9-year follow-up of patients with relapsed follicular lymphoma after nonmyeloablative allogeneic stem cell transplant and autologous transplant

2021 ◽  
pp. clincanres.1377.2021
Author(s):  
Issa F. Khouri ◽  
Denai R. Milton ◽  
Alison M. Gulbis ◽  
Elias J. Jabbour ◽  
Loretta Nastoupil ◽  
...  
Keyword(s):  
Stem Cell ◽  
Follicular Lymphoma ◽  
Stem Cell Transplant ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Autologous Transplant

Characteristics and Outcome of Patients with Acute Myeloid Leukemia (AML) Refractory to One Cycle of High Dose Cytarabine-Based Induction Chemotherapy.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1038-1038
Author(s):  
Farhad Ravandi ◽  
Jorge Cortes ◽  
Stefan Faderl ◽  
Susan O'Brien ◽  
Guillermo Garcia-Manero ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplant ◽  
Conflicts Of Interest ◽  
Single Agent ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Refractory Disease ◽  
Allogeneic Stem Cell Transplant

Abstract Abstract 1038 Poster Board I-60 Background: Outcome of patients (pts) with AML refractory to initial induction is assumed to be poor but the available data is limited. Furthermore, pts refractory to standard dose cytarabine-based regimens may be salvaged with high dose ara-C (HiDaC, defined as daily ara-C dose ≥ 1 g/m2). Information on the outcome of pts refractory to initial HiDaC - based induction is more limited. Aim To better characterize predictors of poor response to HiDaC-based induction and to evaluate the outcome of pts refractory to such induction regimens. Methods: We identified pts treated with induction regimens containing HiDaC at the University of Texas – M D Anderson Cancer Center who did not achieve a compete remission (CR) after one cycle of induction. We examined their pre-treatment characteristics and compared them with similar pts achieving a CR. We also examined their response to salvage chemotherapy and outcome. Results: Among 1179 pts treated with HiDaC-based induction therapy from 1995 to 2009, 285 were primary refractory to one course of induction. Their median age was 59 (range, 18 - 85). Median pretreatment WBC was 9.0 × 109/L (range, 0.3 – 394 × 109/L). Cytogenetics included-5/-7/complex 101 (35%), diploid 85 (30%), other intermediate 98 (34%), favorable 1 (<1%). 165 (58%) pts had antecedent hematological disorder. Induction regimens used included HiDaC with anthracyclines (n=181, 64%), HiDaC with non-anthracycline chemotherapy (fludarabine, clofarabine, topotecan, and troxacitabine) (n=104, 36%) Pts with primary refractory disease were older (Median age 59 vs. 56; p=000004), more likely to have chromosome 5/7 or complex cytogenetic abnormalities (P=0.0001), more likely to have AHD (p=0.0001), and had a higher presentation WBC (P=0.036), but not a higher incidence of FLT3 mutations (p=0.85) than those achieving CR. Primary refractory disease was not more likely with non-anthracycline containing regimens than those with anthracyclines (p=0.58). Salvage chemotherapy included combination chemotherapy in 111 (39%)(non-ara-C regimen in 40, containing ara-C in 71), single agent chemotherapy in 64 (22%), allogeneic stem cell transplant in 22 (8%) and none in 88 (31%). Forty-three (15%) pts responded to salvage including 35 CR and 8 CRp. 114 (58%) pts were resistant and 35 (18%) died; 5 (3%) were lost to follow-up. With a median follow-up of 115 weeks (range 8 – 347 weeks) in pts responding to salvage, 21 pts (7%) were alive and in CR, for at least 6 months including 14 who underwent an allogeneic stem cell transplant (median overall survival for these 21 pts, 30 months; range, 13 to 87 months). Conclusions: Outcome of pts with disease refractory to HiDaC-based induction is poor. Alternative strategies are needed in these pts who are likely to be resistant to standard chemotherapy. Disclosures: No relevant conflicts of interest to declare.

Allogeneic Stem Cell Transplant Versus Tandem High-Dose Melphalan for Front-Line Treatment of Deletion 13q14 Myeloma – An Interim Analysis of the German DSMM V Trial.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 51-51 ◽  
Author(s):  
Stefan Knop ◽  
Peter Liebisch ◽  
Holger Hebart ◽  
Ernst Holler ◽  
Monika Engelhardt ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Interim Analysis ◽  
Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
High Dose Melphalan

Abstract Abstract 51 Background Allogeneic stem cell transplantation (allo SCT), a treatment modality based on transfer of immunocompetent donor lymphocytes offers curative potential to subjects with a variety of hematological cancers. In multiple myeloma (MM), high-dose melphalan followed by autologous stem cell transplantation (auto SCT) is adopted as a standard of care. However, it remains palliative since virtually all patients (pts) relapse and renders allo SCT an option of interest. Deletion of chromosome 13q14 (13q-) in MM has been shown to negatively impact prognosis. Therefore, improvement of therapy for 13q- pts is highly desirable. Patients and methods A prospective two-arm multi-center trial (DSMM V) was set up by our group to compare tandem high-dose melphalan 200 mg/m2 (HD Mel) with a reduced intensity conditioning allo-SCT after one cycle of HD Mel for 13q- MM. Eligibility criteria were 13q- on bone marrow FISH analysis; age up to 60 years; newly diagnosed MM in Salmon and Durie stages II and III; and measurable disease. Allocation to either treatment arm was by availability of an HLA-matched (one mismatch allowed) volunteer related (VRD) or unrelated donor (VUD). Initially, all pts received four cycles of anthracycline/dexamethasone-based induction followed by chemomobilization of peripheral blood stem cells (PBSCT) and one cycle of HD Mel. Allogeneic SCT was performed after preparation with fludarabine (30 mg/m2 for 3 consecutive days) and melphalan 140 mg/m2. ATG was administered for VUD transplants. Results 199 pts with a median age of 53 (range, 30 – 60) years were enrolled between October 2002 and March 2007 and included in this interim analysis. Sixty-seven percent had stage III disease. Allo SCT was performed in 126 of 199 pts (63%), 76 of whom (60%) received VUD allografts. The remaining 73 subjects uniformely received tandem HD Mel. Pts following allo SCT were more likely to achieve CR (59%) when compared to tandem HD Mel (32%; p=.003) within one year after end of therapy. Similarly, overall response rate was significantly higher with allo SCT (91% versus 86%; p=.003). Of note, depth of response to allo SCT was not associated with presence of acute graft-versus-host disease (GVHD): 62% CR with grades II to IV GVHD vs 58% CR with grades 0 and I (p=.75). Treatment-related mortality (TRM) at 2 years from allo SCT was 16/126 (12.7%). At a median follow up of 25 months for tandem HD Mel and 34 months for allo SCT, projected 3-year overall survival is 72% (auto) and 60% (auto/allo SCT; p=0.22), respectively. Conclusions This is the largest trial on first-line allogeneic stem cell transplant in MM so far. Our interim results show a higher CR rate in FISH 13q- subjects undergoing allo SCT when compared to tandem HD Mel. Despite a majority of allografts in our study being delivered from unrelated donors, TRM was comparable to trials confined to sibling transplants. At a relatively short follow-up, there is not yet a difference between both arms regarding OS, albeit longer follow-up may be important as previously described. This as well as analysis of the impact of donor type and chronic GVHD on outcome will be presented at the meeting. Disclosures: No relevant conflicts of interest to declare.

Philadelphia Positive Acute Lymphoblastic Leukemia (Ph+ ALL), Tawam Experience

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4867-4867
Author(s):  
Arif Alam ◽  
Khaled al Qawasmeh ◽  
Jihad Kanbar ◽  
Masood H Syed ◽  
Amar Lal ◽  
...  
Keyword(s):  
Stem Cell ◽  
Acute Lymphoblastic Leukemia ◽  
Stem Cell Transplantation ◽  
Stem Cell Transplant ◽  
Lymphoblastic Leukemia ◽  
Philadelphia Chromosome ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Molecular Remission

Abstract Acute lymphoblastic leukemia (ALL) is a relatively rare lymphoid disorder with approximately 11 cases per million persons per year in United States. It is seen more commonly in children however adults are also affected with the median age approximately 39 years. The prognosis is influenced by the age of the patient and genetic findings. Abnormal cytogenetic is present in approximately 80 % of the patients. Philadelphia chromosome t (9;22) is seen in approximately 30 % of adult patients (Ph + ALL) and imparts a poor prognosis. Allogeneic stem cell transplant remains one of the corner stones of therapy along with Tyrosine Kinase Inhibitors TKIs (Imatinib or Dasatinib). Patients who are unable to go for transplant are kept on TKIs and continue consolidation and maintenance chemotherapy. In this retrospective review, we present patients with Philadelphia chromosome positive ALL seen at our institute and their outcomes. Tumor registry data base was searched for adult patients with ALL between January 1st 2010 and June 30th 2015. Forty patients were identified with B cell ALL and ten patients were diagnosed with Ph+ ALL (25 % of the cohort). The median age was 30 years (range 18 - 73 years). Male to female ratio was 4.5:1 Induction therapy was given based on UK ALL protocol. Tyrosine kinase inhibitor (Imatinib) was added when information regarding BCR-ABL translocation status was available. Interestingly 8 out of the 10 Ph+ patients also had CD 20 positive disease and were treated with rituximab in addition to standard chemotherapy and TKI. Two patients were lost from follow-up after receiving initial therapy and achieving remission. Four patients had HLA identical siblings and were able to go for allogeneic stem cell transplant. With a median follow up of 28 months (range 1 to 57 months), 3 of the 4 patients are alive and in complete molecular remission. One patient relapsed 19 months post-transplant and died of complications of a 2nd transplant. The remaining 4 patients were unable to go for allogeneic stem cell transplant. They were treated with Hyper-CVAD regimen and Dasatinib (Rituximab was used in patients with CD 20 positive clone). One patient died of colitis and relapsed ALL (36 months post diagnosis) while the other 3 patients are alive and on active therapy, all being in complete molecular remission. Discussion: This is the first report of incidence, management and outcome of Ph+ ALL from UAE. Ph + ALL contribute to 25 % of the cohort of ALL patients in our center. Majority of this cohort was also CD 20 positive. All patients achieved a complete hematologic remission after induction therapy. However, less than half of the patients were able to go for allogeneic stem cell transplantation as consolidation due to different reasons. Post transplantation use of TKI remains variable. HyperCVAD and Dasatinib appears to be a reasonable but toxic alternative for patients who are unable to go for allogeneic stem cell transplantation with a reported estimated survival of 64 % at 2 years interval. Disclosures No relevant conflicts of interest to declare.

Efficacy of Idelalisib as Bridge to Allogeneic Stem Cell Transplant in Relapsed Follicular Lymphoma: A Case Report

2017 ◽  
Vol 103 (1_suppl) ◽  
pp. S41-S43 ◽  
Author(s):  
Miriam Marangon ◽  
Cinzia Pellegrini ◽  
Lisa Argnani ◽  
Pier Luigi Zinzani
Keyword(s):  
Stem Cell ◽  
Case Report ◽  
Follicular Lymphoma ◽  
Stem Cell Transplant ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Effective Treatment Option

Purpose A large number of new therapeutic agents have been studied for patients with relapsed/refractory follicular lymphoma (FL). Among new therapies, idelalisib, a novel PI3K inhibitor, shows promising results in the management of this disease. Case report We describe the case of a 39-year-old patient with a diagnosis of grade 3a FL and a Follicular Lymphoma International Prognostic Index score of 2, who underwent several lines of therapy (including autologous stem cell transplant) with transient responses or no response at all. The patient was subsequently treated with 5 courses of idelalisib monotherapy, achieving a partial response. No relevant toxicities occurred. The patient underwent allogeneic stem cell transplant (allo-SCT) from an unrelated donor and obtained a complete response, which was confirmed after 3, 6, 9, and 12 months, and is still ongoing. Conclusions As previously reported, the achievement of a good response is predictive for a better outcome after allo-SCT: idelalisib represents an effective treatment option for patients with relapsed/refractory FL, which can also be adopted as a bridge to allo-SCT.

Clinical Profile and Outcomes of Patients with β Thalassemia Major and Hepatitis C Virus Infection Undergoing an Allogeneic Stem Cell Transplant

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4160-4160
Author(s):  
Vikram Mathews ◽  
Biju George ◽  
Kavitha M Lakshmi ◽  
Rayaz Ahmed ◽  
Aby Abraham ◽  
...  
Keyword(s):  
Risk Factors ◽  
Stem Cell ◽  
Graft Failure ◽  
Stem Cell Transplant ◽  
Thalassemia Major ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
Class Iii ◽  
Liver Size

Abstract Abstract 4160 There is limited data on the prevalence, clinical profile and outcome of patients with β thalassemia major (TM) who is HCV sero-positive (HCV+) prior to an allogeneic stem cell transplant (SCT). From October, 1991 to June, 2012, 370 SCT were done for TM at our center. The median age was 7.5 years (range: 2–24) and there were 232 (62.87%) males. 209 (56.5%) belonged to Lucarelli Class III. There were 44 (11.9%) cases who were HCV+, 6 (1.6%) who were HBsAg positive and 350 (94.6%) who were CMV sero-positive at the time of pre-transplant screening. HCV+ cases were significantly older and had a significantly larger liver size. There were significantly more number of HCV+ cases who were Lucarelli Class III and the median liver enzyme and ferritin levels were higher in the HCV+ group. Table 1 summarizes these and other major differences between those who were HCV positive at diagnosis and the remaining patients. The number of graft rejections was significantly higher in the HCV+ group while the TRM was comparable between the two groups. This translated into a significantly inferior event free survival (P=0.016) though the overall survival was not significantly different (P=0.140)(Table 1). It is well recognized that patients with TM are at a high risk of developing sinusoidal obstruction syndrome (SOS) post SCT. In this series, 165 (4.6%) patients developed SOS. HCV+ cases did not have a significantly higher incidence of SOS compared to those that were HCV negative. In only 3 (6.8%) of HCV+ cases was SOS the major cause of death while SOS was a major contributory factor for death in 17 (5.2%) of the remaining cases. Among the 15 (34%) of HCV+ cases that died, the major contributory cause of death was infection (40%), graft failure (20%) and SOS (20%). On a univariate cox regression analysis, HCV+ had an adverse impact on EFS (RR=1.710; 95%CI 1.066–1.744; P=0.026). However, on a forward stepwise multivariate analysis after adjusting for conventional risk factors HCV+ status did not confer an independent adverse risk factor. Of the 29 patients who are surviving, at a median follow up of 25 months, none have had progression to chronic liver disease. 20 (69%) had a normal liver function test at last follow up while only 3 have had HCV directed therapy post transplant. From August, 2009 at our center we have been using a treosulfan based conditioning regimen for our Class III patients. Among the HCV+ cases 10 were conditioned with this regimen. This regimen was well tolerated with 100% engraftment. Two patients died, one due to sepsis and the other to GVHD. In comparison, in the historical control of HCV+ cases conditioned with a conventional busulfan based regimen where there were graft rejections in 9 (26.4%) and 13 (38.2%) deaths, the major contributory cause for death being infections (46%), SOS (23%) and graft failure (23%). In conclusion HCV+ status is a surrogate risk factor for other adverse risk factors such as older age, increased liver size and inadequate medical therapy prior to SCT. After adjusting for such risk factors HCV+ cases with TM undergoing an allogeneic SCT transplant have comparable outcomes to HCV negative cases. Use of a treosulfan based regimen is well tolerated in the HCV+ group and could potentially improve the outcome in this high risk group. Table 1: Comparison of baseline characteristics and clinicical outcomes of HCV positive and vegative cases with β thalassemia major undergoing an allogeneic stem cell transplant. Disclosures: No relevant conflicts of interest to declare.

High Dose Cytarabine and Mitoxantrone in Combination with Dasatinib As Active Induction Therapy in Adult Patients with Philadelphia Chromosome Positive (ph+) Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4293-4293
Author(s):  
Nicole Lamanna ◽  
Mark Weiss ◽  
Ellin Berman ◽  
Mark G. Frattini ◽  
Mark Heaney ◽  
...  
Keyword(s):  
Stem Cell ◽  
Dose Level ◽  
Induction Therapy ◽  
Stem Cell Transplant ◽  
Philadelphia Chromosome ◽  
High Dose ◽  
Cell Transplant ◽  
Allogeneic Stem Cell Transplant ◽  
High Dose Cytarabine

Abstract Abstract 4293 Introduction: The Philadelphia chromosome is the most frequent cytogenetic abnormality in adult ALL, with an overall incidence of 20–30%. When treated with conventional therapy, adult patients with Ph+ ALL have an extremely poor prognosis. While current chemotherapy regimens typically induce complete responses (CRs) in the majority of patients, the quality of remission is poor as most patients relapse within 6–11 months of treatment and subsequently die from the disease. The 1 and 5-year overall survival rates for patients treated with imatinib-based chemotherapy regimens is approximately 60% and 30%, respectively. Previously we in collaboration with others have reported a Phase III randomized study of high-dose cytarabine and mitoxantrone (ALL-2 regimen) as induction therapy versus a more traditional treatment regimen with vincristine-prednisone based induction therapy in newly diagnosed adult ALL patients (Weiss, ASCO 2005). This study was conducted prior to the routine use of tyrosine kinase inhibitors (TKIs) for Ph+ disease. In that randomized study, there were 16 patients with Ph+ ALL treated with the frequency of CRs on the ALL-2 regimen 85% compared to 47% of patients treated on the vincristine-prednisone based arm. At 6 year follow-up, 26% of Ph+ patients treated with the ALL-2 regimen were alive compared to 0% of Ph+ ALL patients treated on the vincristine-prednisone induction arm. Based on this initial favorable response seen with the ALL-2 regimen in Ph+ patients and the emerging use of TKI therapy in Ph+ALL, dasatinib was added to this therapeutic regimen. This is the first report of this combination in newly diagnosed patients with Ph+ ALL or blastic phase CML patients. Methods: Eligible patients included previously untreated or treated adults with a diagnosis of Ph+ ALL or lymphoid blast crisis of known CML. Patients must have evidence of t(9;22) in leukemic cells based on chromosomal or molecular analysis. Patients received induction therapy with high-dose cytarabine (3000 mg/m2 IVPB daily, days 1–5) and mitoxantrone (80mg/m2 IVPB on day 3 for patients ≤ 65 yrs or 40mg/m2 for patients >65 yrs) in combination with dasatinib. Patients in the phase I portion of the study were assigned to one of 3 successive dose cohorts of dasatinib: dose level 1: 70mg daily, dose level 2: 100mg daily; dose level 3: 140mg daily, starting on day 1. Patients then received treatment with Consolidation A: vincristine, dexamethasone, and dasatinib. Following consolidation A, patients who achieved a CR and were ≤ 70 years of age and had a suitable HLA donor were referred for allogeneic stem cell transplant. The remaining patients continued consolidation and maintenance therapy per the ALL-2 regimen with dasatinib as per protocol. Results: Seven patients with Ph+ disease were enrolled between 3/2010-11/2011 (Table 1). All (100%) achieved complete remission after induction; 6 of the seven patients (86%) were in both cytogenetic and molecular remission. Although the numbers are small, there does not seem to be a difference in response depending upon the dose level of dasatinib administered. One patient was taken off study due to recurrent gastrointestinal issues but continued to be followed for response and survival and completed induction therapy as per protocol. Six of the seven patients (86%) went on to receive allogeneic stem cell transplant in first remission. The patient who was ineligible for allogeneic stem cell transplant due to multiple comorbidities continues on maintenance chemotherapy as per protocol. Two patients have died in remission due to post transplant complications. One patient became MRD positive post-transplant and is on nilotinib therapy. Median overall survival has not been reached with median follow-up greater than 20 months. Conclusions: The addition of dasatinib to high-dose cytarabine and mitoxantrone induction therapy for patients with Ph+ ALL is tolerable and efficacious. Patients achieved a higher frequency of CRs compared to our historical study that did not use TKI-based therapy in this patient population. Long-term follow-up of these patients is ongoing. Disclosures: Lamanna: Bristol Meyers Squibb: Research Funding. Off Label Use: dasatinib as part of initial therapy for patients with Philadelphia chromosome + ALL.

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