EFS for the ritux group 56% and 56% vs 24% and 18% (P=.038, RR=.42) for the non-ritux group (figure 1). No effect was seen on TRM. The risk of REL post SCT was significantly lower in the ritux group (p=.017)(figure 2). Two of 18 pts (11%) had NHL REL in the ritux vs 18 of 36 (50%) in the non-ritux group. The hazard rate of REL in pts who received ritux was 20% that of pts in the non-ritux group. Significance maintained in multivariate analysis (p=.016). No impact was seen on graft-versus-host disease (GVHD). Fifty percent and 61% of pts developed acute GVHD grades 2–4 and 50% and 64% of pts developed chronic GVHD in the ritux and non-ritux groups respectively. In conclusion, prior treatment with ritux in pts with relapsed composite L/I-NHL undergoing SCT was associated with reduced risk of REL and improved survival without associated increase in toxicity. Further analysis is underway to clarify the nature of this important finding. Table 1: Clinicopathological characteristics of ritux and non-ritux groups Parameter$ Rituximab group, n=18 (%) Non-rituximab group, n=36 (%) $ all p values are >0.1. *at diagnosis Median age at SCT 48 y 44 y M:F 2.6:1 1.6:1 Allo-SCT 12(67) 28(78) BM involvement* 10(56) 22(61) B symptoms* 7(39) 10(28) Prior purine analogue therapy 8(44) 11(31) Residual disease prior to SCT 9(50) 14(39) TBI in conditioning 13(72) 30(83) Figure Figure Figure Figure

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Allogeneic Stem Cell Transplantation for Relapsed Follicular Non-Hodgkin’s Lymphoma: Single Centre Experience.

Blood ◽

10.1182/blood.v110.11.5054.5054 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5054-5054

Author(s):

Amir Peyman ◽

Stephen Couban ◽

Kara Thompson ◽

Louis Fernandez ◽

Donna L. Forrest ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Follicular Lymphoma ◽

Cell Transplantation ◽

Chronic Gvhd ◽

Disease Free Survival ◽

High Dose ◽

Hematopoietic Stem ◽

Free Survival ◽

Grade 3

Abstract Between 1993 and 2005, 57 patients with follicular lymphoma underwent high-dose chemo/radiotherapy and allogeneic hematopoietic stem cell transplantation (HSCT), 49 Allogeneic, (16 Bone Marrow and 33 Peripheral Blood), 6 MIN, 2 MUD. Median age was 47 years. Median days to neutrophil and platelet engraftment after HSCT were 18 and 13 days respectively. Twenty-five patients experienced Acute GVHD and thirty-four had Chronic GVHD (12 mild and 22 extensive). Thirty-three patients were in grade 1, 17 in grade 2, 4 in grade 3 and 3 grade 4. As of their FLIPI score, 4, 14, 21 and 18 patients were calculated to have score of 0, 1, 2 and 3 respectively. Forty-one patients are alive. Two patients have relapsed, one a year and the other two years after HSCT. The 5 year survival was 71.9% (95% CI 57.5–82.2%) and 5 year survival was 67.2% (95% CI 52.3–78.5%). Transplant related mortality rate (TRM) in 5 year was 22.4% (95% CI 63.6–86.8%). No significant differences was found among FLIPI groups 0,1,2 and 3 in terms of overall, relapse-free survival, TRM Allogeneic HSCT for patients with progressive follicular lymphoma is feasible and may result in prolonged disease-free survival.

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Fludarabine, Amsacrine, High-Dose Cytarabine and Total Body Irridation Followed by Allogeneic Stem Cell Transplantation for the Treatment of High Risk or Relapsed Acute Lymphoblastic Leukemia.

Blood ◽

10.1182/blood.v110.11.5086.5086 ◽

2007 ◽

Vol 110 (11) ◽

pp. 5086-5086

Author(s):

Fabian Zohren ◽

Thorsten Graef ◽

Ingmar Bruns ◽

Akos Czibere ◽

Fenk Roland ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Chronic Gvhd ◽

Good Condition ◽

White Blood Count ◽

High Dose ◽

Unrelated Donor ◽

Grade Iii

Abstract In this prospective study we examined the use of an intensified conditioning regimen followed by allogeneic blood-stem-cell transplantation (BSCT) for the treatment of young adults in physically good condition with relapsed or high risk acute lymphoblastic leukaemia (ALL). Eleven patients with ALL received FLAMSA chemotherapy (fludarabine 30mg/m2 - cytarabine 2000mg/m2 -amsacrine 100 mg/m2 on day −10, − 9, − 8and −7), Anti-Thymocyte-Globulin (ATG 20 mg/kg BW on day −6, −5 and −4) and fractionated TBI (2 x 2 Gy on day −3, − 2 and −1) followed by matched unrelated donor (n=10) or matched sibling donor (n=1) SCT. The principle reasons for high risk stratification were refractory disease during first-line induction therapy (6, 55%), relapse (2, 18%), extramedullary disease manifestation (1, 9%), ALL subtype (6, 55%), unfavorable cytogenetics (5, 45%) and white blood count >30000 μL at time of diagnosis (3, 27%). After a median follow-up time of 604 days (range 202 – 1042 days) 8 patients (73%) are alive and 3 patients (27%) died. The median overall survival was not reached. Two patients died after relapse on days +121 and +449, another patient died from treatment related complications (HUS-TTP) on day +87. One patient relapsed on day +200 and is currently alive, the remaining 7 patients are alive and free of desease. Treatment related toxicities were acceptable. With 6 out of 11 patients developing grade III/IV infections during neutropenia, infectious complications remained of major importance. Other non-haematological side effects seen within this group of patients were less frequent and almost exclusively limited to gastrointestinal toxicities. Five patients (45%) had grade III/IV mucositis and 5 patients (45%) had grade III/IV nausea, while 4 patients (36%) showed grade III/IV diarrhoea. There was no case of acute toxicity related to the cardiavascular or central nervous system. The incidence of acute GvHD (aGvHD) was 36% (n = 4) and limited to grades II-III. Eight patients were evaluable for chronic GvHD (cGvHD). Out of those 4 patients (36%) developed cGvHD (3 limited disease, 1 extensive disease). We conclude that allogeneic transplatation after the FLAMSA-ATG-TBI regimen is feasible and provides effective therapy for this group of high-risk patients.

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Evaluation of NIH Consensus Criteria for Classification of Late Acute and Chronic Gvhd in Reduce Intensity Conditioning (RIC) Stem Cell Transplantation (SCT).

Blood ◽

10.1182/blood.v114.22.1139.1139 ◽

2009 ◽

Vol 114 (22) ◽

pp. 1139-1139 ◽

Cited By ~ 1

Author(s):

Jifang Zhou ◽

Sylvain Thepot ◽

Aurrore Perrot ◽

Marie Robin ◽

Regis Peffault de Latour ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Cumulative Incidence ◽

Acute Gvhd ◽

Late Onset ◽

Chronic Gvhd ◽

Time Dependent ◽

Increased Risk ◽

Nih Consensus Criteria

Abstract Abstract 1139 Poster Board I-161 Background Chronic graft-versus-host disease (GVHD) occurs frequently after allogeneic stem cell transplantation (SCT) and has an impact on morbidity and survival. The National Institutes of Heath (NIH) consensus criteria for the diagnosis of GVHD, emphasized clinical manifestations of GVHD rather than the classical time of onset (day 100). Incidence and impact in term of relapse and no-relapse mortality (NRM) of this new classification is not well known after RIC. Methods We retrospectively reviewed 116 consecutive patients (pts) in Saint Louis' Hospital undergoing an SCT for hematologic malignancy and surviving at least day + 100 after RIC between August 2005 and December 2008. We evaluated non-relapse mortality (NRM) and recurrent malignancy. Cumulative incidence was computed using death as a competing event. Incidence of relapse and NRM was counted from 100 days post-transplant for patients without chronic GVHD or from chronic GVHD onset. Patients with relapse/progression before chronic GVHD onset were considered as not having chronic GVHD in these analyses. The association of occurrence of chronic GVHD with the risk of relapse and non-relapse death was analyzed using time-dependent covariates in cause-specific proportional hazards models. Results Among 116 pts ( M/F: 71/45), with a median age of 53 years old (19-68 years) 28 pts (24%) were transplanted for acute leukemia in, 11 pts (9%) for chronic leukemia, 27 pts (23%) for lymphoma, 30 pts (26%) for MPD/MDS and 20 pts (17%) for plasma cell disorder. Sixty-three pts (54%) received HLA-identical sibling transplantation, 53 pts (46%) received transplantation from unrelated donors. Source of stem cells was mobilized peripheral blood stem cell for 108 pts (93%), bone marrow for 4 pts (3%) and 4 cord blood (3%). After a median follow-up of 18 months (range 5-45 months), a total of 67 pts (58%) developed chronic GVHD according to the Seattle day 100 landmark criteria and when using NIH consensus criteria, 55 pts (47%) developed chronic GVHD, including 43 pts (53%) with classic chronic GVHD and 8 pts (10%) overlap syndrome. Patients reclassified included; 3 pts with late onset acute GvHD, 19 pts had recurrent and 8 had persistent acute GVHD (numbers do not to previous sentence because some of these patients latter developed chronic GvHD). The cumulative incidence of chronic GVHD at 36 months was 64% (95%CI; 53%-73%) when using Seattle criteria compared to 56% (95%CI; 45%-67%) with NIH chronic GVHD criteria. Two-year Cumulative incidences of relapse and NRM using both classifications are summarized in Table. In Cox model with GvHD as a time dependent covariate, the NRM was significantly higher in patients with late onset, persistent and recurrent acute GVHD compared to no GVHD (hazard ratio (HR) 31, 47 and 30; p = 0.005, p <0.0001, p <0.0001, respectively), whereas the NRM was statistically increased in case of chronic GVHD using Seattle day 100 criteria (HR: 2.8; P=0.034). Conclusion The cumulative incidence of chronic GVHD “decrease” about 10% when using NIH consensus criteria compared to Seattle criteria in our cohort of RIC. Most of the NRM occurred beyond 100 days after SCT was due to the increased risk of NRM in patients with late onset, recurrent or persistent acute GVHD. Disclosures No relevant conflicts of interest to declare.

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No Direct Effect of NOD2/CARD15 Variants On Clinical Outcome After Non-Myeloablative Allogeneic Stem Cell Transplantation.

Blood ◽

10.1182/blood.v114.22.4322.4322 ◽

2009 ◽

Vol 114 (22) ◽

pp. 4322-4322

Author(s):

Hanneke M. van der Straaten ◽

Martine M. Paquay ◽

Marcel G.J. Tilanus ◽

Leo F. Verdonck ◽

Cynthia Huisman

Keyword(s):

Stem Cell ◽

Clinical Outcome ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Chronic Gvhd ◽

Conditioning Regimen ◽

Haematopoietic Stem Cell ◽

Significant Prognostic Factor ◽

Wild Type

Abstract Abstract 4322 Background Single nucleotide polymorphisms (SNPs) in the innate immunity receptor NOD2/CARD15 have been demonstrated to modulate the outcome of allogeneic haematopoietic stem cell transplantation. The effect of the NOD2/CARD15 polymorphism seems to be associated with donor source as well as type of conditioning regimen. Methods We reviewed NOD2/CARD15 mutations in all donor/recipient pairs of 192 consecutive patients who received non-myeloablative allogeneic stem cell transplantation(SCT) at our institution between 2002 and 2006. All patients were treated uniformly with fludarabine 30 mg/m2/day for 3 days followed by 200 cGy TBI (n=154) or TBI alone (n=38) and received grafts from HLA-matched related (n=132) or unrelated (n=60) donors. Results Mutated alleles were observed in 36 of 192 (19%) patients and in 35 of 192 (18%) donors. These SNPs, however, did not have a significant impact on clinical outcome data (P > 0.05, Kaplan Meier and Fine & Gray's test). Acute graft-versus-host disease (GVHD) occurred in 24 of 61 (39%) patients with the polymorphism and in 66 of 131 (50%) patients without the polymorphism. Chronic GVHD developed in 28 of 55 (51%) patients with SNP pairs and in 79 of 121 (65%) patients with the wild type. The incidence of transplant-related mortality was 21% in both groups, 13 of 61 patients in the group with the polymorphism and 27 of 131 without the polymorphism. Relapse was seen in 23 of 61 (38%) patients with the SNP pairs and in 48 of 131 (37%) wild type patients. Finally, overall survival was 43% (26/61) in patients with the polymorphism and 39% (51/131) in patients without the polymorphism. Conclusion These data indicate that mutations in the NOD2/CARD15 genes do not influence the clinical outcome of non-myeloablative allogeneic SCT directly. Since NOD2/CARD15 variants are not recognized as a single significant prognostic factor, screening for NOD2/CARD15 when selecting a donor does not seem to have additional value in patients undergoing non-myeloablative SCT. Disclosures: No relevant conflicts of interest to declare.

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High-Dose Rituximab in the Conditioning Regimen Before Allogeneic Stem Cell Transplantation Reduces the Incidence of Acute Gvhd in B-Cell Lymphomas

Blood ◽

10.1182/blood.v118.21.4546.4546 ◽

2011 ◽

Vol 118 (21) ◽

pp. 4546-4546

Author(s):

Paolo Corradini ◽

Barbara Sarina ◽

Cristiana Carniti ◽

Francesca Patriarca ◽

Angelo Michele Carella ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplantation ◽

B Cell ◽

Cell Transplantation ◽

Allogeneic Stem Cell Transplantation ◽

Immune Reconstitution ◽

Acute Gvhd ◽

Chronic Gvhd ◽

High Dose ◽

Unrelated Donors

Abstract Abstract 4546 Background: Reduced-intensity conditioning (RIC) followed by allogeneic stem cell transplantation (alloSCT) is an effective salvage therapy for relapsed lymphomas. The present GITMO study is a prospective multicenter phase II trial for patients affected by relapsed CD20 positive lymphomas. Compared with the previous thiotepa/fludarabine/cyclophosphamide GITMO protocol (Leukemia 2007), the thiotepa dose is increased, and high-dose Rituximab is included in the regimen to improve the outcome and possibly modulate the incidence of acute GVHD. Aims: Primary end-point was 1-year progression-free survival; secondary endpoints were non-relapse mortality and incidence of acute and chronic GVHD. Methods: Fifty-seven patients (pts) were enrolled so far in the study and 49 are evaluable for analysis. Treatment plan consisted of high-dose R (500 mg/ms on day -6) followed by thiotepa (12 mg/kg), fludarabine (60 mg/kg) and cyclophosphamide (60 mg/kg). Graft-versus-host disease (GVHD) prophylaxis included cyclosporine and mini-methotrexate; ATG (7.5 mk/kg) was only added for pts allografted from one antigen mismatched sibling or unrelated donors. Histopathological subtypes included 24 aggressive (HG) (n= 17 diffuse large B-cell lymphomas, n= 7 mantle cell lymphomas) and 25 indolent lymphomas (LG) (n= 13 follicular lymphomas, n= 12 small lymphocytic/chronic lymphocytic leukemia). Patients were allografted from related siblings (SIB) (n= 32 matched, n=1 one single mismatched) or unrelated donors (UD) (n=11 matched, n=5 mismatched). All the pts had chemosensitive disease (n=20, 41% in complete remission) and 26 (53%) came from a failed autoSCT. Results: At a median follow-up of 13 months (range, 5–44 months), 36 pts are alive [n=27 (75%) in CR] and 13 died from any cause [n=6 for non-relapse mortality (NRM), n=7 for disease progression]. All the patients engrafted (94% had full donor chimerism at 3 months). The cumulative incidence (CI) of NRM was 13% at 1 year: 9% vs 19% for SIB and MUD (p=0.3), and 9% versus 16% for for LG and HG (p=0.3), respectively. In total only 11 of 49 pts had acute GVHD (n=8 grade II, n=3 grade III) with an estimated CI of 21% at 100 days. In the previous GITMO study the incidence was 35% with SIB only. Forty pts are evaluable for chronic GVHD with an estimated CI of 41% and 47% at 1 and 2 year, respectively (n=11 limited, n=3 extensive). Infections after engraftment requiring hospitalization or intravenous treatment were evaluable in 46 pts (n=3 excluded for early death). The overall incidence of infections was 58% (n=27) including 5 pts experienced sepsis and 10 pts pneumonia. Preliminary data on immune-reconstitution at 1 year showed: 1) low number of circulating B cells (median CD19+/ul: 129/ul) with an expansion of naive cells (IgD+, CD27-); 2) the median value of IgM was 89 mg/dl whereas IgG and IgA remained at low levels. The CI of relapse was 26% and 37% at 1 year and 2 years, respectively. In the indolent and aggressive groups, OS estimates at 2 years were 79% (95%CI, 52%-91%) and 61% (95 CI, 38%-77%) and PFS estimates were 53% (95%CI, 23%-76%) and 48% (95% CI, 27%-66%), respectively. Conclusions: The present data suggest that the administration of high-dose R is feasible and causes an unexpected reduction of the incidence of acute GVHD without increasing the NRM and the incidence of severe infections complications. Complete data evaluating the effects of R on immune reconstitution are ongoing. Disclosures: No relevant conflicts of interest to declare.

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