Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Relapsed, Refractory, and Transformed Indolent Non-Hodgkin's Lymphoma

2008 ◽  
Vol 26 (2) ◽  
pp. 211-217 ◽  
Author(s):  
Andrew R. Rezvani ◽  
Barry Storer ◽  
Michael Maris ◽  
Mohamed L. Sorror ◽  
Edward Agura ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Hodgkin's Lymphoma ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Non Hodgkin's Lymphoma ◽  
Indolent Disease

Purpose Few effective treatment options exist for chemotherapy-refractory indolent or transformed non-Hodgkin's lymphoma (NHL). We examined the outcome of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in this setting. Patients and Methods Sixty-two patients with indolent or transformed NHL were treated with allogeneic HCT from related (n = 34) or unrelated (n = 28) donors after conditioning with 2 Gy of total-body irradiation with or without fludarabine. Nine unrelated donors were mismatched for ≥ one HLA antigen. Sixteen patients had histologic transformation before HCT. Twenty patients (32%) had progressive disease after previous high-dose therapy with autologous HCT. Median age was 54 years, and patients had received a median of six lines of treatment before HCT. Median follow-up time after HCT was 36.6 months. Results At 3 years, the estimated overall survival (OS) and progression-free survival (PFS) rates were 52% and 43%, respectively, for patients with indolent disease, and 18% and 21%, respectively, for patients with transformed disease. Patients with indolent disease and related donors (n = 26) had 3-year estimated OS and PFS rates of 67% and 54%, respectively. The incidences of grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 and 4 acute GVHD, and extensive chronic GVHD were 63%, 18%, and 47%, respectively. Among survivors, the median Karnofsky performance status at last follow-up was 85%. Conclusion Nonmyeloablative allogeneic HCT can produce durable disease-free survival in patients with relapsed or refractory indolent NHL, even in this relatively elderly and heavily pretreated cohort. Outcomes were particularly good in patients with untransformed disease and related donors, whereas patients with transformed disease did poorly. Long-term survivors reported good overall functional status.

Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia (CLL) with 17p Deletion: A Retrospective EBMT Analysis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 47-47 ◽  
Author(s):  
Johannes Schetelig ◽  
Anja van Biezen ◽  
Dolores Caballero ◽  
Martino Rodrigo ◽  
Kari Remes ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Progressive Disease ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Median Interval

Abstract Purpose: Patients with advanced CLL and 17p deletion have a very poor prognosis even after intensive chemotherapy. While allogeneic hematopoietic cell transplantation (HCT) has the potential to cure patients with advanced CLL it is not known whether this holds true for patients with 17p deletion. Patients and Methods: Patients with 17p- CLL who had received HCT were identified by an EBMT-based survey. Baseline data were downloaded from the EBMT database. Additional information on the course of the disease, the cytogenetic diagnosis and last follow up was collected by a questionnaire. Data were analysed as of February 2007. Results: 56 patients were identified. Twelve patients with autologous HCT, haplo-identical donors or the detection of 17p- after HCT were excluded from further analysis. 44 patients had received an allogeneic HCT between March 1995 and July 2006 from a matched related donor (n=27) or unrelated volunteer donor (n=17). The median age at HCT was 54 years (range, 35 to 64 years). Until HCT the maximum stage had been Binet A or B in 37% of patients and Binet C in 61% of patients. The diagnosis of deletion 17p- was made by FISH in 82% and by conventional banding in 18% of patients. The median interval between first diagnosis and detection of 17p- was 2.3 years (range, 1 to 11 years) and the median interval between detection of 17p- and HCT was 0.5 years (range, 0 to 3 years). Patients had received a median of 3 chemotherapy regimens (range, 2 to 7 lines), including fludarabine in 93% of patients and alemtuzumab in 41% of patients. At HCT, 53% of patients were in remission while 47% of patients were in stable or progressive disease. Reduced intensity conditioning was applied in 89% of patients. Peripheral blood stem cells were transplanted in 93% of the patients. GVHD prophylaxis was performed heterogeneously. One patient experienced primary graft failure. Acute GVHD grades II to IV occurred in 44% of patients and extensive chronic GVHD in 46% of patients. After a median follow-up of 23 months (range, 2 to 90 months) of 26 patients who are alive, 18 were in complete remission, 4 in partial remission and 4 patients had progressive disease at last follow up. 4-year overall survival and progression-free survival was 48% (95% CI, 28% to 68%) and 37% (95% CI, 18% to 56%). The cumulative incidences of relapse and non-relapse mortality at 4 years were 36% and 27%. No late-relapse occurred in five patients with a follow-up of more than 4 years. Conclusion: Allogeneic HCT has the potential to induce long-term disease-free survival in selected patients with advanced 17p- CLL. Given the otherwise very dismal outcome of this disease, prospective studies on allogeneic HCT earlier in the course of 17p- CLL seem warranted.

Results of Second or Third Allogeneic Hematopoietic Cell Transplantation As Salvage Therapy for Patients Failing Primary Transplantation

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4516-4516
Author(s):  
Birgit Federmann ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
Wolfgang A. Bethge
Keyword(s):  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Free Survival ◽  
Off Label ◽  
Allogeneic Hct ◽  
Pre Treatment

Abstract Abstract 4516 Introduction: Patients with relapse after allogeneic hematopoietic cell transplantation (HCT) have generally a very poor prognosis. Besides donor lymphocyte infusions, chemotherapy or supportive care, second or even third allogeneic HCT have been performed in selected patients. This is often associated with a high incidence of non-relapse-mortality (NRM) because of heavy pre-treatment or reduced performance status due to comorbidities or pre-treatment related complications. Method: We report a retrospective analysis of our single center experience with second or third allogeneic HCT between 2000–2011. We searched our database for patients receiving >1 allogeneic HCT in the past 10 years. Details on characteristics and clinical course of the patients were confirmed by retrospective chart review. Result: 47 patients received more than one allogeneic HCT (second HCT, n=44, second and third HCT, n=3). Median age of the patients was 40 (range, 18–65) years. 27 patients were male, 20 female. Diagnoses were acute myeloid leukemia (n=28), acute lymphoblastic leukemia (n=11), multiple myeloma (n=1), chronic myeloid leukemia (n=2), myelodysplastic syndrome (n=2), osteomyelofibrosis (n=2) and non-Hodgkin lymphoma (n=1). Reasons for second or third HCT were relapse (n=49) or primary graft failure (n=1). Median time between first and second HCT was 17 (range, 3–137) months, 12 months between second and third HCT (range, 10–16). For the first HCT 35 patients received myeloablative (MAC) and 12 reduced intensity conditioning (RIC). For the second HCT 16 patients received MAC and 31 RIC, for the third HCT RIC was used in all patients. 6/47 patients (13%) received salvage chemotherapy followed by RIC out of aplasia. Before salvage HCT disease status of the patients was CR=14, PR=33. Time to neutrophil engraftment after second and third HCT was 16 (range, 6–77) and 10 (range, 9–13) days, respectively; to platelet engraftment 16 (range, 9–71) and 23 (range, 14–73) days, respectively. 12 of 47 patients (26%) after second HCT are alive (CR=11, PR=1) and 1 of 3 patients is alive and in remission after receiving a third HCT. Kaplan-Meier estimated 3-year overall and event-free survival is 30% and 25%, respectively, with a median follow-up of 62 (range 6–111) months of patients alive. Outcome was better for patients in CR at HCT (3-year OS with 43% vs. 24%, p=0.13). In the subgroup of patients with acute leukemia 3-year OS and EFS was superior in patients with AML (32% and 31%) while all patients with ALL died. Older age had no negative impact on survival as 3-year OS in patients ≥40 years (n=25) was 43% compared to 15% in patients <40 years (n=22) (p=0.04). Cumulative incidence of NRM at 3 years with death due to relapse as competing risk after second HCT was 43%. 2 of 3 patients after third HCT died due to NRM. The use of RIC was associated with an inferior 3-year OS compared to MAC with 18% vs. 53%, p=0.08. Causes of death were relapse=18, infection=12, multiorgan failure=3, GVHD=1, EBV-LPD=1 and PML=2. Outcome was inferior if the second HCT was performed within 6 months after first HCT with a 3-year OS of 0% vs. 31%, p=0.02. In 8 patients the same donor as for primary HCT was used while in 39 patients an alternative donor (MRD=7, MUD=10, MMUD=7, MMRD=2, haplo=21) was chosen. Using the same donor seems to result in a better outcome with 3-year OS of 63% vs. 23%, p=0.08. Incidence of grade II-IV GVHD was 17%, of chronic GVHD 30%. Presence of cGVHD after second allogeneic HCT was associated with better survival (3-year OS 42% vs. 26%, p=0.31) especially after using RIC (33% vs. 11%, p=0.09) Conclusion: In view of the otherwise dismal prognosis of patients with relapse after allogeneic HCT, second or third allogeneic HCT is feasible and can achieve long term disease free survival in up to a third of patients, even in patients of more than 40 years of age. Thus, retreatment with allogeneic HCT appears to be the most promising salvage strategy besides DLI for relapse >6 months after allogeneic HCT. Disclosures: Off Label Use: The use of some agents in the conditioning is off-label.

Effect of Interventions for Relapse or Progression Following Allogeneic Hematopoietic Cell Transplantation: A Single-Center Experience of 93 Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1648-1648
Author(s):  
Saiko Kurosawa ◽  
Takahiro Fukuda ◽  
Shin-ichiro Mori ◽  
Sung-Won Kim ◽  
Shigeo Fuji ◽  
...  
Keyword(s):  
Disease Progression ◽  
Cell Transplantation ◽  
Induction Chemotherapy ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct ◽  
Systemic Relapse ◽  
Reduced Intensity

Abstract Background: Relapse/progression after allogeneic hematopoietic cell transplantation (HCT) remains the major cause of treatment failure. In this study, the subsequent clinical outcome in a modern transplant setting was overviewed to improve decision-making. Patients and immediate therapy: Between 2000 and 2006, 294 patients with leukemia/MDS received allogeneic HCT after myeloablative (n=145) or reduced-intensity (n=149) conditioning. Among them, 93 patients (32%) either relapsed or showed disease progression; the relapse rate was 40% for AML (57/144 patients), 18% for MDS (13/72), 14% for CML (5/35), and 42% for ALL (18/43). The median overall survival (OS) after relapse or progression was 167 days (range; 5 to 1456 days). Twenty-eight patients (30%) were elected to receive no interventions with curative intent other than withdrawal of immunosuppressant, less-intensive chemotherapy or DLI, mostly due to comorbidities or refractoriness of the disease, and all but 3 patients died with disease progression at a median of 61 days. Two other patients underwent immediate HCT without intervention due to graft failure. Among the remaining 63 patients (68%) who received therapeutic interventions including re-induction chemotherapy with or without DLI, 26 (41%) achieved subsequent complete remission (CR). Salvage transplantation: Forty-five patients (15 in CR and 30 in non-CR) did not undergo a second HCT due to various reasons including progressive disease (n=28), infection (n=6), GVHD (n=3), refusal (n=3), and rather stable disease (n=5). Overall, 20 patients underwent salvage HCT using myeloablative (n=8) or reduced-intensity (n=12) conditioning: 11 in CR and 9 in non-CR. The incidence of TRM after the second HCT was not remarkable (5%). The probability of achieving CR after the second HCT was 75%, compared to 35% after other interventions (p=0.001), and the 1-year OS after relapse was significantly better in patients with the second HCT than that in others (58% vs 14%, p&lt;0.0001), but these favorable outcomes may simply reflect the patient-selection bias. The 2-year OS did not differ between the two groups, which suggests that it is difficult to maintain CR after a second HCT. Currently, 15 of the 93 patients (16%) are alive with a median follow-up of 346 days (range; 33 to 1456 days), and 10 of these patients are still in CR. Notably, 5 patients are alive in CR without a second HCT: 3 suffered from central nervous system relapse without systemic relapse and received localized therapy alone (follow-up; 494 to 1456 days), and the remaining 2 have had a rather short follow-up after DLI. Multivariate analysis showed that re-induction chemotherapy, CR after intervention, a second HCT, and a longer time to post-transplantation relapse (≥100 days) were associated with improved OS after relapse. Conclusion: For patients with chemosensitive systemic relapse, a second allogeneic HCT may improve survival and could be considered as an effective therapeutic option. Figure Figure

Relapse of Lymphoma After Allogeneic Hematopoietic Cell Transplantation: Management Strategies and Outcome.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4503-4503
Author(s):  
Kitsada Wudhikarn ◽  
Qing Cao ◽  
Claudio Brunstein ◽  
Veronika Bachanova ◽  
Linda J Burns ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Stable Disease ◽  
Hodgkin’S Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Management Strategies ◽  
Donor Lymphocyte Infusion ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Hodgkin's Lymphoma ◽  
Allogeneic Hct

Abstract Abstract 4503 Background&Objective: The management of lymphoma which has relapsed after allogeneic hematopoietic cell transplantation (HCT) is difficult. Therapeutic options may include donor lymphocyte infusion (DLI), withdrawal of immunosuppression, rituximab, chemotherapy, radiation, immunotherapy and experimental treatments, but response and survival are uncertain. Result: We analyzed 72 patients with relapsed or progressive lymphoma after allogeneic HCT (1991-2007); 44 non-Hodgkin's lymphoma (7 mantle cell, 5 indolent, 19 diffuse large B [DLBCL], and 13 T/NK cell) and 28 Hodgkin's lymphoma (HL). At HCT, 62 patients (86%) were in remission (22 CR, 40 PR); nine (13%) had progressive disease and one had stable disease. Conditioning was myeloablative (n=17) or reduced intensity conditioning (RIC) (n=55). Relapse or progression occurred at a median of 99 days (0-1898 days; 25–75% 43–194 days). At relapse, 41 (57%) had extensive nodal disease and 56 (78%) had extranodal organ involvement. Management of relapse included: no therapy (n=5, 7%), reduction of immunosuppression (RIS) (n=58, 81%), chemotherapy alone (n=14, 19%), immunotherapy alone (n=20, 28%), combined chemo-immunotherapy (n=7, 10%) donor lymphocyte infusion (DLI) (n=7, 10%), second allogeneic HCT (n=2, 3%), radiation (n=23, 32%) and other therapy (n=7, 8%). Twenty-four patients achieved a remission (15 CR, 9 PR) to the initial salvage therapy: RIS (n=13), combined chemo-immunotherapy(n=5), chemotherapy alone (n=2), radiation (n=3) or DLI (n=1). Overall, 40 (56%) patients responded (30 CR, 8 PR, 2 stable disease) with a median post-relapse overall survival of 28 months (range 0–147 months). At 3 years following relapse, 44% (95% CI, 32–56%) survive. Favorable prognostic factors for improved 3-year survival after relapse include stage I-III at relapse, single site of relapse and most importantly, later relapse (>100 days after HCT [3 year survival 53% vs. 36%, p=0.02]). Conclusion: The overall prognosis of relapsed lymphoma after allogeneic HCT differs based upon extent of disease at relapse and time of relapse. Appropriate therapeutic approaches (RIS, combined chemo-immunotherapy, radiation or DLI) in these high risk, post transplant relapsed patients can yield promising outcome. Prospective study of post-relapse therapy to determine the most effective management strategies are warranted. Disclosures: No relevant conflicts of interest to declare.

High dose valacyclovir for cytomegalovirus prophylaxis following allogeneic hematopoietic cell transplantation

2021 ◽  
pp. 107815522110604
Author(s):  
Kelly G Hawks ◽  
Amanda Fegley ◽  
Roy T Sabo ◽  
Catherine H Roberts ◽  
Amir A Toor
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Cmv Infection ◽  
Allogeneic Hct ◽  
Clinically Significant ◽  
Cmv Disease ◽  
Cmv Prophylaxis

Introduction Cytomegalovirus (CMV) is one of the most common and clinically significant viral infections following allogeneic hematopoietic cell transplantation (HCT). Currently available options for CMV prophylaxis and treatment present challenges related to side effects and cost. Methods In this retrospective medical record review, the incidence of clinically significant CMV infection (CMV disease or reactivation requiring preemptive treatment) following allogeneic HCT was compared in patients receiving valacyclovir 1 g three times daily versus acyclovir 400 mg every 12 h for viral prophylaxis. Results Forty-five patients who received valacyclovir were matched based on propensity scoring to 35 patients who received acyclovir. All patients received reduced-intensity conditioning regimens containing anti-thymocyte globulin. Clinically significant CMV infection by day + 180 was lower in the valacyclovir group compared to the acyclovir group (18% vs. 57%, p = 0.0004). Patients receiving valacyclovir prophylaxis also had less severe infection evidenced by a reduction in CMV disease, lower peak CMV titers, delayed CMV reactivation, and less secondary neutropenia. Conclusion Prospective evaluation of valacyclovir 1 g three times daily for viral prophylaxis following allogeneic HCT is warranted. Due to valacyclovir's favorable toxicity profile and affordable cost, it has the potential to benefit patients on a broad scale as an option for CMV prophylaxis.

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