Dual Cord Blood Unit (dCBU) Transplantation Increases Short-Term Morbidity, but Has Similar Long-Term Outcome Compared to Matched Unrelated Donor (MUD) Transplantation After Myeloablative Conditioning.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3137-3137
Author(s):  
Matt Kalaycio ◽  
Brian J. Bolwell ◽  
Lisa Rybicki ◽  
Edward Copelan ◽  
Hien K. Duong ◽  
...  

Abstract Abstract 3137 In the absence of a matched sibling donor for allogeneic hematopoietic cell transplantation (HCT), a MUD is the most often used alternative hematopoietic cell source. Unfortunately, many patients do not have a well-matched MUD. For these patients, CBU transplant is a viable alternative donor source. To optimize hematopoietic engraftment in adult recipients two CBU are often required. We offer dCBU transplantation to patients lacking matched sibling and unrelated donors. This report compares outcomes between those treated with dCBU and MUD HCT at our institution. From 8/7/2009 through 12/2011, 22 hematologic malignancy patients received dCBU transplants using the conditioning regimen and GVHD prophylaxis described by the group at the University of Minnesota (Barker et al, Blood. 105: 1343, 2005). Thus, we treated patients with fludarabine 75mg/m2 D-8 to D-6, cyclophosphamide 120mg/kg D -7 to D -6, and total body irradiation (TBI) 1320 cGy D -4 to D -1. GVHD prophylaxis included cyclosporine and mycophenolate. We then selected 42 patients treated with MUD HCT (40 well-matched, 2 partially matched) for similar diagnoses from our database as a comparator group. Patients with MUD donors were treated with either etoposide 60mg/kg and TBI 1200cGy if they had acute lymphoblastic leukemia, or busulfan 16mg/kg orally (or the equivalent administered intravenously) D -8 to D -4 and cyclophosphamide 120mg/kg D -3 to D -2. GVHD prophylaxis for MUD patients included tacrolimus and methotrexate, except in one case where mycophenolate was substituted for methotrexate. The median age of the patients was 49 years (range 20–62 years) with no significant difference between treatment groups. Neither were there differences in diagnoses, HCT-comorbidity index, time from diagnosis to transplant, disease status, or CMV status. However, there was a significant difference with regard to race with 24% of dCBU HCT in African-American patients compared to none of the MUD HCT (P<0.001). Patients with MUD HCT recovered neutrophils and platelets faster (median 16 and 24 days respectively) compared to dCBU HCT (median 27 and 52 days respectively; P<0.001) resulting in shorter length of stay (median 29 versus 49 days; P<0.001) and contributing to a trend toward improved 100 day mortality (17% vs 38%; P=0.06). There was no significant difference in the incidence or severity for either acute or chronic GVHD between the groups. However, the incidence of infection was significantly greater with dCBU HCT (P<0.001). There was also a trend toward greater non-relapse mortality among patients treated with dCBU HCT(P=0.07) all of which occurred within the first 6 months of transplant. Cox proportional hazards analysis was used to identify univariable and multivariable prognostic factors for overall (OS) and relapse-free survival (RFS). Only age (OS: HR1.66; 95% CI 1.08–2.56; P=0.020. RFS: HR1.61; 95% CI 1.07–2.42; P=0.023) and CMV positivity in either donor or recipient (OS: HR 2.61; 95% CI 1.02–6.65; P=0.044. RFS: HR 2.71; 95%CI 1.07–6.86; P=0.035) were significant risk factors. Cell source did not significantly impact either RFS or OS (See figure). We conclude that although dCBU HCT results in increased early morbidity, there is no significant difference in risk for GVHD, and long-term survival outcomes are similar compared to MUD HCT. dCBU HCT is a useful alternative for patients lacking sibling and MUD donors. Disclosures: No relevant conflicts of interest to declare.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3073-3073
Author(s):  
Betty K. Hamilton ◽  
Brian J. Bolwell ◽  
Matt Kalaycio ◽  
Lisa Rybicki ◽  
Rabi Hanna ◽  
...  

Abstract Abstract 3073 The combination of a calcineurin inhibitor and methotrexate (MTX) is currently the gold standard for GVHD prophylaxis. MTX, however, is associated with toxicity including mucositis, delayed engraftment and other organ toxicity. We conducted a randomized trial comparing cyclosporine (CSA) and mycophenolate (MMF) with CSA and MTX for GVHD prophylaxis in recipients of myeloablative allogeneic hematopoietic cell transplants (HCT) with matched sibling donors (Bolwell et al, BMT 2004, 34:621). We showed reduced toxicity without an increased relapse rate in patients treated with MMF instead of MTX. Now, with a median follow up of almost 10 years, we report long-term outcomes of this study. From May 2001 until February 2003, 40 patients with hematologic malignancies were randomized to receive CSA (300mg/m2) and MMF (500mg three times daily) or CSA and short course MTX (5mg/m2 days 1, 3, 6, 11). Study endpoints included incidence of acute GVHD, severity of mucositis, time to engraftment of neutrophils and platelets and 100 day survival. Baseline variables were compared using the Wilcoxon rank sum tests or Chi square test. Outcomes were compared between MMF and MTX using the Pepe-Mori test. The two treatment arms were similar in patient characteristics such as age, disease, disease status, and CMV status. In total, 21 patients received MMF and 19 patients received MTX. The study was stopped early when an interim analysis demonstrated less mucositis, shorter length of stay and no difference in the incidence of GVHD or relapse with a median of 6 months of follow up. Currently, with a median follow up of 119 months (range 46–129 months) in survivors, there remains no difference in the incidence of or degree of acute (p≥0.35) or chronic GVHD (p≥0.53), overall survival (p=0.84) or relapse (p=0.41). There are 6 long term survivors in the MMF arm and 4 in the MTX arm. Of those that received MMF, 3 have mild chronic GVHD of the skin or upper GI tract and 1 has moderate chronic GVHD involving the skin, fascia, and vulva. Three of those who received MTX have mild chronic GVHD primarily of the skin. Only 3 patients (2 MMF and 1 MTX) remain off of all immunosuppression without evidence of GVHD. Eight patients (38%) died of relapse in the MMF arm versus 7 (37%) in the MTX arm which was also not statistically different (p=0.86). Death from GVHD was similar in both groups. Results from this updated analysis support our original conclusion that the combination of CSA and MMF results in decreased mucositis and more rapid engraftment compared with CSA and MTX, with no significant difference in GVHD, survival or relapse on long-term follow up. The primary limitation of this trial remains sample size and the ability to detect modest differences in survival. There remains limited data and virtually no long-term data comparing standard MTX based regimens with less toxic prophylaxis in myeloablative allogeneic HCT. Larger prospective studies with long-term follow up comparing GVHD prophylaxis regimens are warranted. Disclosures: No relevant conflicts of interest to declare.


Author(s):  
Sini Luoma ◽  
Raija Silvennoinen ◽  
Auvo Rauhala ◽  
Riitta Niittyvuopio ◽  
Eeva Martelin ◽  
...  

AbstractThe role of allogeneic hematopoietic stem cell transplantation (allo-SCT) in multiple myeloma is controversial. We analyzed the results of 205 patients transplanted in one center during 2000–2017. Transplantation was performed on 75 patients without a previous autologous SCT (upfront-allo), on 74 as tandem transplant (auto-allo), and on 56 patients after relapse. Median overall survival (OS) was 9.9 years for upfront-allo, 11.2 years for auto-allo, and 3.9 years for the relapse group (p = 0.015). Progression-free survival (PFS) was 2.4, 2.4, and 0.9 years, respectively (p < 0.001). Non-relapse mortality at 5 years was 8% overall, with no significant difference between the groups. Post-relapse survival was 4.1 years for upfront-allo and auto-allo, and 2.6 years for the relapse group (p = 0.066). Survival of high-risk patients was reduced. In multivariate analysis, the auto-allo group had improved OS and chronic graft-versus-host disease was advantageous in terms of PFS, OS, and relapse incidence. Late relapses occurred in all groups. Allo-SCT resulted in long-term survival in a small subgroup of patients. Our results indicate that auto-allo-SCT is feasible and could be considered for younger patients in the upfront setting.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4614-4614
Author(s):  
Catalina Montes De Oca ◽  
Thomas Pagliardini ◽  
Stefania Bramanti ◽  
Sabine Furst ◽  
Jean Marc Schiano de Collela ◽  
...  

Introduction: allogeneic transplantation (allo-HSCT) is a curative treatment for patients with advanced lymphoma. Haploidentical (haplo-SCT) transplantation extended the accessibility to allo-HSCT, overcoming the issue of donor availability. However, alternative donor allo-HSCT is still considered at higher risk of non-relapse mortality due to the HLA disparity and thus an anticipated higher incidence of GVHD. In this context, the use of a non myeloablative conditioning (NMAC) regimen combined with post transplantation cyclophosphamide (PT-Cy) based GVHD prophylaxis may reduce procedure related toxicity. The aim was to evaluate the toxicity and efficacy of haplo-SCT using NMAC with PT-Cy in advanced lymphoma patients. Methods: We here report the retrospective experience of a bicentric transplantation program. We analyzed a cohort of lymphoma patients undergoing Haplo-SCT and homogeneously receiving NMAC and PT-Cy. Inclusion criteria were: 1) first allo-HSCT for advanced lymphoma between 2009 and 2018; 2) haploidentical donor; 3) NMAC (fludarabine cyclophosphamide and 2 gray TBI GVHD prophylaxis consisted of PT-Cy day+3 and +4 , cyclosporine A and MMF starting from day +5. Multivariate analyses included age, disease type (NHL vs HL), HCT-CI (< vs ≥ 3), graft source (PBSC vs BM), disease status at haplo-SCT (CR vs other). Results: One hundred forty seven patients (73 NHL; 74 HL) with a median age of 46 years (range: 19-71) were included. PBSC (peripheral blood stem cell) was used as graft source in 96 patients (65%). Patients received a median number of 3 conventional chemotherapy lines before haplo-SCT (1-8). Sixty-five (44%) had relapse after Auto-HCT. At the time of haplo-SCT, 96 patients (66%) were in complete remission. The cumulative incidences of day+100 grade 2-4 and 3-4 acute GVHD were 30% and 3%, respectively. The cumulative incidences of 2-year chronic and moderate or severe chronic GVHD were 13% and 8%, respectively. With a median follow up of 39 months (6-114), 2-year NRM was 14%, with a trend for higher risk in patients with HCT-CI ≥ 3 (HR 0.39, 95CI [0.15-1.04] p = 0.061) while age was not associated with an increased risk of NRM (HR 1.01, 95CI [0.98-1.05], p = 0.450). Two-year cumulative incidence of relapse (CIR) was 21% and 18% in HL and NHL patients, respectively. Disease status at the time of haplo-SCT was strongly associated with relapse (HR 2.99, 95CI [1.41-6.35], p = 0.004) In HL patients, 2-year PFS, OS and GRFS were 65%, 77% and 57%, respectively, while corresponding values in NHL patients were 65%, 69% and 55%, respectively. Two-year PFS and GRFS were significantly higher in patients who underwent haplo-SCT in CR (PFS: CR vs. no CR: 72% vs. 55%, p=0.045; GRFS: CR vs. no CR: 63% vs. 42%, p=0.010). There was a trend for better 2-year OS in CR (OS: CR vs. no CR: 78% vs. 63%, p=0.063. Conclusion: We confirm the feasibility of haplo-SCT using NMAC and PT-Cy with low incidence of GVHD (notably severe forms) and NRM. In addition, we observed a relatively low incidence of relapse (19%) in this cohort of heavily pretreated patients, underlining a potent graft-versus-lymphoma effect after haplo-SCT, leading to promising survivals, including high rate of GRFS (>50%), suggesting a preserved long term quality of life in survivors. We conclude that NMAC haplo-SCT with PT-Cy should be considered as a valuable curative option for advanced lymphoma patients, with a favorable toxicity profile and promising long term survival. Figure Disclosures Stoppa: celgene: Other: travel fees, lecture fees; takeda: Other: travel fees. Carlo-Stella:MSD: Honoraria; BMS: Honoraria; Janssen: Other: Travel, accommodations; Boehringer Ingelheim: Consultancy; Genenta Science sr: Consultancy; Sanofi: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Other: Travel, accommodations, Research Funding; Novartis: Consultancy, Research Funding; Servier: Consultancy, Honoraria, Other: Travel, accommodations; F. Hoffmann-La Roche Ltd: Honoraria, Other: Travel, accommodations, Research Funding; Rhizen Pharmaceuticals: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Takeda: Other: Travel, accommodations; Janssen Oncology: Honoraria; AstraZeneca: Honoraria. Chabannon:EBMT: Other: Working Party Chair, Board member; Fresenius Kabi: Other: research support; Miltenyi Biotech: Other: research support; Terumo BCT: Other: speaker's fees; Celgene: Other: speaker's fees; Novartis: Other: speaker's fees; Gilead: Other: speaker's fees, hospitalities; Sanofi SA: Other: research support, speaker's fees, hospitalities. Santoro:Takeda: Speakers Bureau; BMS: Speakers Bureau; Roche: Speakers Bureau; Abb-Vie: Speakers Bureau; Amgen: Speakers Bureau; Celgene: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Gilead: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Arqule: Consultancy, Speakers Bureau; Lilly: Speakers Bureau; Sandoz: Speakers Bureau; Eisai: Consultancy, Speakers Bureau; Novartis: Speakers Bureau; Bayer: Consultancy, Speakers Bureau; MSD: Speakers Bureau; BMS: Consultancy. Blaise:Sanofi: Honoraria; Jazz Pharmaceuticals: Honoraria; Molmed: Consultancy, Honoraria; Pierre Fabre medicaments: Honoraria.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4655-4655 ◽  
Author(s):  
Kavita Raj ◽  
Eduardo Olavarria ◽  
Diderik-Jan Eikema ◽  
Liesbeth C de Wreede ◽  
Linda Koster ◽  
...  

Abstract Background: Allogeneic stem cell transplantation is a treatment option for patients with advanced myelofibrosis. Problems encountered include an increased risk of delayed or poor engraftment and in the mismatched unrelated donor setting a higher rate of GVHD and particularly poor outcomes. As for other indications for allogeneic stem cell transplants, patients for whom either a matched sibling or matched unrelated donor is not available are considered for either a double umbilical cord blood, a mismatched unrelated donor or haploidentical stem cell transplant. Data on the latter option are limited and we reviewed registry data on all family mismatched donor transplants performed between 2001 and 2015 and reported to the EBMT registry. Results: Records retrieved 69 patients with myelofibrosis transplanted between November 2001 and November 2015. 44 (64%) were male. 50 (74%) had primary myelofibrosis,18 (27%) had secondary myelofibrosis (6 from ET, 5 from PRV and 7 others) and unknown 1(2%). Of 25 patients for whom the JAK2 V617F mutation status was known, 15 (22%) harboured the mutation. Patient Karnofsky performance status was > 70% in 98%. Of the mismatched family donors, 47 (68%) were male and 22 (31%) female. Donors were HLA mismatched at 1 locus in 12 (17%) and 2 or more loci in 48 (69%). Donor-recipient serology combinations were CMV -/- in 8 (12%), +/- in 4 (6%), -/+ in 15 (22%) and +/+ in 34 (49%) missing 8 (12%). Bone marrow was the stem cell source in 34 (49%) and peripheral blood in 35 (51%). The median total nucleated cell count (TNC) infused was 7.5x108/kg (range 2.3-21x108/kg) from data available in 17 patients. The median CD34+ cell dose was 6.9x106/kg (range 1.9-18.18x106/kg) from data available in 19 patients. Conditioning was myeloablative in 48 (70%) and RIC in 21 (30%) The conditioning regimes were varied but the predominant ones were Fludarabine, Busulphan, ATG (FBATG) and Thiotepa, Busulphan, Fludarabine (TBF). TBI was administered in 8 (12%) and in vivo T cell depletion in 22 (32%), ex-vivo T cell depletion in 5 (7%) patients. GVHD prophylaxis varied with post transplant Cyclophosphamide administered in 34/67 (49%) and ATG in 19/67 patients (28%). Neutrophil engraftment was established in 53 (82%) at a median of 20 days (range 11-83). Primary graft failure occurred in 8 (12%) and secondary graft failure in 4 (6%). This occurred at a median of 12 months (range 4.5-35 months). Eleven of these patients had a second allograft at a mean interval of 6.4 months. Responses to the first allograft (censoring for patients who had a second allograft) with data available in 45 patients, showed that complete remission was achieved in 35 patients (78%), 6 (13%) were never in CR and 4 (9%) were not evaluable. The cumulative incidence of grade II-IV acute GvHD at 100 days was 12% (95% CI 4-21%) and for grade III-IV acute GvHD at 100 days it was 5% (95% CI 3-11%). Data for chronic GVHD was valid in 49 patients. The cumulative incidence of chronic GvHD at 2 years was 62% (95% CI 47-76%). The cumulative incidence of limited cGvHD was 45% (95% CI 31-59%) whereas the cumulative incidence of extensive cGvHD was 10% (95% CI 2-19%). The median follow up was 24 months (95% CI 13-35 months). The 2-year OS was 51% (95% CI 37-76%) and the 5-year OS was 38% (95% CI 21-55%). The 2-year RFS was 44% (95% CI 30-59%) and the 5-year RFS was 31% (95% CI 15-48%). The 2 year cumulative incidence of relapse was 14% (95% CI 5-24%). The 2 year NRM was 41% (95% CI 28-55%), which increased to 54% (95% CI 37-72%) at 5 years. The main causes of death were infection (16, 24%), GVHD (7, 10%) organ damage or failure (3, 5%), relapse/disease progression (1, 2%) and secondary malignancy or PTLD (1, 2%). On univariate analysis there was no significant effect of recipient gender, donor gender, degree of HLA mismatch 1 vs >1 Ag MM, CMV matching between donor and recipient, primary or secondary MF, disease stage at transplant (chronic versus advanced phase), conditioning intensity, conditioning regimen, GVHD prophylaxis with ATG or post transplant cyclophosphamide or stem cell source on overall survival. Conclusion: Concerns regarding engraftment and secondary graft failure have excluded patients with myelofibrosis from clinical trials of mismatched related donor transplant. The data suggest that engraftment is feasible, and PFS and OS can be attained with limited severe chronic GVHD with family mismatched donors in this setting. Disclosures Ciceri: MolMed SpA: Consultancy.


Blood ◽  
1995 ◽  
Vol 85 (9) ◽  
pp. 2354-2363 ◽  
Author(s):  
J Casper ◽  
B Camitta ◽  
R Truitt ◽  
LA Baxter-Lowe ◽  
N Bunin ◽  
...  

Allogeneic bone marrow transplantation is the treatment of choice for many childhood leukemias. The donor of choice-an HLA matched sibling-is only available about 30% of the time. Unrelated donors are an alternative choice. In this report, we describe the results of unrelated donor bone marrow transplants (BMT) in 50 children with leukemia (25 acute lymphoblastic leukemia [ALL], 3 acute myeloid leukemia [AML], 3 juvenile chronic myelogenous leukemia [JCML], 10 chronic myeloid leukemia [CML]) or myelodysplastic syndrome (MDS; 9). The median age of the 31 male and 19 female patients was 9 years (range 2 to 18). Only 13 patients were serologically matched at HLA-A, B, DR, and DQ with their donors; 6 of these were reactive in mixed lymphocyte culture. The other 37 patients were mismatched for one (36 patients) or more (1 patient) HLA antigens. Pretransplant conditioning included cytosine arabinoside, cyclophosphamide, fractionated total body irradiation (TBI) (with lung, liver, and more recently, kidney shielding), and methylprednisolone. High-risk patients also received busulfan. Graft-versus-host disease (GVHD) prophylaxis consisted of T- cell depletion with IgM monoclonal antibody T10B9 plus complement and posttransplant cyclosporine-A. Forty-nine patients (98%) engrafted. Median times to greater than 500 polymorphonuclear leukocytes (PMN)/microL and greater than 25,000 platelets/microL were 18 and 20 days, respectively. Acute GVHD > or = grade II occurred in 16 patients (33%); 13 (81%) of these died. Chronic GVHD developed in 30 of 40 patients at risk, but was extensive in only 5. Event-free survival (EFS) for all patients was 44% +/- 7% (median follow-up was 49 months), and overall survival was 50 +/- 7%. Patients with low-risk disease (ALL or AML in first or second remission and CML in chronic phase) had a better EFS than children with high-risk disease (60% v 34%, P = .07). There was no significant difference in EFS between patients who were serologically matched with their donors (46%) and those who were partially mismatched (43%) (P = .97). These data compare favorably with published reports for children transplanted with HLA-matched sibling donors and should encourage earlier consideration of unrelated donor BMT in children with leukemia or myelodysplasia.


2019 ◽  
Vol 32 (Supplement_2) ◽  
Author(s):  
R Alfieri ◽  
M Nardi ◽  
V Moretto ◽  
E Pinto ◽  
M Briarava ◽  
...  

Abstract Aim To investigate whether preoperative malnutrition is associated with long term outcome and survival in patients undergoing radical oesophagectomy for oesophageal or oesophagogastric junction cancer. Background & Methods Dysphagia, weight loss, chemo-radiationtherapy frequently lead to malnutrition in patients with oesophageal or oesophagogastric junction cancer. Severe malnutrition is associated with higher risk of postoperative complications but little is known on the correlation with long term survival. We conducted a single center retrospective study on a prospectively collected database of patients undergoing oesophagectomy from 2008 and 2012 in order to evaluate the impact of preoperative malnutrition with postoperative outcome and long term survival. Preoperative malnutrition was classified as: prealbumin level less than 220 mg/dL (PL), MUST index (Malnutrition Universal Screeening Tool) >2 and weight loss >10%. Results 177 consecutive patients were considered: due to incomplete data 60 were excluded from the analysis that was performed on 117 patients. PL was reported in 52 (44%) patients, MUST index was recorded in 62 (53%), 58 (49%) patients presented more than 10% weight loss at the preoperative evaluation. PL was associated with more postoperative Clavien-Dindo 1-2 complications (p=0.048, OR 2.35 95%IC 1.001-5.50), no differences were observed in mortality, anastomotic leak, major pulmonary complications. MUST index was not correlated with postoperative complications nor mortality but resulted worse in patients treated with chemo-radiotherapy (p=0.046, OR 1.92 95%CI 1.011-3.64). Weight loss >10% was not associated with postoperative complications or mortality. Overall 7 years survival rate was 69%. and DFS was 68%. Malnourished patients did not differ from non-malnourished regarding age, sex, tumor site, tumor stage and histology. No significant difference in 7 years survival rates was observed in patients with PL <220 mg/dL ( 55 % vs 67%), neither in patients with MUST score>2 (58% vs 72%), nor in patients with weight loss >10% (53% vs 70%). Conclusions Malnutrition is more common in patients treated with chemoradiation therapy and it is associated with postoperative complications. However, both long term and disease free survival are not affected by preoperative nutritional status. Larger patient population and data on long term postoperative nutritional status will be analyzed in further studies.


Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1128-1128 ◽  
Author(s):  
Paolo Corradini ◽  
Anna Dodero ◽  
Marco Bregni ◽  
Francesco Zallio ◽  
Lucia Farina ◽  
...  

Abstract Patients with relapsed PTCL have a poor prognosis. We had previously shown the existence of a graft-versus-lymphoma effect against PTCL (J Clin Oncol, 2004). In the present report, we extended our previous observations to 26 patients (pts) receving allo-SCT. All patients received several courses of debulkying chemotherapy (usually 3 DHAP and/or high-dose chemotherapy) followed by the same RIC regimen containing thiotepa (10 mg/kg), fludarabine (60 mg/ms) and cyclophosphamide (60 mg/kg). GVHD prophylaxis consisted of cyclosporine A and short-course methotrexate. Patients’ median age was 45 years (range, 15–64). Histologic PTCL subtypes included: PTCL not otherwise specified (n=12), ALCL (n=7), angioimmunoblastic (n=3), others subtypes (n=4). Twenty-two pts (84%) received transplant from HLA-identical sibling, 3 from haploidentical sibling and one from unrelated donor. The median time from diagnosis to transplantation was 17 months. Thirteen patients (50%) had failed a previous auto and the majority received at least 2 lines of chemotherapy before allo-SCT. Seven (27%) and 13 pts (50%) were in CR and PR at the time of allo-SCT, respectively. At median follow-up of 27 months (range, 8–73), 17 (65%) were alive (n=14 in CR) and 9 died (n=6 disease, n=3 toxicity). The estimated 3-year TRM was 13%. The estimated 5 year OS and PFS projections were 61% (95% CI, 41–81%) and 51% (95% CI, 30–72%), respectively. Relapses occurred in the first 6 months after allo-SCT and we did not observe differences in PFS between specified and unspecified variants. De-novo acute GVHD (II/IV) and chronic GVHD incidence were 28% and 24%, respectively. Eight patients received DLI, 6 for relapse, 1 pre-emptive, 1 for infection: 3 responded (n=1 CR, n=2 PR). Following DLIs, 4 patients developed GVHD with associated a clinical response. In conclusion, our data indicate: 1) long-term disease control was achieved in patients with an aggressive subtype of NHL; 2) although optimal therapeutic strategies for relapsed PTCL are yet to be defined, further prospective evaluation of allo-SCT is required.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2013-2013 ◽  
Author(s):  
Gertjan J. Kaspers ◽  
M. Zimmermann ◽  
G. Fleischhack ◽  
R. Tamminga ◽  
Brenda Gibson ◽  
...  

Abstract Relapse occurs in 30–40% of newly diagnosed AML patients, with long-term survival in 20%. Aiming at improved outcome, we initiated a prospective, randomised study for relapsed AML, excluding AML M3 and those >18 years of age at initial diagnosis. FLAG is being used for 2 consecutive courses: fludarabine 30 mg/m2/day x 5, cytarabine 2 g/m2/day x 5, G-CSF 200 μg/m2/dose for 6 days, starting day -1. Liposomal daunorubicin (DaunoXome, DNX) is a new anthracycline with potentially less cardiotoxicity. Therefore, DNX at 60 mg/m2/day on days 1, 3 and 5 was randomly added or not to the first course of FLAG. Main objectives are to determine the efficacy and toxicity of DNX when added to FLAG, and the long-term outcome in a large group of relapsed AML patients. Thirteen groups worldwide are enrolling patients. More than 400 patients were registered by March 2006. This planned 2nd interim analysis with blinded efficacy data concerns 322 eligible and evaluable patients with first relapsed AML, of whom 250 (78%) were actually randomised. Fifty-two percent of patients relapsed early (<1 year from initial diagnosis). The majority (84%) concerned isolated bone marrow relapse, with central nervous system involvement in 6% of all patients. Dominating FAB types are M2 with auer rods, M4 without eosinophils and M5. Poor response to the 1st course of therapy (>20% of blasts in the BM shortly before the 2nd course), was seen in 23% of patients, more often in early relapses (31%) than in late relapses (15%). Early death occurred in 6% of patients. Complete remission (CR) was achieved in 63% of patients after 2 courses, and they have a probability of survival at 3 years (3-yr pSurv.) of 47% compared to 33% for the total group and 8% for patients not achieving CR. Compared to early relapses, patients with late relapse had higher CR rates (76 vs 51%), and higher 3-yr pSurv.: 42% vs 23%. Similarly, patients with either t(8;21) or inv(16) had a significantly better outcome. Death in continuous CR occurred in 8.6% of 322 patients, without excess of deaths in one treatment arm. Nearly all patients in CR have been transplanted, the majority with a matched unrelated donor. There was significant grade III/IV toxicity, but no unexpected toxicity, and no clinically relevant differences between the arms with and without DNX, especially not in cardiotoxicity. In conclusion, it is feasible to perform a large randomised pediatric study in a very international setting. DNX added to FLAG does not result in major additional toxicity, but follow-up of cardiotoxicity should be extended as planned in this protocol. Late relapses do better in terms of CR and overall survival, as well as patients with t(8;21) or inv(16), but early relapses achieving CR have a realistic chance of survival as well with currently 23% of them in continuous CR. The study is ongoing until 360 eligible and fully evaluable patients have been randomised, to answer the question whether liposomal daunorubicin improves outcome in pediatric relapsed AML.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4765-4765
Author(s):  
Ashutosh D. Wechalekar ◽  
Helen J. Lachmann ◽  
Julian D. Gillmore ◽  
Philip N. Hawkins

Abstract AL amyloidosis has a poor outcome. Survival of only about one year was frequently reported in studies performed in the 1990s, and the diagnosis of AL amyloidosis continues to be widely regarded as incompatible with long term survival. We report here the features of patients with AL amyloidosis followed up at the UK Amyloidosis centre (NAC) for more than 10 years, who encouragingly represented more than 10% of all cases. All patients with AL amyloidosis who first attended the NAC between 1979–1997 and subsequently survived for more than 10 years were included in this study. AL type amyloidosis was confirmed in all patients histologically with genetic studies to robustly exclude hereditary amyloidosis as indicated. Organ involvement and responses were defined as per the international consensus criteria (Gertz et al 2005). I123 serum amyloid P (SAP) scintigraphy was used to identify additional organ involvement and monitor amyloid load. 361 patients with AL amyloidosis were assessed at the NAC before 1st August 1997, with a median survival of 2.4 yrs. 132 (20%) patients survived >5 yrs, and 44 (12%) patients survived >10 years with 2 patients living ≥ 16 yrs and 7 for ≥ 14 yrs. Three patients died at 10.2, 11 and 13 years due to unrelated causes with no deaths due to progressive amyloidosis. Among the 44 ten year survivors, at presentation, median age was 51 yrs (29–70), median creatinine 86μmol/L (47–400), 24 hour proteinuria 2g (<0.1g–50g), bilirubin 8μmol/L (2–130), alkaline phosphatase 82.5 units/L (41–2645), and median NT-ProBNP 19 pMol/L (1–2158). Median ECOG performance status was 1 (0–2). Organ involvement (consensus criteria) was: renal 31 (70%); liver 6 (14%); cardiac 8 (18%); autonomic neuropathy 1(2%); peripheral neuropathy - none; gastrointestinal 2(4%) and lymph nodes or other soft tissues 4 (9%). SAP scintigraphy showed renal amyloid deposits in 30 (68%), liver 11(25%), adrenals 3(7%) and bone infiltration 7 (16%). 35 (79%) had one organ involved, 8 (18%) had 2 organs and 1 (3%) patient had three organs involved by consensus criteria; SAP scintigraphy detected additional organ involvement in 12 cases (27%). The whole body amyloid load on SAP scintigraphy was small in 25(57%), moderate 2 (4%) and large 9 (21%). Median plasma cell infiltrate in the marrow was 5% (1–65). Treatment received comprised an alkylator based regimen in 11(26%), VAD chemotherapy in 14 (32%), and stem cell transplantation (SCT) in 18 (42%). 29 (67%) patients had a complete clonal response, 13 (30%) had a partial response and 1 (2%) had no response. 25(57%) had evidence of organ improvement by conventional criteria and in 26 (59%) SAP scintigraphy showed regression of amyloid. The median time to next treatment (progression free survival - PFS) has not been reached at 10 yrs. There was no significant difference in the PFS between patients treated chemotherapy or SCT, or among the complete or partial responders. 13 patients (30%) developed end stage renal disease (ESRD) a median 5.8 yrs after diagnosis and this was not significantly more frequent among partial responders compared with complete hematologic responders. Substantial improvements in diagnosis, monitoring and treatment of AL amyloidosis have occured since 1997. It is all the more encouraging that we are able to report here that 12% of patients diagnosed before this time survived for more than 10 years and patients with AL amyloidosis diagnosed more recently are likely to have even better prospect of good long term outcome in cases who achieve good and sustained clonal responses to therapy.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2771-2771 ◽  
Author(s):  
Ryotaro Nakamura ◽  
Joycelynne Palmer ◽  
Pablo Parker ◽  
Anthony Stein ◽  
Tracey Stiller ◽  
...  

Abstract Abstract 2771 Poster Board II-747 We previously reported an encouraging result with RI-HCT for MDS (Bone Marrow Transplant 2007; 40:843-50) using flugarabine/melphalan conditioning and cyclosporine (CSA)/mycophenolate (MMF) as GVHD prophylaxis. In order to further improve upon the outcome in the RI-HCT setting, we initiated a series of clinical trials at City of Hope National Medical Center designed to evaluate the impact of tacrolimus (FK)/sirolimus (SIRO)-based GVHD prophylaxis. Here we report the combined, updated results from a consecutive case-series of 89 patients with MDS (including AML progressed from MDS) who underwent RI-HCT from 2000 to 2008 and received either CSA/MMF (n =44) or FK/SIRO (n=45)-based GVHD prophylaxis. All patients received fludarabine 125 mg/m2 plus melphalan 140 mg/m2 followed by an allogeneic HCT (peripheral blood: n=83, bone marrow: n=6) from an HLA-identical sibling (SIB: n=35) or unrelated donor (MUD: n=54). Additional ATG was given to 12 patients. For MUD transplants a short course of methotrexate was added to CSA/MMF or FK/SIRO. The median age was 59 years (range: 20-71) and 31 (35%) patients were female, 58 (65%) were male. Diagnoses at transplant were RA (n=21), RARS (n=1), RAEB/RAEBT (n=36), and AML from prior MDS (n=31). Cytogenetic risk was low in 15 (17%), intermediate in 37 (41.5%), high in 37 (41.5%) patients. By IPSS criteria (for MDS only), 2 patients had low, 24 had int-1, 20 had int-2, and 12 had high-risk MDS. Twenty-seven patients had therapy-related MDS including 14 with prior autologous HCT. The median follow-up time for surviving patients was 39 months (range: 24-68) for the CSA/MMF group and 17 months (range: 4-39) for the FK/SIRO group. All but two patients (1 in CSA/MMF, 1 in FK/SIRO) engrafted with the median neutrophil recovery at 15 days (range: 11-55). The baseline patient, disease and transplant characteristics were similar between CSA/MMF and FK/SIRO, except for an increased percentage of therap-related MDS in the CSA/MMF group (43% vs. 18%, p<0.01). The median donor chimerism by STR at day 30 post-transplant was 100% in both groups (p=0.6). FK/SIRO was associated with a significantly reduced one-year non-relapse mortality (NRM) (11.4%) compared with CSA/MMF (36.2%, p=0.01). This improvement in NRM translated into a trend for improved overall survival (81.4% vs. 52.3%, p=0.1) and disease-free survival (72.2% vs. 52.3%, p=0.08) at one year. While we observed no significant difference in acute GVHD grade II-IV between CSA/MMF and FK/SIRO, FK/SIRO was associated with a significant reduction in grade IV GVHD (0% versus 26%, p<0.01) and a trend for III-IV GVHD (31% vs. 55%, p=0.1). There was no significant difference in chronic GVHD between FK/SIRO (60%) and CSA/MMF (56%, p=0.8). In multivariate analysis, the use of FK/SIRO was independently associated with improved NRM after adjusted for donor type, therapy-related MDS, %bone marrow blasts, and HLA match status (Table). In conclusion, FK/SIRO-based GVHD prophylaxis was associated with an improved outcome after RI-HCT for MDS attributable to the reduced risk for severe acute GVHD.Variables for NRMHazard Ratio (95% CI)p-valueDe novo (n=62) Therapy-related (n=27)baseline 0.75 (0.31–1.89)0.55Sibling donor (n=35) Unrelated donor (n=54)baseline 2.17 (0.70–6.74)0.18Bone marrow blasts < or =10% (n=67) Bone marrow blasts >10% (n=22)baseline 2.13 (0.92–4.96)0.08HLA match (sibling donor or 10/10 MUD, n=72)HLA < mismatch MUD (<10/10 match, n=17)baseline 6.26 (2.11–18.55)0.001FK/SIRO (n=45) CSA/MMF (n=44)baseline 6.58 (2.15–20.14)0.001 Disclosures: Off Label Use: cyclosporine, cellcept, tacrolimus, sirolimus, and methotrexate for GVHD prophylaxis.


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