Long-Term Follow-Up of Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) with Fludarabine and Melphalan (FM) Reduced Intensity Conditioning (RIC) for High-Risk AML/MDS.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 838-838
Author(s):  
B. Oran ◽  
R. Saliba ◽  
S. Giralt ◽  
D. Couriel ◽  
A. Carrasco-Yalan ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
High Risk ◽  
Disease Progression ◽  
Disease Status ◽  
Independent Effect ◽  
Donor Type

Abstract RIC with FM has extended the use of HSCT to patients otherwise not eligible for this treatment. Longer follow-up and larger number of patients now allow for more robust evaluation of risk factors and outcomes. Herein are the results of such an evaluation. Patients and Methods: We evaluated outcomes of 112 patients with high-risk AML/MDS treated from August 1996 to December 2003 with FM (fludarabine 100–180 mg/m2 and melphalan 100–180 mg/m2) and unmanipulated HSCT. Eligibility included age >54 yrs. or comorbidity precluding an ablative preparative regimen. Disease status at HSCT was relapsed/refractory (n=43, 38.4%), primary induction failure (n=32, 28.6%), untreated (n=7, 6.3%) or complete remission (CR, n=30, 26.8). Cytogenetic risk was intermediate (n=59, 53%), high (n=47, 42%), low (n=3, 2.5%) or unknown (n=3, 2.5%). Donors were HLA matched related (MRD; n=59) or unrelated (UD; n=53). GVHD prophylaxis was tacrolimus based in all but one patient. Anti-thymocyte-globulin was added in 31 UD HSCT. Stem cell sources were bone marrow (n=56) or peripheral blood (n=57). Median age was 55 (range 22–74). Evaluated were the following variables and their influence on disease progression and overall survival: - age, donor type, duration of first CR, disease status at transplant (categorized as CR, No CR with (NoCR/CB) and without circulating blasts (NoCR/NoCB)), cytogenetics, acute and chronic GVHD (time dependent variables), and blood counts on day 30 (lymphocytes, monocytes and platelets). We used a Cox’s regression analysis. Results: Median time of follow up among survivors (n=43) was 28.4 mo (3.3–88.9). CR rate at day 30 post transplant was 87% (n=97), 8 patients died early and 7 did not respond. 25 (26%) of 97 patients progressed after day 30. All but 3 patients relapsed within the first year post HSCT, and only one relapsed more than 2 years after HSCT. In a landmark analysis, disease status at transplant was the only significant risk factor for progression among these 97 patients (HR of 3.7 for the NoCR/CB group compared to the CR group). 69 of 112 patients died with a median survival of 4.6 mo. Seven deaths (10% of all deaths) were observed more than 2 yrs. after HSCT, due to GVHD (n=3), infection (n=2), relapse (n=1) and unknown causes (n=1). Two-year OS and PFS was 44% and 69% respectively. Disease status at HSCT and grade II-IV aGVHD were the only significant predictors of OS on univariate and multivariate analysis. Blood counts on day 30 were associated with disease status at transplant, donor type and aGVHD. Their independent effect on outcome could not be evaluated given sample size. Conclusion: A significant portion of older patients with high-risk AML/MDS may achieve long-term PFS, but early relapses are the major cause of treatment failure in this context. Prognostic factors for event-free and overall survival Variables Multivariate analysis for disease progression CB=circulating blasts Disease status n Events (n) HR 95% CI p 2-yr PFS CR 30 6 1.0 57% (39–72) NoCR/NoCB 41 7 1.1 0.4–3.2 0.9 46% (30–60) NoCR/CB 26 12 3.7 1.4–9.8 0.001 22% (9–38) Multivariate analysis for overall survival (OS) Disease status HR 95% CI p 2-yr OS CR 30 12 1.0 66% (48–80) NoCR/NoCB 49 29 1.8 0.9–3.5 0.06 40% (26–53) NoCR/CB 34 28 2.8 1.4–3.5 0.002 23% (11–37) gd II-IV aGVHD 2.8 1.8–4.6 <0.001

Allogeneic Stem Cell Transplantation (allo-SCT) for Chronic Lymphocytic Leukemia: a Long Term Analysis From the Societe Francaise De Greffe De Moelle Et De Therapie Cellulaire (SFGM-TC).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 201-201
Author(s):  
Mohamad Mohty ◽  
Jean-Paul Vernant ◽  
Ibrahim Yakoub-Agha ◽  
Didier Blaise ◽  
Gérard Socié ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Chronic Lymphocytic Leukemia ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Acute Gvhd ◽  
Disease Status ◽  
Lymphocytic Leukemia

Abstract Abstract 201 Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with a heterogeneous natural history. While some patients never require treatment or can be managed effectively with conventional chemotherapy, others experience early disease progression and death. Allo-SCT is increasingly considered as a therapeutic option for younger patients with poor-risk CLL. This multicenter retrospective analysis assessed the long term outcome of 160 CLL patients who received allo-SCT between 1987 and 2005, and were reported to the SFGM-TC registry. This series included 127 males (79%) and 33 females (20.6%) with a median age at CLL diagnosis of 45.5 (range, 24.4–65.1) y. The median age at time of allo-SCT was 50.9 (range, 29.8–68.3) y. Before allo-SCT, 26 patients (16.3%) received previous stem cell transplantation in the course of their disease. Patients received either a standard myeloablative conditioning regimen (n=58; 38%; Cy-TBI in 90% of cases) or a so-called reduced-intensity conditioning. A matched-related donor was used in 142 cases (89%) and PBSCs were used as source of stem cells in 92 cases (57.5%). At time of allo-SCT, only 10 patients (6.3%) were in CR1, 17 in CR2 and CR3 (10.6%), 27 in first PR (16.9%) and 106 (66.2%) in more advanced phases, including 46 patients (28.8%) in progressive disease. With a median follow-up of 60 (range, 1.6–208) months for surviving patients, 96% of patients engrafted (ANC>500/μL) at a median of 18 (range, 1–41) days after allo-SCT. 71 patients (44.4%) experienced grade 2–4 acute GVHD, including 28 cases (17.5%) of grade 3–4 acute GVHD. 73 patients (56.2%) experienced some form of chronic GVHD. At time of last follow-up, 70 patients (43.8%) were still alive, of whom 24 (34%) were in continuous CR. Disease progression accounted for 24 deaths, while transplant-related causes (infections, n=23; GVHD, n=13; MOF, n=12; other causes, n=18) were observed in 66 cases, for a TRM rate of 41%. The KM estimates of disease-free survival (DFS) at 2, 5, and 10 years after allo-SCT were 44.3%, 39.6%, and 30.5%, respectively. Estimates of overall survival (OS) were 54.4%, 46.2%, and 35.8.1%, respectively. In a Cox multivariate analysis for OS (including demographic features, transplant and donor types, and disease status at time of allo-SCT), disease status at time of allo-SCT (CR or PR) was the most significant parameter associated with improved OS (RR=0.56; 95%CI, 0.36–0.89). We conclude that allo-SCT has the potential to induce long-term disease control and overall survival in patients with high risk or advanced CLL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals High Rate of Long Term Complete Remission for Patients with Chronic Lymphocytic Leukemia (CLL) Who Relapse after Allogeneic Stem Cell Transplantation and Receive Salvage with Donor Lymphocyte Infusions (DLI)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5860-5860
Author(s):  
Alan P Skarbnik ◽  
Mary E DiLorenzo ◽  
Tracy Andrews ◽  
Phyllis McKiernan ◽  
Scott D. Rowley ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Board Of Directors ◽  
Research Funding ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Disease Status ◽  
Advisory Committees

Abstract Background: Allogeneic stem cell transplantation (SCT) remains the only curative option for CLL, in part due to allogeneic graft-vs-leukemia effect (GVL), which can lead to complete suppression of the CLL clone (Schetelig et al, JCO 2003). Management of post-SCT relapse remains challenging, and DLI has been successfully used as salvage, due to its potential to induce GVL (Delgado et al, Blood 2009). We evaluated outcomes of SCT for patients (pts) with a diagnosis of CLL transplanted at our center. Methods: 36 consecutive pts transplanted between 2004 and 2015 were reviewed. Kaplan Meier survival curves were produced to examine overall survival (OS), time to progression (TTP) and post-DLI survival. Univariate Cox Proportionate hazard models were also estimated to assess the impact of pt characteristics on the risk of survival and progression. Bivariate frequencies with Fisher exact tests, correlation analysis, and independent samples t-tests were performed to test associations across outcomes. Results: Sample was 72% male. Median age at time of SCT was 57 yo (range 42-74). Pts had a median time of 70 months (mos) between diagnosis (Dx) of CLL and SCT. Median follow-up post-SCT was 32 mos (range 1-118). Of the 30 pts with known disease status at the time of SCT, 16.7% were in complete remission (CR), 20% had stable disease (SD), 50% were in partial remission (PR) and 13.3% had progressive disease (PD). Median number of lines of therapy pre-SCT was 3 (range 1-8). Thirteen pts (36%) were refractory to their first line of therapy. 10 pts (27.8%) had del(17p), 11 pts (30.6%) had del(11q) and 8 pts (22.2%) had complex cytogenetics. Most patients (72%) received pre-SCT conditioning with FCR (Khouri et al, Exp Hematol 2004). 16 pts (44.4%) received rATG as part of their conditioning regimen. Graft-vs-host disease (GVHD) prophylaxis consisted of methotrexate and tacrolimus. 20 (55.6%) pts had acute GVHD and 19 (52.8%) had chronic GVHD. 5 (13.8%) pts had grade 3/4 acute GVHD and 1 (2.7%) had extensive chronic GVHD. When comparing pts who received SCT from unrelated donors (MUD, 24 pts) vs sibling donors (sib, 10 pts) there were no differences in rates of GVHD, disease progression or overall survival. Twenty-seven pts (75%) were in CR at first disease evaluation after SCT (CR conversion rate of 58.3%) and 2 pts (5.5%) had PD. On follow-up, another 15 pts (41.7%) presented PD. Median TTP was 14 months, with only 3 pts relapsing after 2 years from SCT. Eight pts who had PD and one patient who had a PR post-SCT received short-term anti-CLL therapy for disease debulking, followed by DLI. Six (66.6%) out of the 9 pts who received DLI achieved CR and are currently alive and in CR. Median follow-up post-DLI was 43 months and median duration of response to DLI was 47 mos (range 6-85 mos). Ultimately, 13 (36.1%) pts died, 8 (22.2%) were lost to follow-up, and 15 (41.7%) were alive at last contact. Disease progression was the most common cause of death (5 pts, 13.9%). Transplant-related mortality (TRM) was 13.9% (3 deaths due to infection, 2 deaths due to chronic GVHD). Only 2 deaths (5.5%) occurred during the first 100 days post-SCT, both due to infection. No deaths occurred due to acute GVHD. Median OS was 84 months. PFS (not accounting for pts who relapsed post-SCT but achieved CR with DLI) was 58% in the first year and 25% at five years. The median PFS was 19 months. Univariate and multivariate analysis of pre-SCT pt characteristics (age, time from Dx to SCT, number of therapies, stage, presence of adenopathy, MUD vs sib donor, cytogenetic abnormalities, ABO mismatch, disease status at SCT) did not show any statistically significant correlation with OS, PFS or GVHD rates. Conclusion: SCT remains the only curative option for CLL. Our experience shows that pts may achieve long-term survival with this approach. TRM was low (13.8%) and rates of acute and chronic GVHD were compatible with previous reports (Sorror et al, JCO 2005; Dreger et al, Blood 2010). Type of donor (MUD vs sib) did not impact outcomes, suggesting that patients without a matched sibling should not be denied transplantation if a MUD is available. Although 47% of the patients eventually progressed after transplantation, 66% of patients who received DLI for salvage were able to achieve CR and remain progression-free for a prolonged period of time, underlining the importance of the GVL effect. Most relapses occurred within the first 2 years post SCT and late relapses were rare. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures Skarbnik: Gilead Sciences: Speakers Bureau; Seattle Genetics: Speakers Bureau; Genentech: Speakers Bureau; Abbvie: Consultancy; Pharmacyclics: Consultancy. Vesole:Celgene: Speakers Bureau; Takeda: Speakers Bureau; Janssen: Speakers Bureau; Amgen: Speakers Bureau; Novartis: Speakers Bureau. Goy:Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Writing support, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Infinity: Consultancy, Membership on an entity's Board of Directors or advisory committees; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Feldman:Pharmacyclics: Speakers Bureau; Celgene: Speakers Bureau; Seattle Genetics: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Leslie:Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau. Leslie:Seattle Genetics: Speakers Bureau; Celgene: Speakers Bureau.

Thirty-Five Year Follow-up Analysis of Follicular Lymphoma Patients Treated through the Nebraska Lymphoma Study Group: Prognostic Factor Analysis and Outcomes

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 7-8
Author(s):  
Amulya Yellala ◽  
Elizabeth R. Lyden ◽  
Heather Nutsch ◽  
Avyakta Kallam ◽  
Kai Fu ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Follicular Lymphoma ◽  
Treatment Regimen ◽  
Research Funding ◽  
Study Group ◽  
Secondary Malignancies ◽  
Lymphoma Study Group

Background Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL) and most common of the clinically indolent NHLs. Although often considered an incurable disease, overall survival has increased significantly with refinement in diagnostic techniques and the addition of rituximab. The course of FL is quite variable and presence of symptoms, organ dysfunction, cytopenias, aggressiveness of tumor are all taken into consideration when deciding individual treatment. In this study, we evaluated a large patient cohort with FL treated over a 35 year period for progression free survival (PFS), overall survival (OS) based on FLIPI score, tumor grade, and treatment regimen and also looked at causes of late failures. Methods We evaluated 1037 patients (pts) from the Nebraska Lymphoma Study Group that were diagnosed with FL between the years of 1983-2020. Descriptive statistics were stratified according to age, histological subtype, treatment regimen, FLIPI category, presence and type of secondary malignancy. PFS was calculated from the time of diagnosis to progression or death and OS was the time from diagnosis to death from any cause. PFS and OS were plotted as Kaplan-Meier curves with statistically significant p<0.05. Results The median age at diagnosis and treatment was 61 years (yrs, range 17-91). A total of 9.1% were characterized as FLIPI high risk, 37.8% intermediate risk, and 33.6% low risk, 19.5% unavailable. Among the histological grade, 23.1% had FL- grade 1, 30.2% FL-2, 27.3% FL-3A, 2.5 % FL-3B and 16.9 % Composite Lymphoma. Anthracycline + rituximab was given in 24.5% of pts, whereas 43.8% of pts received an anthracycline based regimen without rituximab, 9.8% received rituximab without an anthracycline and 10.6% received neither of these agents. 6.75% (70 pts) were later found to have secondary malignancies of which 11 pts had myelodysplastic syndrome, 10 pts had acute leukemia and 9 pts had lung cancer. With a median follow up of 9.2 yrs and a maximum of 36 yrs, 29.7% (308 pts) had not relapsed. The median PFS across all groups was 4.6 yrs (Fig 1) and OS was 12.1 yrs. Median OS was significantly longer in patients that received rituximab at 16.1 yrs as compared to patients that did not receive rituximab at 9.89 yrs (Fig 2). PFS was 8.6 yrs, 3.6 yrs and 2.1 yrs and OS was 15.1 yrs, 11.7 yrs and 4.9 yrs in FLIPI low, intermediate and high risk groups respectively (p=<0.001) (Fig 3), suggesting that survival was influenced by FLIPI score. Median PFS in FL-3B and FL-3A was 9.2 yrs and 5.2 yrs respectively which is longer than 4.7 yrs and 4.2 yrs for FL-1 and FL-2 (p=0.24). OS in FL-3A and FL-3B subgroups was 10.8 yrs while it was 11.6 yrs and 14.3 yrs in FL-2 and FL-1 (P=0.081). PFS is significantly longer at 10.6 yrs in pts treated with both anthracycline and rituximab containing regimen as compared to 5.3 yrs in pts treated with rituximab alone and 3.05 yrs in pts that had only anthracycline based regimen (p=<0.001) (Fig 4). The median OS also was significantly higher in the combination regimen group at 18.8 yrs as compared to 11.3 yrs in rituximab only group and 9 yrs in anthracycline based regimen group (p=<0.001). When pts with FL-3A and FL-3B were grouped together and stratified according to treatment regimen, the group that received anthracycline and rituximab combination has highest PFS and OS at 13.3 yrs and 18.8 yrs (p<0.001). when pts with FL-3A were analyzed separately and stratified by treatment regimen, the results of PFS and OS were similar and statistically significant. However, of the 24 pts in FL-3B group, analysis revealed that PFS and OS was longer in anthracycline based regimen only group, however results were not statistically significant. Among the pts that relapsed/died after 10 years (n=190), the cause of death was relapsed lymphoma in 13.7%, unknown in 55.8%, secondary malignancies in 4.2%, treatment related in 2.6% and not related to disease in 23.7%. A total of 278 pts survived > 10 yrs, and of these pts, 119 (30%) had not relapsed at the last follow up. Conclusion The addition of rituximab to standard anthracycline based chemotherapy has resulted in significant improvements in the PFS and OS rates of FL. These results also support the prognostic value of the FLIPI in patients treated in the rituximab era. Late relapses after 10 yrs from disease can occur, but 11.5% of patients had not relapsed with long term follow up. Secondary malignancies are also an important consideration in the long term survivors. Disclosures Lunning: Acrotech: Consultancy; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding; Beigene: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Bristol Meyers Squibb: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Legend: Consultancy; Verastem: Consultancy, Honoraria; ADC Therapeutics: Consultancy. Armitage:Trovagene/Cardiff Oncology: Membership on an entity's Board of Directors or advisory committees; Samus Therapeutics: Consultancy; Ascentage: Consultancy. Vose:Bristol-Myers Squibb: Research Funding; Karyopharm Therapeutics: Consultancy, Honoraria; Seattle Genetics: Research Funding; Allogene: Honoraria; AstraZeneca: Consultancy, Honoraria, Research Funding; Kite, a Gilead Company: Honoraria, Research Funding; Wugen: Honoraria; Novartis: Research Funding; Celgene: Honoraria; Incyte: Research Funding; Roche/Genetech: Consultancy, Honoraria, Other; Verastem: Consultancy, Honoraria; Miltenyi Biotec: Honoraria; Loxo: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Epizyme: Honoraria, Research Funding; AbbVie: Consultancy, Honoraria.

Long Term Follow-Up of 4-Hydroperoxycyclophosphamide Purged Autologous Bone Marrow Transplantation in Non-Hodgkin’s Lymphoma Patients with High Risk of Bone Marrow Involvement.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5234-5234
Author(s):  
Elise A. Chong ◽  
Charalambos Andreadis ◽  
Stephen J. Schuster ◽  
Selina M. Luger ◽  
David L. Porter ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
High Risk ◽  
B Cell ◽  
Tumor Cells ◽  
Platelet Transfusion ◽  
High Dose ◽  
Free Survival

Abstract Introduction: High-dose chemotherapy and autologous stem cell transplant (ASCT) can result in long term survival for patients with advanced non-Hodgkin’s lymphoma (NHL) but relapse remains a common cause of treatment failure. Bone marrow (BM) involvement is common in NHL and there is controversy over whether or not reinfusion of BM stem cells contaminated by clonogenic tumor cells is a major cause of relapse following ASCT. Bone marrow purging can reduce the number of tumor cells in vitro, but the impact on relapse and disease free survival (DFS) remains unknown. Methods: Between 1990 and 1993, 20 pts with poor prognosis NHL (B-symptoms, high LDH, bulky adenopathy, stage III or IV, or relapsed disease) at high risk for BM involvement underwent 4-hydroperoxycyclophosphamide (4-hc) purged BM transplantation. Thirteen pts had low grade B-cell NHL, 6 had an intermediate grade B-cell NHL with a small B-cell component, and 1 had T-lymphoblastic lymphoma. Seven of 20 pts had received ≥3 prior chemotherapeutic regimens. Three pts underwent transplantation in first complete remission and 17 pts were in chemotherapy-responsive relapse. At diagnosis, 11 of 20 pts had documented BM involvement, and at ASCT, 6 of 20 pts had BM involvement (all < 5% involvement at BM harvest). Eighteen pts (90%) received 4-hc purged autologous BM, and 2 pts (10%) received 4-hc purged autologous BM and peripheral stem cell support. High dose regimens included Cytoxan/TBI (85%), BCV(10%), and Melphalan/TBI (5%). The median age was 45 yrs (range: 20–57 yrs). The median nucleated cell count of 4-hc marrow that was reinfused was 2.4 × 108 /kg (range: 0.87–5.5). The median time to granulocyte recovery was 26 days (range: 14–59). Two pts died at days 31 and 35 without achieving platelet transfusion independence. In the remaining 18 pts, the last platelet transfusion was given at a median of 29 days post-marrow infusion (range 18–149), and the median in-patient hospital days was 27 (range: 16–82 days). Results: There were 2 deaths (fungal infection and CNS relapse) during ASCT. One pt died in CR after developing secondary AML 5.34 yrs after ASCT. Post-ASCT, 18 of 20 pts achieved CR (including 1 pt who had no evidence of disease at autopsy), 1 pt had a PR, and 1 pt died during BMT and was not evaluable for response. Median follow-up for the group was 8.2 yrs (range: 0.1–12.4 yrs). At last follow-up, 9 pts remain in CR (1 died of AML in CR), 5 pts had relapsed and remain alive, and 5 pts died of progressive disease. Median follow-up for survivors was 11.1 yrs (range: 5.2–12.4 yrs). 65% of pts remain alive at last follow-up. The median EFS was 9.4 yrs (range: 0.1–12.4 yrs). Those who achieved a CR post-ASCT had a median DFS of 10.6 yrs (range: 1.1–12.4 yrs). At 8.2 yrs, 4/6 pts with involved BM at the time of harvest had relapsed or died compared to 7/14 pts with negative BM which is not significantly different. Conclusion: ASCT using 4-hc BM purging is feasible and can result in long term relapse free survival, even for pts with subtypes of NHL at high risk for BM involvement. Whether 4-hc BM purging is equivalent or superior to immunologic approaches to stem cell processing remains to be determined.

Results of T Cell Depleted (TCD) Myeloablative Hematopoietic Stem Cell Transplants (HSCT) in Patients with Hematologic Malignancies ≥ 55 yrs of Age.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3660-3660
Author(s):  
Ann A. Jakubowski ◽  
Esperanza B. Papadopoulos ◽  
Hugo R. Castro-Malaspina ◽  
Katharine Hsu ◽  
Miguel-Angel Perales ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Hematopoietic Stem Cell ◽  
High Risk Patient ◽  
Disease Status ◽  
Unrelated Donor ◽  
Hematopoietic Stem ◽  
Conditioning Regimens ◽  
Good Risk

Abstract Allogeneic HSCT remains the only curative therapy for many patients(pts) with hematologic diseases. Studies have suggested that older pts experience greater toxicity from the intensive chemo-radiotherapy used in myeloablative conditioning regimens. As a consequence, many older pts are now offered non-myeloablative transplants (NMAT) for malignant conditions where a graft vs. tumor effect (GvT) is expected to provide the antitumor effect in place of the chemo-radiotherapy. Unfortunately, graft vs. host disease (GvHD) remains a common occurrence after conventional transplants, occurring more frequently in older pts and unrelated donor transplant recipients, resulting in significant morbidity and mortality. Furthermore, the efficacy of NMAT is limited by the disease status at time of transplant and by the susceptibility of the hematologic disease to a GvT effect. TCD of hematopoietic stem cell grafts offers an alternative to older pts, in particular those requiring unrelated donor transplants (URD), with the advantage of a reduced incidence of GvHD. From 1995–2005, 57 patients ≥55 yrs received myeloablative TCD transplants at our institution. The median age was 58.2 (range 55–69.2) yrs. Stem cell sources were TCD bone marrow, PBSC or both. Thirty-seven received transplants from related donors (RD), including two mismatched, and 20 received transplants from unrelated donors (URD), 9 of whom were mismatched. In addition to their advanced age, many of these pts were considered high risk based on the status of disease, HLA mismatch, and history of previous therapy. Twenty-three pts were considered “good risk” by disease status (CML-CP1, AML-CR1, CR2) and 34 pts were considered poor risk (&gt;CML-CP1, &gt;AML CR2, MDS, NHL, &gt;ALL CR1, ABL.) BM was TCD by soybean agglutination followed by sheep red blood cell rosetting (E), and PBSCs by CD34+ selection and E-rosetting. Conditioning regimens included total body irradiation (TBI) in addition to thiotepa and cyclophosphamide, or thiotepa and fludarabine. The non-TBI preparative regimen consisted of busulphan, melphalan and fludarabine. Anti-thymocyte globulin was used as rejection prophylaxis for all TCD transplants until 2001 when it was eliminated from the TBI containing regimen for matched RD transplants. A total of 25 pts (15 matched RD and 10 URD, 6 of whom were mismatched) are alive following TCD transplants with a median follow up of 24 mos. for RDs and 12 for URDs. Of the survivors, 2/10 URD and 14/15 RD recipients received TBI containing regimens based on the triage system at our center. Three pts with CML-CP1, one with CML-acc and one with AML-CR1 showed evidence of minimal residual disease, received donor leukocyte infusions and subsequently achieved longterm continued CR. The incidence of post-transplant GvHD was low despite the high number of mismatched URD transplants - 1 Grade IV (RD), 2 Grade 3 and 1 Grade 1 (URD). The 100 day mortality was 15%. Overall and current disease free survival for ‘good risk’ patients based on disease status is 58% for RD and 60% for URD. Although longer follow up is necessary to confirm these results, the promising DFS rates in association with a low incidence of GvHD in this older and relatively high risk patient population support further investigation of myeloablative TCD HSCT in these patients.

Long-Term Follow-Up of Allogeneic Stem Cell Transplantation (SCT) with Reduced Intensity Conditioning (RIC) for Patients (pts) with Chronic Myeloid Leukemia (CML).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2898-2898
Author(s):  
Partow Kebriaei ◽  
Michelle Detry ◽  
Antonio Carrasco-Yalan ◽  
Athanasios Anagnostopoulos ◽  
Daniel Couriel ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Acute Gvhd ◽  
Advanced Disease ◽  
Chronic Phase ◽  
Disease Stage ◽  
Disease Group ◽  
Blast Phase

Abstract Allogeneic SCT remains an effective strategy for inducing durable remission in CML. RIC regimens are less myelosuppressive, but adequately immunosuppressive, allowing for engraftment with acceptable treatment-related mortality (TRM) in older pts who otherwise would not be candidates for SCT. The long-term antitumor effect of this approach is not well-established. This is relevant in CML, since many pts present for SCT with advanced disease after failing tyrosine kinase inhibitors (TKI). Patients, Methods: We evaluated outcomes of 64 CML pts (40 M/24 F) with median age 52 yrs (range 18–72) treated from June 1996 to April 2005 with FAI (fludarabine 120 mg/m2, Ara-C 8 gm/m2, idarubicin 36 mg/m2), FM140 (fludarabine 120 mg/m2, melphalan 140 mg/m2 +/− Ara-C 2 gm/m2) or FM180 (fludarabine 120 mg/m2, melphalan 180 mg/m2) and unmanipulated stem cells. Disease stage at time of study entry was first chronic (n=13), second chronic (n=17), accelerated (n=29), or blast phase (n=5), with median time from diagnosis to SCT of 2.6 yrs (range 0.5–20.3). Stem cell source was bone marrow (n=38) or peripheral blood (n=26), and donor type was matched related (n=30), 1 Ag mismatched related (n=4), or matched unrelated (n=30). Graft vs. host disease (GVHD) prophylaxis consisted of tacrolimus and mini-dose methotrexate in all but 6 pts (CSA-based). Anti-thymocyte-globulin was added to all pts other than matched related. Maintenance therapy with TKIs following SCT was not used. Multivariate analysis was done using Cox proportional hazards regression. Results: 22 pts were alive at a median follow up of 7 yrs from SCT (range 0.8–9.8). OS and PFS were 48% and 30%, respectively, at 2 yrs, and 33% and 30%, respectively, at 5 yrs. The cumulative incidence of acute GVHD grades II–IV and III–IV were 31% and 14%, respectively, and chronic GVHD was 32% (22% for extensive). TRM at 100 days, 1-, 2-, and 5- yrs were 2%, 14%, 20%, and 33%, respectively. There was no association between pt age, donor source, preparative regimen, or time to SCT and TRM. Disease recurrence accounted for 12 of 42 deaths. There were 3 cases of graft rejection, with 1 death from graft rejection. Only disease stage at time of SCT was significantly predictive in multivariate analysis for both OS and PFS. Pts with advanced disease had worse OS (HR 2.36, 95%CI 1.25–4.46, p=0.008, see figure) and PFS (HR 1.91, 95%CI 1.05–3.49, p=0.035) than pts in chronic phase. In multivariate for PFS, pts who developed grade I or II acute GVHD were less likely to progress compared to pts who did not develop any GVHD: grade I (HR 0.324, 95%CI 0.13–0.84, p=0.027) and grade II (HR 0.286, 95%CI 0.11–0.78, p=0.014). Conclusion: RIC SCT provides adequate disease control in chronic phase CML pts. The development of some GVHD is protective in this setting. TRM rates are acceptable but continue to increase over time. Alternative treatment strategies need to be explored in pts with accelerated or blast phase disease. Results may be improved with addition of TKI therapy post SCT. Survival by Disease Group Survival by Disease Group

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.

Higher Incidence and Risk of Developing Second Solid Cancers (SSC) after Haematopoetic Stem Cell Transplantation (HSCT) As Compared to General Population

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4610-4610
Author(s):  
Samar Kulkarni ◽  
John Murray ◽  
Charlotte Smith ◽  
Stephanie Cleaver ◽  
Michael Dennis ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Stem Cell ◽  
General Population ◽  
Board Of Directors ◽  
Primary Site ◽  
Single Centre ◽  
Advisory Committees

Abstract Introduction: As the number of long-term survivors following HSCT is increasing, the long-term risks and associated morbidity has become important component of survivorship program. The known risk factors for developing cancer include use of chemotherapy agents, radiation exposure, immune dysfunction, previous malignancy in addition to other factors and as HSCT process involves all these factors, this single centre retrospective analysis was undertaken to evaluate the risk of developing SSC in the patients receiving transplant. Methods: From February 1982 to February 2016, 2231 patients received 2495 transplants (median age: 46yr., range: 14-76 yr.; M: 1586, F: 909) for haematological malignancies (Leuk: 744, lymphoma:767, myeloma:848, solid tumours/other:136). Donor was allogeneic (n=744) or autologous (n=1751) and conditioning was with (n=614) or without TBI (n=1881). Donor was sibling (n=375), matched unrelated (n=355), haploidentical relative (n=3) or umbilical cord blood (n=11). Source of stem cell was marrow (n=367), PBSC (n=2086), both (n=31) or cord blood (n=11). GVH prophylaxis included Campath or ATG in 369 cases. Of all the patients 1985 received single transplant, 231 had two, 13 had 3 and 2 had 4 HSCT procedures. Data was analysed as of 15/04/2016 using competing risk model with death as the competing event. Comparison of incidence to general population was performed by computing standardized incidence rates (SIR). Patients with second haematological malignancy were not included in this analysis. Results: Median follow-up was 5.3 years (range: 0-32 years). Patient follow-up was more than 10 years in 467 cases (19%), between 5 to 10 years in 430 (17%), 2 to 5 years in 607 (24%) and less than 1 year in 997 cases (40%). 36% patients were followed-up for more than 5 years. Second solid cancers developed in 116 patients with the incidence of 1% at 5yr (95% CI: 0.5-2.6), 3% at 10 yr (95% CI: 1.6-5.3), 6% at 15yr (95%CI: 3.6-8.8) and 10% (95% CI: 5.9-15.5) at 20 years. Median time to develop SSC from date of HSCT was 11 yr (range: 0.4-28.1 yr). Primary site for SSC included skin (n=37), breast (n=22), GI (n=15), GU (n=16), H&N (n=10), lung (n=6), CNS (n=4), Endocrine (n=4) & HPB (n=2). There was no difference with type of transplant i.e. auto or allograft. Autograft and allograft groups were analysed separately. In univariate analysis, allograft group showed higher cumulative incidence of SSC with use of PBSC (p<0.0001), campath/ATG (p=0.0002), donor other than sibling (P=0.0004), RIC (p<0.0001), non-TBI conditioning (p=0.007), older age at transplant (0.008), development of agvhd or cgvhd (p=0.023) and transplant year after 2000 (p=0.01). In multivariate analysis age above 50 (RR: 1.8, 95%CI: 1.2-1.8, p=0.046) and RIC (RR: 4.4, 95% CI: 1.2-8.3, p=0.03) were independently associated with higher risk of SSC. In autograft group, there were no independent risk factors in univariate or multivariate analysis. As compared to general population incidence was higher for all cancers (SIR=7.4) and also cancers at every primary site. Risk was highest for breast (SIR=14.3), Head/neck (SIR=25.6), brain (SIR=17.4) and colon (SIR=6.2). Overall survival is significantly shorter in patients who develop SSC (median: 12 yr vs. not reached, p<0.0001). The median time to develop SSC from the date of HSCT has significantly shortened over last three decades (years 1982-1990: 21yr, 1991-2000: 11.1 yr, 2001-2010: 6.34 yr, 2011-2016: 2.2 yr; p=0.0001) Conclusion: This single centre analysis confirms that the risk of developing SSC increases with advancing age, use of RIC allograft, longer follow-up and leads to inferior survival. Since the year 2000, SSC are developing early after transplant and it needs to be evaluated if this is a trend seen at other centers and if so, is it related to increasing use of RIC, increasing number of elderly patients, severity of immune-suppression or higher incidence of GVHD. Disclosures Somervaille: Novartis: Consultancy, Honoraria; Imago Biosciences: Consultancy. Bloor:Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; GSK: Consultancy, Speakers Bureau; Gilead: Honoraria; Abbvie: Membership on an entity's Board of Directors or advisory committees.

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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