scholarly journals Reduced-Intensity Allogeneic Transplantation Provides High Event-Free and Overall Survival in Patients with Advanced Indolent B Cell Malignancies: CALGB 109901

2011 ◽  
Vol 17 (9) ◽  
pp. 1395-1403 ◽  
Author(s):  
Thomas Shea ◽  
Jeffrey Johnson ◽  
Peter Westervelt ◽  
Sherif Farag ◽  
John McCarty ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Allogeneic Transplantation ◽  
B Cell Malignancies ◽  
High Event ◽  
Reduced Intensity

Outcome of Adults with Acute Lymphoblastic Leukemia Treated with a Pediatric-Inspired Therapy: A Single Institution Experience

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4337-4337
Author(s):  
Guillermo J. Ruiz-Delgado ◽  
Julio Macias-Gallardo ◽  
Julia Lutz-Presno ◽  
Maryel Montes-Montiel ◽  
Guillermo J. Ruiz-Arg\)elles
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Single Institution ◽  
B Cell Malignancies ◽  
Secondary Diabetes ◽  
Free Survival ◽  
Results Of Treatment ◽  
Better Than

Abstract Abstract 4337 The results of treatment of adults with ALL remain unsatisfactory. Pediatric-inspired treatments seem to be related with better outcomes. Eighty adult ALL patients were prospectively treated in a single institution in a 16-year period with a schedule based on the St. Jude's TOTAL XI pediatric protocol employing vincristine, prednisone, asparaginase, daunorubicin, etoposide, cytarabine, methotrexate, mercaptopurine and triple intratecal therapy. Median age was 31 years (range 18 – 86); 92% were B-cell malignancies and 14% were Ph1 (+). Ten patients did not complete the first course of chemotherapy and 4 exited early. 44 of 66 patents (67%) achieved a complete remission; relapses presented in 57%. The median probability of overall survival (OS) was 28 months, whereas the 144-month OS was 27%. The median probability of leukemia-free survival (LFS) was 28 months, and the 144-month LFS 35%. Ph1 (+) patients did worse than Ph1-negative and T-cell leukemias did better than B-cell ones. Concerning toxicity, eight patients had toxic deaths (12%), two developed acute pancreatitis and one secondary diabetes. This pediatric-inspired therapy rendered better results than those obtained in similar socioeconomic circumstances using adult-oriented treatments; tolerance was acceptable and costs were low since it employs affordable drugs and can be delivered as outpatients. Disclosures: No relevant conflicts of interest to declare.

Improved Outcome Following Reduced Intensity Allogeneic Transplantation in Hodgkin’s Lymphoma Relapsing Post-Autologous Transplantation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 657-657 ◽  
Author(s):  
Kirsty J. Thomson ◽  
Karl S. Peggs ◽  
Paul Smith ◽  
Raj Chopra ◽  
Jim Cavet ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hodgkin’S Lymphoma ◽  
Autologous Transplantation ◽  
Allogeneic Transplantation ◽  
Hodgkin's Lymphoma ◽  
Reduced Intensity Conditioning ◽  
Actuarial Survival ◽  
Group A ◽  
Group B ◽  
Reduced Intensity

Abstract Hodgkin’s Lymphoma is curable with primary therapy in the majority of patients. For those with relapsed or refractory disease, salvage with high dose chemotherapy plus autologous stem cell rescue is effective for a significant proportion. Patients relapsing following autologous stem cell transplantation, however, have an extremely poor prognosis. Allogeneic transplantation with conventional conditioning has proved excessively toxic in this setting, and reduced intensity conditioning has therefore been introduced, with encouraging preliminary results. This is a study of 72 patients relapsing following autologous transplantation, analysed in 2 groups. One group (A: n=38) then underwent allogeneic transplantation with reduced intensity conditioning at 6 UK centres (1998–2004), with alemtuzumab 100mg, fludarabine 150mg/m2 and melphalan 140mg/m2. Donors were HLA-matched related in 63% of cases, and unrelated in the remaining 37%. The second group (B: n=34) is a control cohort, who relapsed before the advent of reduced intensity conditioning, and were treated with chemotherapy +/− radiotherapy alone. The groups were equivalent in age (median- A 31yrs [20–51]; B 29yrs [13–47]), disease subtype (>85% nodular sclerosing both groups), time from diagnosis to autograft (median-A 18mo [7–139]; B 20mo [4–185]), and lines of prior therapy pre-autograft (median 3 both groups). Median time from autograft to relapse for group A was 13mo (2–56) and for group B 10mo (3–40), and patients were only selected for inclusion in group B if they responded to further salvage therapy, attained at least a stable response to treatment, and lived for >12 months following relapse (median time from relapse to allogeneic transplant for group A is <12 months). In this way, it was intended to include only those patients who would have been eligible for reduced intensity allogeneic transplantation had this been available at the time. Indeed, the entry criteria for group A were arguably less stringent, as patients with chemorefractory disease were included (n=14, 37%). Overall survival from diagnosis was significantly better in group A, with actuarial survival at 10yrs of 48% compared to 15% in group B (p=0.0014), and overall survival from autograft was 65% at 5 yrs in group A and 15% in group B (p=<0.0001). Of group B patients treated with chemotherapy/RT alone, only 2/34 patients remain alive at a median follow-up of 22 months from relapse, one of whom has progressive disease. For group A receiving reduced intensity transplantation, actuarial survival from the time of allograft was 50% at 5 yrs. In the chemoresponsive patients, OS at 5yrs was 57% at 5 yrs with current progression-free survival of 39% at 5 yrs. This demonstration of the potential efficacy of reduced intensity transplantation in a group of heavily pre-treated patients who have failed autograft and whose outlook is otherwise extremely poor, strongly suggests further studies of reduced intensity allogeneic transplantation in Hodgkin’s Lymphoma are warranted.

Prolonged survival in adults with acute lymphoblastic leukemia after reduced-intensity conditioning with cord blood or sibling donor transplantation

Blood ◽  
2009 ◽  
Vol 113 (13) ◽  
pp. 2902-2905 ◽  
Author(s):  
Veronika Bachanova ◽  
Michael R. Verneris ◽  
Todd DeFor ◽  
Claudio G. Brunstein ◽  
Daniel J. Weisdorf
Keyword(s):  
Overall Survival ◽  
Acute Lymphoblastic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Lymphoblastic Leukemia ◽  
Allogeneic Transplantation ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Preparative Regimen ◽  
Total Body ◽  
Reduced Intensity

Abstract Twenty-two adult acute lymphoblastic leukemia (ALL) patients (21 of 22 in complete remission [CR]) received reduced-intensity conditioning followed by allogeneic transplantation. All patients were high risk. After a uniform preparative regimen (fludarabine 40 mg/m2 × 5, cyclophosphamide 50 mg/kg, 200 cGy total body irradiation), patients received either matched related (n = 4) or umbilical cord (n = 18) donor grafts. All patients reached neutrophil engraftment and 100% donor chimerism (median, days 10 and 23, respectively). Overall survival, treatment-related mortality (TRM) and relapse were 50% (95% confidence interval [CI], 27%-73%), 27% (95% CI, 9%-45%), and 36% (95% CI, 14%-58%) at 3 years, respectively. There were no relapses beyond 2 years. The cumulative incidence of acute and chronic graft-versus-host disease was 55% and 45%. Hematopoietic cell transplantation in CR1 (n = 14) led to significantly less TRM (8%, P < .04) and improved overall survival (81%, P < .01). For adults with ALL in CR, reduced intensity conditioning allografting results in modest TRM, limited risk of relapse, and promising leukemia-free survival. Clinical trial numbers are NCT00365287, NCT00305682, and NCT00303719.

scholarly journals Prognostic Impact of Peripheral Blood Count Recovery and Cytogenetic Remission Prior to Reduced Intensity Allogeneic Transplantation in Patients with Acute Myelogenous Leukemia and Myelodysplastic Syndromes

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3210-3210 ◽  
Author(s):  
Moussab Damlaj ◽  
Hassan B Alkhateeb ◽  
Mehrdad Hefazi ◽  
Daniel K. Partain ◽  
Aref Al-Kali ◽  
...  
Keyword(s):  
Overall Survival ◽  
Complete Remission ◽  
Acute Myelogenous Leukemia ◽  
Allogeneic Transplantation ◽  
Myelogenous Leukemia ◽  
Transplant Outcomes ◽  
Acute Myelogenous ◽  
The Impact ◽  
Reduced Intensity ◽  
Count Recovery

Abstract Background:Morphologic complete remission (CR) is the gold standard for assessing response in acute myelogenous leukemia (AML). CR with incomplete count recovery (CRi) and CR with incomplete platelet recovery (CRp) are associated with inferior overall survival post induction therapy (Walter et al, JCO 2010 and Chen et al, JCO 2015). Furthermore, residual cytogenetic disease is associated with a higher relapse compared with patients with cytogenetic CR (CCR; Chen et al, JCO 2011). There is a paucity of literature regarding the impact of CRi, CRp and CCR prior to allogeneic transplantation. Aim:To study the impact of CRi, CRp and CCR and their impact on relapse incidence (RI), non-relapse mortality (NRM) and overall survival (OS) in reduced intensity allogeneic stem cell transplantation (RIC-SCT). Methods:After due IRB approval, patients (pts) with acute myelogenous leukemia (AML) or myelodysplastic syndrome (MDS) who received RIC-SCT at our institution between 2008-2014 were identified. All clinical and pathologic data were retrospectively extracted. CR, CRi, CRp and CCR were defined in accordance to the international working group definition. Categorical and continuous variables were analyzed using Pearson's chi-squared and Wilcoxon/Kruskal-Wallis, respectively. Survival estimates were calculated using the kaplan-meier and log-rank test. RI was estimated on a competing event analysis using Grey's model. Cox proportional regression was used to compute hazard ratios (HR). Results: A. Baseline characteristics: A total of 134 patients were identified. A total of 70 (52%) were in CR, 40 (30%) in CRi and 24 (18%) in CRp. 129 patients had evaluable cytogenetic data pre-SCT; 81 (63%) were in CCR and 48 (37%) had persistent cytogenetic disease. Baseline patient, disease and transplant characteristics stratified by peripheral count recovery pre-SCT are shown (Table 1). Significantly more patients in CR had higher KPS, higher proportion AML diagnosis, more likely to be in first complete remission (CR1), higher rate of cytogenetic CR and a higher proportion of minor ABO mismatched donor. No other significant variables were identified between the three cohorts. B. Transplant outcomes: Median follow up of the entire cohort was 41.9 months and the 2-yr OS, RI and NRM were 61.7%, 25.7% and 21.9%. Patients in CR, CRi and CRp had a similar 2-year rates of RI (26.3%, 18.4% and 28.9%, respectively; p = 0.66), 2-year NRM (20.5%, 38.8% and 22.1%, respectively; p = 0.18) and 2-year OS (61.8%, 55.1% and 58.6%, respectively; p = 0.82). RI was significantly lower for patients in CCR pre-SCT with HR 0.25 (95% CI 0.11-0.51 p = 0.0001) without a difference in overall survival HR 0.68 (0.41-1.15; p = 0.14). However, we observed a similar RI in CR, CRi and CRp patients who had persistent cytogenetic disease pre-SCT (p = 0.55). The outcome remained similar between strata after excluding MDS patients (data not shown). Conclusion: We observed equivalent post-transplant outcomes between CR, CRi and CRp despite the presence of persistent cytogenetic disease. This suggests that RIC SCT had a role in mitigating the negative prognosis associated incomplete hematologic recovery. These findings have implications as physicians may not need to postpone SCT to await count recovery. This important question should be further validated in a larger cohort of patients. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Al-Kali: Novartis: Research Funding.

Retherapy with Bendamustine-Containing Regimens in Patients with Relapsed/Refractory CLL and Indolent Lymphomas Achieves High Response Rates

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1615-1615
Author(s):  
Rudolf Weide ◽  
Stefan Feiten ◽  
Vera Friesenhahn ◽  
Jochen Heymanns ◽  
Kristina Kleboth ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Overall Response Rate ◽  
Conflicts Of Interest ◽  
Response Rates ◽  
High Response ◽  
B Cell Malignancies ◽  
The Mean ◽  
Grade 3 ◽  
Indolent Lymphomas

Abstract Abstract 1615 Purpose: Bendamustine-containing regimens have shown high response rates and long lasting remissions in relapsed/refractory indolent B-cell-malignancies. Here we have evaluated the efficacy of Bendamustine-containing regimens as retherapy in this patient population. Patients and methods: Patients with CLL or indolent B-cell-malignancies (NHL) who previously had been treated with Bendamustine and were retreated with either Bendamustine (90mg/m2, day 1+2, q day 29 (1–6 cycles)) (B) or Bendamustine (90mg/m2, day 1+2) + Mitoxantrone (6–10mg/m2, day 1), q day 29 (1–4 cycles) (BM) or Bendamustine (90mg/m2, day 1+2) + Rituximab (375mg/m2, day 1), q day 29 (1–6 cycles) (BR) or Bendamustine (90mg/m2, day 1+2) + Mitoxantrone (6mg/m2 day 1) + Rituximab (375mg/m2, day 8,15,22,29) (BM was repeated on day 36 × 1–3 every 4 weeks) (BMR) between 2000–2010 were analyzed retrospectively. Data were collected from patient files into a database and analyzed statistically using SPSS. Results: 88 patients (57 CLL, 31 NHL) received a Bendamustine-retherapy-regimen. The median age at the first Bendamustine retherapy was 72 years (50–88). The mean number of therapies per patient was 6.0 in CLL and 7.0 in NHL; the mean number of Bendamustine therapies was 3.0 in CLL and 2.6 in NHL. Bendamustine-containing retherapy consisted of B in 4%, BM in 12%, BR in 29% and BMR in 55%. The overall response rate of Bendamustine retherapy was 79% (9% CR, 70% PR). ORR according to regimen was as follows: B: 57% (14% CR, 43% PR), BM: 70% (4% CR, 66% PR), BR: 55% (10% CR, 45% PR), BMR: 84% (7% CR, 78% PR). Main toxicity was a reversible grade 3 or 4 hematotoxicity in 35% of retherapies! No therapy associated death was observed. Overall survival since first diagnosis was 134 months in CLL (23–187) and 131 months in NHL (20–339). Overall survival since start of Bendamustine-containing retherapy was 33 months in CLL (2–129+) and 23 months in NHL (2–62+). Conclusion: Bendamustine-containing retherapy-regimens achieve high response rates in patients with relapsed/refractory CLL and NHL. Hematotoxicity is relevant but reversible. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Improved Outcome and Decreased Morbidity and Mortality Rates of B-Cell Malignancies with Less Intensive Chemotherapy Induction: Experience in a Single Institution

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1858-1858 ◽  
Author(s):  
Cristian G Sanchez La Rosa ◽  
Myriam Guitter ◽  
Alfaro Elizabeth ◽  
Natalia Millan ◽  
Jorge Gabriel Rossi ◽  
...  
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Tumor Lysis Syndrome ◽  
Mortality Rates ◽  
Morbidity And Mortality ◽  
High Dose ◽  
Induction Phase ◽  
B Cell Malignancies ◽  
Early Phases ◽  
Reduced Intensity

Abstract Background: High-Dose chemotherapy is necessary one of the most important tools for improving response rates and for decreasing relapse rate in childhood B-cell malignancies. However, deaths during induction or in Complete Remission (CR) in children with higher disease burden had adversely influenced pEFS in our setting, and for this reason an accomplished clinical support is mandatory for achieving these better results. Objective: Our aim was to diminish morbidity and mortality of patients with B-cell malignancies with the administration of a reduced intensity BFM-based induction phase, plus the addition of rituximab in a pilot study. We also retrospectively analyzed the outcome of this group of patients. Methods: This is a prospective study, single arm, non-randomized local trial for treatment of B-cell malignancies. Between December-2008 and March-2016, 81 pts consecutive (<16 years/old) (52:M/29:F) were enrolled in a protocol HPG-09, and 70 of them resulted evaluable. Patients were stratified according stage and DHL level in Risk-1, Risk-2, Risk-3 and Risk-4. Risk-4 included patients with stage IV and stage III with DHL levels higher than 1,000 U/dl. The pathology, flow-cytometry and cytogenetic findings disclosed 60 cases of Burkitt Lymphoma, 11 diffuse large B cell Lymphomas, 9 mature-B acute lymphoblastic leukemia, and 1 Precursor-B ALL with with t(8;14). The treatment locally-none BFM-counterpart included 4 doses of Rituximab administered to Risk-4 cases during early phases of treatment and intensified chemotherapy with HDMTX (24 hr) 5 g/m2, plus reduced intensity induction with pre-phase followed by A1 block (MTX 1 g/m2 4 hr infusion), in order to decrease morbidity and early mortality rates. Results: Distribution of patient according to risk-groups was: Risk-1 (n=2) 2%, Risk-2 (n=9) 11%, Risk-3: (n=13) 16% and Risk-4 (n=46) 57% of cases. Median DHL= 3,642 (range: 396-33,673) UI/dl, CNS+ cases was observed in 6 cases. Complete remission (CR) was achieved in 95.1% of the cases and 4.9% of patients died in early phases of treatment. From patient who achieve CR, 6 adverse events were observed (all of them in Risk-4 group): 2 relapses and 4 death in CR (1 Steven´s-Johnson Syndrome, 2 tumor lysis syndrome plus CID and 1 patient died after extensive initial surgery) The pEFS for R1, R2, and R3 was 100%. With a median follow-up of 48 (range:6-61) months, the pEFS (SE) for all risks groups was 91 (4)% and for Risk-4 85 (6)%. Conclusions: Risk-4 group accounted for 66% of the total population of patients, defining a more aggressive disease prevalence in our setting. Locally-adapted strategy based on BFM experience was successfully implemented, reducing induction intensity and with the incorporation of 4 doses of Rituximab. The outcome of this group of patients was very good. Reduction of induction intensity and addition of Rituximab resulted in low mortality rate and excellent survival outcome. Disclosures No relevant conflicts of interest to declare.

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