Outcome Of Chronic Lymphocytic Leukemia (CLL) Patients That Failed Allogeneic Stem Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2880-2880
Author(s):  
Ohad Benjamini ◽  
Uri Rozovski ◽  
Preetesh Jain ◽  
William G. Wierda ◽  
Susan O'Brien ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Treatment Modality ◽  
Treatment Options ◽  
Salvage Treatment ◽  
Treatment Regimens ◽  
Immune Manipulation ◽  
Btk Inhibitor

Abstract Introduction Allogeneic hematopoietic stem cell transplantation (allo-SCT) has become a therapeutic option for patients (pts) with high risk CLL. The major cause of allo-SCT failure is relapse or disease progression. No standard treatment is available for pts who failed allo-SCT and post-SCT immune manipulation, and the prognosis of these pts is largely unknown. Methods We performed a retrospective intention-to-treat analysis of pts with CLL who failed allo-SCT and post-SCT immune manipulation between 1998 and 2012 and were referred to the Leukemia Department at MD Anderson Cancer Center for further treatment. Results Seventy-three pts with CLL (n=40, 55%) or Richter's transformation (RT, n=33, 45%) who failed or progressed after allo-SCT were referred for further management at a median of 7 months (range 0-85 months) after allo-SCT. Most pts (n=63, 86%) had received non-myeloablative conditioning and 32 (44%) received post allo-SCT donor lymphocyte infusion (DLI). Six patients (8%) had early (4 pts) or late (2 pts) graft failure. Fifty four (74%) pts were male and the median age at time of failure/progression was 59 yrs (range 32–73 yrs). Of the 73 pts, 68 (93%) received salvage therapy, 1 pt died before treatment was initiated, and 4 pts were considering treatment options at time of last follow-up. A median of 2 treatment regimens (range 0 - 8) were administered between time of post-SCT progression and last follow-up. The most common salvage treatment regimens were chemo-immunotherapy with rituximab (R): R-HyperCVAD (n=24, 33%), OFAR (n=13, 18%), FCR, FBR, PCR, BR (n=24, 33%), immune-modulators thalidomide or lenalidomide (n=21, 29%), alemtuzumab with or without chemotherapy (n=12, 16%), and Bruton's Tyrosine Kinase (BTK) inhibitor (n=5, 7%). At time of last follow up, 26 pts (36%) were alive. The median overall survival (OS) from time of progression after allo-SCT was 33 months (95% CI, 27– 39) and 60% of the pts were alive 2 years from time of progression. Median OS after allo-SCT failure/progression was 53 months (95% CI, 9–97) for CLL pts and 28 months (95% CI, 12–44) for pts with RT (Log Rank: P<0.0001) (Figure 1). Only 4 pts achieved CR following first salvage treatment. The OS of these pts was 152, 41, 26+, 38+ months (the latter 2 are still alive). Pts with partial response (PR), no-response (NR) or progression after first salvage treatment had similar OS. To identify the best treatment modality we analyzed the OS from progression and from time of initiation of treatment to last follow-up of all regimens used. We found that patients treated with either FCR, alemtuzumab or combination chemotherapy did not have significant difference in OS. Remarkably, 4 of 5 pts treated with BTK inhibitor were alive at time of last follow-up. Univariable analyses showed shorter OS for pts with a higher ECOG performance status (PS; P=0.036), low hemoglobin (Hb) (P=0.0001), low albumin (P=0.0001), complex cytogenetic abnormalities at last follow up (P=0.026) and RT (P=0.0001). The multivariable Cox model analyses including age, sex, previous DLI, unfavorable cytogenetic abnormalities before or after allo-SCT, albumin, absolute lymphocyte count and platelet count, identified only Hb (P=0.009, 95% CI; 0.58 - 0.93), ECOG 3 (P=0.036, 95% CI; 1.12 - 30.04) and RT (P=0.002, 95% CI: 1.51 - 6.50) as independently associated with shorter OS. Conclusions The median OS of pts with high-risk CLL or RT from time of allo-SCT failure/progression was 33 months. The longest OS was observed in pts who attained CR after first salvage treatment (4/73, 6%). At the time of analysis, the 50% OS of pts treated with BTK inhibitors was not reached, however, no treatment modality appeared to be superior. Future studies of treatment options for pts that progress after allo-SCT are warranted. Disclosures: Off Label Use: Ibrutinib for CLL therapy.

Life after Fludarabine, Cyclophosphamide, & Rituximab (FCR) - the Clinical Outcome of Patients with Chronic Lymphocytic Leukemia Who Receive Salvage Treatment after Frontline FCR.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2090-2090 ◽  
Author(s):  
Constantine S. Tam ◽  
William G. Wierda ◽  
Susan O’Brien ◽  
Susan Lerner ◽  
Issa F Khouri ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Allogeneic Stem Cell Transplantation ◽  
Salvage Treatment ◽  
Refractory Disease ◽  
Second Line ◽  
Second Line Therapy ◽  
Line Therapy

Abstract The FCR regimen is the most active treatment program in CLL, with 72% of frontline patients achieving a complete remission (CR) lasting a median of 7 years. However, most patients are not cured and will eventually relapse with CLL. In order to evaluate how these patients should be subsequently managed, we analyzed our institutional experience with 300 patients treated with frontline FCR (Blood 112:975). After a median follow-up of 6 years, 116 patients (39%) had failed FCR therapy with 13 primary refractory disease and 103 relapses from partial remission (PR), nodular PR (nPR) or CR. Compared with patients in ongoing remission, relapsed/refractory patients had more adverse baseline characteristics including a greater proportion with performance status ≥ 1 (71% vs 53% p=0.002), elevated β2m (54% vs 36% p=0.002), white cell count ≥ 150 x 10^9/L (25% vs 12% p=0.003), unmutated IgVH (81% vs 44% p&lt;0.001) and ZAP-70 positivity (78% vs 49% p&lt;0.001). The aim of the current analysis was to determine the duration of survival (OS) following second-line therapy in 97 patients who had completed salvage treatment. The median follow-up was 32 (range 3 – 69) months, and the median OS (mOS) was 32 months. Characteristics associated with favorable OS were: (1) previous best response to FCR of nPR/CR lasting ≥ 18 months (mOS 47 months, vs 13 months for primary refractory disease, PR or nPR/CR lasting &lt;18 months p=0.002); (2) β2m &lt; 3.0 mg/L (mOS not reached, vs 17 months p=0.0003) and (3) platelets ≥ 100x10^9/L (mOS 47 months, vs 15 months p=0.004). Poor risk cytogenetic abnormalities were common at FCR failure: among 38 assessable patients, 7 (18%) had 17p- and 18 (47%) had 11q- by conventional karyotyping and/or FISH. Although patients with 17p- or 11q- had an inferior survival, this survival disadvantage was confined entirely to those who also had an elevated β2m ≥ 3.0 mg/L. Surprisingly, patients relapsing after durable FCR remissions (≥ 5 years) and patients with slowly progressive relapse (time to salvage ≥ 12 months after FCR failure) had similar OS as their more adverse counterparts (p=0.76 and 0.86 respectively). A prognostic model comprising β2m and platelet count effectively divided patients into low, intermediate and high risk categories with mOS of &gt;45, 32 and 13 months respectively (p&lt;0.0001). Patients received treatment chosen at the discretion of individual treating physicians and the CR rate of second-line therapy were: FCR (n=30), 17%; rituximab (n=25), 4%; alemtuzumab ± rituximab (n=16), 31%; FCR & alemtuzumab (CFAR, n=9), 56%; lymphoma-type chemotherapy (n=5), 0%; other treatment (n=12), 0%. The CR rate for CFAR was significantly higher than that of FCR (p=0.03), although the median remission duration (30 vs 20 months) and OS (44 vs 32 months) were similar (p=0.87 and 0.51 respectively). None of the regimens showed a significant survival benefit. Allogeneic stem cell transplantation (SCT) was performed in 27 (28%) patients at a median of 15 months after first salvage. Patients receiving SCT had a significantly superior OS than those who did not undergo SCT (not reached vs 30 months, p=0.03). Of the 14 patients surviving for more than four years, 11 (79%) had undergone a SCT. Patients who fail FCR therapy had high risk disease features including elevated β2m, unmutated IgVH and ZAP-70 positivity, and most had adverse cytogenetic findings at relapse. Results of salvage therapy in this group were poor with a median survival of less than three years. The majority of long-term survivors had received allogeneic stem cell transplantation.

scholarly journals Survival Comparison of Three Treatment Regimens of POEMS Syndrome: A Single-Center Retrospective Study

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3428-3428
Author(s):  
Hao Zhao ◽  
Xufei Huang ◽  
Hao Cai ◽  
Lu Zhang ◽  
Jun Feng ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Complete Remission ◽  
Stem Cell Transplantation ◽  
Subgroup Analysis ◽  
Poems Syndrome ◽  
Treatment Regimens ◽  
Remission Rates ◽  
Risk Patients

Abstract OBJECTIVE: POEMS syndrome is a rare plasma cell dyscrasia and there is currently no standard treatment. Current treatments include melphalan, autologous stem cell transplantation (ASCT) and novel regimens. However, the efficacy of these treatments has not previously been retrospectively compared in large cohorts. Therefore, this study aims to compare the efficacy and survival of three treatment regimens in patients with POEMS syndrome in our 18-year cohort. METHODS: We retrospectively analyzed the clinical records of 347 patients with newly diagnosed POEMS syndrome who were diagnosed and treated in our hospital from January 2000 to December 2017 with complete treatment and follow-up data. Patients were divided into three groups according to the initial first-line treatment regimen: melphalan + dexamethasone (MDex, N = 79) for 9 months, autologous stem cell transplantation (ASCT, N = 165), or lenalidomide + dexamethasone for 1 year (LDex, N= 103). Hematologic complete remission rates (CRH), vascular endothelial growth factor (VEGF) complete remission rates (CRV), and neurological remission rates (RN) were compared for three regimens, as well as progression-free survival (PFS) and overall survival (OS). Hematologic complete remission was negative IFE and no FLC in serum or urine. The VEGF complete remission was normalized VEGF (<600 pg/ml). The neurological response was defined as the reduction of ONLS by more than 1 point. Remission rates were compared by Pearson ӽ 2 test or Fisher's exact test. Survival curves were plotted by the Kaplan-Meier method and tested using a log-rank test. Subgroup analyses were based on risk stratification and heterogeneous baseline characteristics between treatment groups. RESULTS: Patients in the ASCT group achieved significantly higher rates of CRV (66.2%), which were superior to the MDex group (38.5%, p = 0.001) and the LDex group (47.7%, p = 0.006). There were no significant differences in CRH and RN between the three groups: CRH (MDex 37.7% vs ASCT 49.7% vs LDex 47.5%, p = 0.244) and RN (MDex 100% vs ASCT 91.% vs LDex 93.8%, p = 0.234). However, the proportion of low risk patients in the ASCT group was significantly higher than that in the MDex and LDex groups (44.2% vs 22.8% & 26.2%, p=0.001). Therefore, we performed a subgroup analysis. Subgroup analysis showed that the CRV in the ASCT group was similar to that in MDex and LDex groups in the low-risk group (p = 0.222), but there was a significant advantage in the middle- and high-risk patients (p = 0.001). After a median follow-up of 45 months, a total of 49 deaths occurred and 50 patients developed disease progressions but remained alive. The 3-year PFS was 83.7% for MDex group, 87.9% for ASCT group, and 65.2% for LDex groups. The 3-year OS was as follows: MDex group 90.6%, ASCT group 94.4%, and LDex group 81.6%. The ASCT group achieved a better PFS than the LDex group (p = 0.003), while the three groups had no significant differences in 3-year OS (p = 0.069). CONCLUSION: All three treatment regimens have achieved good efficacy and survival in the treatment of POEMS syndrome. Compared with melphalan and lenalidomide-based regimens, patients at medium to high risk may benefit more from autologous transplantation. Disclosures No relevant conflicts of interest to declare.

Low Relapse without Excessive Transplant-Related Mortality Following Allogeneic Stem Cell Transplantation in Patients with High Risk Secondary Acute Myeloblastic Leukaemia and Myelodysplastic Syndromes, Long-Term Outcomes in a Single Centre Experience.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4308-4308
Author(s):  
Jean El-cheikh ◽  
Luca Castagna ◽  
Sabine Furst ◽  
Catherine Faucher ◽  
Benjamin Esterni ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Allogenic Stem Cell Transplantation ◽  
Related Mortality

Abstract Abstract 4308 Allogenic stem cell transplantation (Allo-SCT) as a therapy for secondary acute myeloid leukaemia (sAML) and myelodisplastic syndromes (MDS) is the most powerful treatment option. However, (Allo-SCT) is also complicated by a high risk for treatment-related morbidity and mortality. We analysed retrospectively the data of 70 patients transplanted at our institution from June 1995 to december 2008, 44 patients (63%) with sAML and 26 patients (37%) with MDS was treated with (Allo-SCT); median age at diagnosis was 41 years, (15-70), and the median age of 42, 5 years (16-70) at transplantation; The conditioning regimen was myeloablative combining (cyclophosphamide and TBI) in 16 patients (23%) and 54 patients (77%) was with a reduced intensity conditioning (RIC) regimens combining fludarabine, busulfan, and antithymocyte globulin; 11 patients (16%) were infused with bone marrow (BM), 55 patients (79%) peripherical blood stem cells (PBSC), and 4 patients (5%) cord blood cells; in 49 cases (70%) donor was a HLA identical sibling and in 21 (30%) was a matched unrelated donor; 41 patients (59%) carried high risk cytogenetic features, like (7q-, 5q-, > 3 alterations), while was normal in 24 patients (34%), and in 5 patients (7%) was unknown. Disease status at transplantation was as follow: CR in 24 patients (34%), 34 patients (49%) was refractory or in progression after treatment, and 12 patients (17%) was with a stable disease. With a median follow-up of 55 months (3-150), 30 patients (43%) are alive, the overall survival OS at 2 years and 5 years was 48 % and 39% respectively, and after ten years of follow up, OS was 30%, 95%CI [17.8-50.8]. We observed also that 26 % of refractory patients and 54% of patients in CR are alive at five years of transplantation. The probability of progression after transplantation at five and ten years was 31% with 95%CI [20.-46.5]. 2 years and 5 years treatment related mortality (TRM) was 23% and 26% respectively, and no modification at ten year, 95%CI [14.3-37.3]. TRM occurred in 16 patients (23%). Cause of death was; infections in 5 patients (7%), GvHD in 3 patients (4%), GvHD and infection in 3 patients (4%), multi organ failure (MOF) in 5 patients (7%). In multivariate analysis; OS, PFS or TRM, were not influenced by donor type (HLA id sibling vs others), conditioning regimen (RIC vs MAC), and stem cell source (bone marrow vs PBSC). Allogenic stem cell transplantation can be considered as a good option for the treatment of patients with high risk sAML and MDS when compared with the remission rate at five years of the other nonallogeneic SCT therapies. Disclosures: No relevant conflicts of interest to declare.

Effectiveness of Reduced Toxicity Conditioning Regimen with Intravenous Busulfan Plus Pentostatin (BUPENT) in Patients Older Than 50 Years with Advanced Hematologic Malignancies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3331-3331
Author(s):  
Tulio E. Rodriguez ◽  
Mala Parthasarathy ◽  
Scott E. Smith ◽  
David H. Vesole ◽  
Zachary M. Earley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Graft Failure ◽  
Conditioning Regimen ◽  
Advisory Committees ◽  
Reduced Toxicity

Abstract Abstract 3331 Poster Board III-219 Introduction Current data suggests that recipient age above 50 is associated with an inferior outcome after myeloablative allogeneic stem cell transplantation (SCT). Overall survival (OS) of 31%, and transplant related mortality (TRM) of 17% at 100 days have been reported in this population (Ditchkowski, et al 2005; Yanada, et al. 2004). Encouraging results are observed with non-myeloablative conditioning regimens. However, for patients with a high relapse risk, this approach may not be sufficient to achieve long term disease control. In these cases, a reduced toxicity, yet ablative stem cell transplantation (RT-SCT) may give adequate time to the transplanted cells to mature and mount an immune-mediated antitumor response. This study evaluated the outcome after RT-SCT using a conditioning regimen consisting of intravenous busulfan (Bu) and pentostatin (Pent). Methods Consented adult patients up to 70 years with a fully-matched related (MRD) or unrelated donor (MUD) were screened for enrollment. Conditioning consisted of Bu 1.6 mg/kg every 12 hours days -7 to -4, and Pent 4 mg/m2 on day -3 and -2 prior to stem cell infusion on day 0. GVHD prophylaxis was methotrexate 10 mg/m2 on day 1, and 5 mg/m2 on days 3, and 6. Tacrolimus was started on day -2, and then tapered over 1 month after day +100. Characteristics Twenty six patients were analyzed. Male to female ratio was 1:1. Stem cell source was from MRD in 15 patients and MUD in 11. Median age was 62, with 92% of patients being older than 50 years. Indications for treatment were AML (35%), MDS (42%), Refractory CLL (23%), Relapsed NHL (12%), and Philadelphia (+) ALL (4%). All AML patients were high risk either due to poor cytogenetic, transformation, or relapse and only two of them were transplanted in first complete remission. MDS patients were RAEB (36%), secondary MDS (36%), or multilineage dysplasia (18%). Two patients had prior autologous transplants. Results No graft failure was observed. All patients achieved neutrophil (NEU) engraftment. Two patients expired prior to platelet (PLT) engraftment. Median engraftment days for NEU and PLT were 13 days. At a median follow up of 25 months, the OS and progression free survival for the entire group was 40% and 38% respectively. The OS in the MRD group was 58%. TRM at 100 days was seen in one patient (4%) due to veno-occlusive disease (VOD). Limited chronic GVHD was the most common observed toxicity (54%), followed by diarrhea (30%) and mucositis (23%). Mucositis was mainly grade 1 (8%) and grade 2 (8%). No grade 3 mucositis was observed. There was only one case of VOD and one case of acute GVHD. Conclusion To our knowledge, this is the first report of a RT-SCT using BuPent. This study demonstrates the efficacy of the regimen in patients older than 50 years. No graft failure was observed and the regimen related toxicity was acceptable in this high-risk population. The overall survival of 40% at a median follow up of 25 months compares favorably with prior reports of myeloablative allogeneic stem cell transplatation in patients older than 50 years. This regimen provides an exciting opportunity to extend the benefits of allogenic transplant to an older population, and warrants replication with larger controlled trials. Disclosures Rodriguez: Otsuka: Membership on an entity's Board of Directors or advisory committees, Research Funding. Vesole:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Speakers Bureau; Millenium: Speakers Bureau; Centocor Ortho Biotech: Speakers Bureau.

A Novel Sequential Treatment Utilizing CPX-351 As Salvage Chemotherapy Followed by a Reduced Intensity Conditioning Allogeneic Stem-Cell Transplantation for Patients with Refractory Leukemia

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3030-3030
Author(s):  
Usama Gergis ◽  
Gail J. Roboz ◽  
Ellen Ritchie ◽  
Joseph M. Scandura ◽  
Karen-Sue B. Carlson ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Acute Leukemia ◽  
Reduced Intensity Conditioning ◽  
Co Morbidity ◽  
Phase 1B ◽  
Morbidity Index ◽  
Reduced Intensity

Abstract Abstract 3030 Introduction: Allogeneic Hematopoeitic Stem cell Transplantation (HSCT) using standard ablative or reduced intensity conditioning regimens is often ineffective in patients with primary refractory and relapsed acute leukemia. Sequential administration of cytoreductive chemotherapy followed by a Reduced Intensity Conditioning (RIC) regimen may lead to improved results (Schmid et al Blood 2006). CPX-351 is a novel liposomal formulation that encapsulates the combination of cytarabine and daunorubicin in a fixed 5: 1 ratio. In vitro, it selectively concentrates in the marrow compared to other organs. Clinically, CPX-351 is well tolerated, with a favorable extramedullary toxicity profile, making it an appropriate cytoreductive agent prior to conditioning for HSCT. Patients and Methods: In a 3+3 phase I trial, patients with relapsed or primary refractory acute leukemia were treated with escalating doses of CPX-351 starting at 60 mg/m2 on days - 28, -26 and -24 followed by RIC with IV busulfan 3.2 mg/kg/day on days -6 to -3 and fludarabine 30 mg /m2/day on days -6 to -3 (Bu/Flu). GVHD prophylaxis consisted of tacrolimus starting on day -3, at a starting dose of 0.03 mg/kg/24 hours as a continuous infusion and adjusted to achieve a trough level between 10 and 15 ng/ml. and methotrexate 10 mg/m2 IV on days 1, 3, 6 and 11 (Methotrexate dose was reduced to 5 mg/m2 after observing grade 3 mucositis in the first 3 patients). The protocol was amended to include a phase 1B in addition to the above mentioned phase 1A. In phase 1B, patients were treated with escalating doses of CPX-351 starting at 60 mg/m2 on days - 21, -19 and -17 followed by IV Bu/Flu conditioning. Thirty two patients (AML-27, ALL-2, CML in blast crisis-1, high risk MDS-2) have been enrolled to date. Nine patients are in-evaluable due to short follow up (2), sepsis resulting in aborted transplant plans (4), appendicitis (1), early death at day +12 due to sepsis prior to engraftment (1) and donor's unavailability after receiving one dose of CPX-351 (1). Twenty three patients who underwent HSCT are evaluable (AML-19, ALL-2, high risk MDS-2). We calculated the transplant co-morbidity index as well as the prognostic score identified by the CIBMTR in patients with refractory leukemia undergoing HSCT (Duval et al. JCO 2010). The twenty three evaluable patients have a median age of 58 (range 33–72), co- morbidity index 2 (range 0–6) and CIBMTR score 3 (range (2–5). All patients received HLA compatible grafts (MUD-15, MRD-8). Results: Nineteen patients achieved complete hematologic remission by day 30 post transplant. All nineteen patients had adequate donor's engraftment for neutrophils and platelets at a median time of 15 days (range 12–35) and 16.5 days (range 10–90) respectively. Four patients continued to have active disease by day 30. Five more patients had a disease relapse before or shortly after day 100 and one patient had a relapse 22 months post transplant for a total of 10 relapsed patients (43%). Three patients died of acute GI GVHD 2, 6 and 9 months after transplant (all were in remission). One patient died of a pre existing brain tumor progression and one patient died of liver cirrhosis due to iron overload one year after transplant for a total non relapse mortality of 21%. At a median follow up of 6 months, eight patients are alive without evidence of leukemia (35%). Acute GVHD grade II-IV occurred in 8 patients (35%) and was the cause of death in 3 patients. Chronic GVHD occurred in 3 patients (13%). Grade 2 mucosal injury as defined by Bearman toxicity criteria was the most common toxicity developing in 15 patients (65%). Conclusion: The maximum tolerated (MTD) dose of CPX-351 followed by RIC HSCT was not found after a series of 4 treatment cohorts on Arm A and 2 treatment cohorts on arm B. Further dose escalation to define MTD is ongoing in both arms. Remission status is not a prerequisite for a successful outcome in selected patients who otherwise are candidates for transplantation. Disclosures: Off Label Use: CPX is not FDA approved. Feldman:celator: Consultancy.

Graft-Versus-Host Disease after Haploidentical Stem Cell Transplantation in High Risk Haematological Diseases: A 10-Years Evaluation at San Raffaele Scientific Institute

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2498-2498 ◽  
Author(s):  
Maria Teresa Lupo-Stanghellini ◽  
Alessia Orsini ◽  
Lara Crucitti ◽  
Roberto Crocchiolo ◽  
Raffaella Greco ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Mortality Rate ◽  
Stem Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Complete Resolution ◽  
High Dose ◽  
Graft Versus Host ◽  
Nih Consensus Criteria

Abstract Introduction Haematopoietic stem cell transplantation (HSCT) is the only curative option for patients (pts) affected by high-risk haematological diseases (HRHD). However, the availability of a match donor is still an unmet-medical need. Recently alternative donor transplantations have been broadly exploited, reaching results similar to transplants from a well match donor. Anyway, whoever the donor is, the most important complication remains Graft-versus-Host Disease (GvHD). Aim of the study We evaluated incidence, characterization, stratification, treatment, treatment response and outcome at medium and long-term follow-up for both acute (a-) and chronic (c-) GvHD in haploidentical setting. We also evaluated the impact of the NIH consensus criteria on GvHD in a routine clinical application to confirm their feasibility in daily practice and not only in clinical trials use. Methods A population of 257 pts was selected from our Institutional database on the basis of their having an HRHD with indication to allogeneic HSCT and having received a HSCT from an haploidentical family donor without exclusion. HSCT were performed between January 2004 and December 2013 at our Center. No distinction between first HSCT or subsequent one was made, all consecutive haploidentical HSCT were captured. Results Time of median follow-up was 10 months; 1-year overall-survival (OS) was 46%, with better outcome for pts transplanted in complete remission (p 0.0001) confirming disease status as the leading factor for overall outcome. Transplant related mortality was estimated to be 30% at 1 year and the leading cause of death was infections. The 6-months a-GvHD incidence was 45% (119/257) - median day of presentation 21 post HSCT (range 8-89). Late-onset a-GvHD was documented in 15 pts. Grade I GvHD was documented in 33 pts (27.7%), grade II in 44 (37%), grade III-IV in 36 (30.3%) – 6 not evaluable. Skin was the most frequently involved organ (77.3%), both as single manifestation or combined. One-hundred and five pts received a first line therapy based on high-dose prednisone (2mg/Kg) and 37/105 completely abrogated the a-GvHD. At a 3-months evaluation 46% of affected pts showed complete resolution of a-GvHD, while the mortality rate was 29%. C-GvHD affected 69/257 pts and 1-year risk of onset was 25% - median day of presentation was 139 post HSCT (range 40-809) and 36/69 pts were off immunosuppressive therapy (52.3%) at presentation. According to onset presentation 53.7% were de novo, 24.6% progressive and 18.8% quiescent GvHD. Forty-one pts (59.5%) presented at declaration with overlap features. The most frequent involved organ was skin (grade I to III), as reported in 53 pts (76.8%). Skin lesions were usually accompanied with mouth lesions (35 pts – 50.7%), liver (23 pts – 33.3%) or eyes (27 pts – 39.1%) dysfunctions. The median number of involved organs was 3 (range 1-7). Mild c-GvHD was diagnosed in 10 pts (14.5%), who received topical therapy. Fifty-nine pts – diagnosed with moderate (32, 46.4%) or severe (27, 39.1%) - received a systemic treatment for c-GvHD: prednisone 1 mg/Kg alone or 0,5 mg/kg plus mTOR- or calcineurin-inhibitor for pts that were not likely to tolerate high dose steroid due to comorbidity (namely active infections, diabetes, cardiovascular diseases). At a 12-months evaluation the overall response was 48% (complete resolution 25%, partial resolution 23%), while the mortality rate was 36%. The Landmark analysis of OS at 3 months after HSCT shows that a-GvHD affected pts had a worse outcome (p= 0,068), on the contrary the Landmark analysis of OS at 18 months shows that c-GvHD did not associate with a worse outcome (p ns) but the follow up is still short. Confirming previous reports, overlap c-GvHD was related to worse survival in comparison with classic c-GvHD (p 0.0098). Conclusion Haploidentical HSCT is a valid and feasible option for pts in need of a transplant. GvHD is manageable after haploidentical HSCT, as in full matched setting. Better knowledge and insight in a/c-GvHD are providing advance in improving pts outcome. The NIH-consensus criteria are manageable in daily clinical practice and able to translate in a tailored approach to GvHD with benefit on general outcome. Further advance in the development of specific biomarkers for GvHD will provide additional crucial information for management, diagnosis and prognostication in GvHD. Figure 1 Figure 1. Disclosures Bonini: MolMed S.p.A.: Consultancy. Bordignon:MolMed: Employment.

Long-term health status of high-risk neuroblastoma survivors treated with high-dose chemotherapy and hematopoietic stem cell transplantation.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 10054-10054 ◽  
Author(s):  
Sandrine Haghiri ◽  
Chiraz Fayech ◽  
Christelle Dufour ◽  
Claudia Pasqualini ◽  
Stephanie Bolle ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Second Cancers

10054 Background: Current treatment strategies including high-dose chemotherapy with stem cell transplantation rescue (HDC-SCT) have improved 5-year event-free survival for high-risk neuroblastoma (HRNB) patients, but with an increased risk of late treatment-related toxicities. Methods: Between 1980 and 2012, 439 children were treated for HRNB with HDC-SCT in Gustave Roussy (GR), among which 145 were alive and disease-free at 5-year post-SCT. Long-term health data have been collected for those 145 patients, prospectively within the long-term follow-up clinic in GR or retrospectively from pediatric consultations. Results: With a median follow-up post-SCT of 15 years (range 5-34), we observed 6 late relapses, 11 second cancers (including 3 papillary thyroid carcinomas; median delay = 20 years post-SCT [18-22]) and 9 deaths. Event-free and overall survival at 20-year post-SCT were 82% (95%CI = 70–90) and 89% (95%CI = 78–95), respectively. A second health event was observed in 135 patients (median = 3/patient), including 103 patients with at least 1 severe event (median = 1/patient). Cumulative incidence at 15-year post-SCT for second cancers is 4%, cardiac diseases 8%, thyroid 11%, renal 7%, hepatic focal nodular hyperplasia 14%, dental mal-development 70%, and severe hearing loss 20%. Height-for-age z-score was ≤-2 for 30 patients (21%) and ≤-3 for 12 patients (8%). After Busulfan-Melphalan conditioning regimen, 40/43 females and 33/35 males had a gonadal insufficiency. Conclusions: Long-term consequences of HRNB treatment including HDC are frequent and disabling, mainly due to hearing loss and gonadal insufficiency.

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