Haploidentical Transplantation As Salvage Therapy For Disease Relapse After Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2084-2084
Author(s):  
Christiane Dorn ◽  
Sebastian P. Haen ◽  
Christoph Faul ◽  
Wichard Vogel ◽  
Lothar Kanz ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Median Time ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
The Other ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct

Abstract Introduction Therapeutic options and outcome for patients with relapse after allogeneic hematopoietic cell transplantation (HCT) are poor. For individual patients, a second or even third allogeneic HCT can be considered with curative intention. However, treatment-related mortality (TRM) and the risk of relapse after secondary allogeneic HCT are high. Therefore, the use of a haploidentical graft allowing for profound NK- and T-cell-alloreactivity after a reduced-intensity conditioning regimen (RIC) may optimize disease control by enabling potent graft versus leukemia effects and reduction of TRM. Methods We here retrospectively evaluated 26 consecutive patients undergoing haploidentical HCT as second (n=24) or third (n=2) allogeneic HCT at our center between 2003-2012. Diagnoses comprised relapse of AML (n=17) or ALL (n=7), blast crisis of CML (n=1) and transplant failure (n=1). There were 16 male and 9 female patients with a median age of 36 years (range 18-59). Results For RIC, fludarabin, thiotepa and melphalan were used in 16 patients, clofarabin, thiotepa and melphalan in 6 patients and other regimens containing variable combinations of cyclophosphamide, busulfan, TBI and treosulfan in 4 patients. Grafts were manipulated by CD3/CD19 depletion (n=19), TCRαβ depletion (n=1) or CD34 selection (n=6) and consisted of a median of 7.71 x 106 CD34+cells/kg bodyweight. The median interval from first HCT to second HCT was 18 months (range 5-145), and 10 and 16 months from second HCT to third HCT in the two patients undergoing a third HCT. Only 35% (n=9) of the patients receiving a second HCT were in complete remission (CR), while 65% (n=16) were in partial remission (PR). Among the patients receiving a third HCT, one had active disease, while the other was in CR. All patients achieved engraftment of the neutrophils at a median time of 11 days (range 8-26) and platelet engraftment was reached at a median time of 15 days (range 9-35, except one patient at day 375). At present, 5 patients (19%) are alive and in CR with a median follow-up of 1870 days (range 281-3941), while 35% (n=9) died from relapse; non-relapse-mortality was 46% (n=12). Kaplan-Meier estimated overall survival for all patients at 1 year was 33% (52% for patients in CR versus 18% in PR) and at 3 years 17% (26% for patients in CR versus 12% in PR). Causes of death in patients with second HCT included severe infections (n=8), organ failure (n=1), haemorrhage (n=1) and progressive multifocal leukoencephalopathy (n=2). Of the patients with third HCT, one died from respiratory insufficiency due to pulmonary haemorrhage, the other is still alive and in CR. Acute graft versus host disease (GVHD) occurred in 11 patients with predominantly mild presentation (grade 1: n=9, grade 2: n=2), limited chronic GVHD was apparent in 5 patients with no case of extensive GVHD. Conclusion Haploidentical HCT is a feasible salvage concept for patients with relapse after HCT with promising results even in patients not in CR. Disclosures: No relevant conflicts of interest to declare.

The Effect of In Vivo T-Cell Depletion with Alemtuzumab on Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3014-3014
Author(s):  
Julio Delgado ◽  
Srinivas Pillai ◽  
Reuben Benjamin ◽  
Dolores Caballero ◽  
Rodrigo Martino ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Mixed Chimerism ◽  
Allogeneic Hct ◽  
Reduced Intensity

Abstract Reduced-intensity allogeneic hematopoietic cell transplantation (HCT) is increasingly considered as a therapeutic option for young patients with advanced chronic lymphocytic leukemia (CLL). We report 59 consecutive CLL patients who underwent allogeneic HCT following fludarabine and melphalan conditioning at four different institutions. For graft-versus-host disease (GVHD) prophylaxis, 38 patients (Cohort 1) received alemtuzumab (20–100 mg) and cyclosporine; and 21 patients (Cohort 2) received cyclosporine plus methotrexate or mycophenolate. Donors were 47 HLA-matched siblings and 12 unrelated volunteers, 6 of whom were mismatched. Median age at transplant was 53 (range, 34–64) years and median number of previous chemotherapy regimens was 3 (1–6), with 39% of patients being refractory to fludarabine. Nine patients had previously failed an autologous HCT. Fluorescent in-situ hybridization and IgVH mutation status data were available in 33 (56%) and 31 (53%) patients, respectively, being unfavorable (17p- or 11q-) in 22 (67%) and unmutated in 24 (77%) of them. All but 1 patient engrafted, and the median interval to neutrophil recovery (> 0.5 × 109/l) was 14 (range, 10–36) days. Twenty patients (34%), mostly from Cohort 1, received escalated donor lymphocyte infusions due to mixed chimerism or disease relapse. The overall complete response rate among 53 patients with measurable disease at the time of transplantation was 70%, whereas 21% had stable disease. Grade II-IV acute GVHD was observed in 14 (37%) and 12 (57%) patients from Cohorts 1 and 2, respectively (P = 0.17). Extensive chronic GVHD was observed in 3 (8%) and 10 (48%) patients from Cohorts 1 and 2, respectively (P < 0.01). The incidence of cytomegalovirus reactivation was not significantly different between cohorts (67% vs 47%, P = 0.23). With a median follow-up of 36 (range, 3–99) months for survivors, 18 (30%) patients have died, 3 of progressive disease and 15 of transplant-related complications. The 3-year overall survival (OS), progression-free survival (PFS) and non-relapse mortality were 66% (95% CI 48–84%), 38% (20–56%) and 21% (8–34%), respectively, for Cohort 1 and 65% (44–86%), 54% (32–76%) and 29% (10–48%) for Cohort 2 (P = 0.66; P = 0.33; and P = 0.53). Despite low patient numbers, alemtuzumab seemed particularly effective for unrelated donor recipients, with a 3-year OS and PFS of 54% and 40% for Cohort 1; and 33% and 0% for Cohort 2 (P = 0.02 and P = 0.07). In conclusion, results with reduced-intensity allogeneic HCT are promising for these poor-prognosis patients. Furthermore, the alemtuzumab-based regimen was effective in reducing the chronic GVHD rate with no negative effect on NRM, PFS or OS.

Allogeneic Hematopoietic Cell Transplantation (allo-HCT) Can Induce Durable Remission in Heavily Pretreated Relapsed Hodgkin Lymphoma. (HL).

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1192-1192
Author(s):  
Robert Chen ◽  
Joycelynne Palmer ◽  
Leslie Popplewell ◽  
Jessica Shen ◽  
Eileen Smith ◽  
...  
Keyword(s):  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Unrelated Donor ◽  
Heavily Pretreated

Abstract Abstract 1192 Poster Board I-214 Background: Even though Hodgkin lymphoma (HL) is a curable disease, about, 20-30% patients are either refractory to induction chemotherapy or relapse post treatment. High dose chemotherapy and autologous HCT has been shown to be an effective salvage therapy for patients with relapsed HL. However, relapse continues to occur after auto-HCT, especially in patients with chemoresistant or poor-risk features at relapse. The prognosis of these patients is poor with limited options of treatment. Although allo-HCT offers both cytoreduction and potential graft-versus-tumor effect, its use in relapsed HL has been limited by non-relapse mortality (NRM) and patient co-morbidities induced by numerous prior treatments. To examine the potential impact of allo-HCT on survival and disease outcomes, we performed retrospective analysis of allo-HCT in relapsed/refractory HL to determine if allo-HCT can induce long-term remission in heavily pretreated relapsed HL. Results: Between January 2003 and December 2008, 29 patients with relapsed HL underwent allo-HCT at City of Hope National Medical Center. The median age was 37 (range: 14-63). 20 (69%) patients were chemosensitive at time of allo-HCT. 17 (59%) patients had prior auto-HCT. 16 (55%) patients received matched siblings and 13 (45%) received unrelated donor cells. 20 (69%) patients had prior radiation treatments. The median number of prior regimens was 5 (range: 2-8). 23 (79%) patients underwent a non-myeloablative conditioning regimen while 6 (21%) patients had a myeloablative regimen. 14 (48%) patients received Tacrolimus/Sirolimus as graft versus host disease prophylaxis and 15 (52%) patients received a combination of Cellcept/CsA, Cellcept/CsA/MTX, Tacrolimus/MTX, or Tacrolimus/Sirolimus/MTX. With a median follow up of 31.9 months (range: 9.7-69.1) for surviving patients, the results show: Conclusion: Allogeneic hematopoietic cell transplantation in heavily pretreated relapsed Hodgkin's lymphoma is feasible, tolerable, and can induce durable clinical remissions. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Nonmyeloablative Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia

2010 ◽  
Vol 28 (17) ◽  
pp. 2859-2867 ◽  
Author(s):  
Boglarka Gyurkocza ◽  
Rainer Storb ◽  
Barry E. Storer ◽  
Thomas R. Chauncey ◽  
Thoralf Lange ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Cell Transplantation ◽  
Myeloid Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Allogeneic Hct ◽  
Unrelated Donors ◽  
Acute Myeloid

PurposeAllogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning regimens imposes prohibitively high risks of morbidity and mortality for patients with high-risk acute myeloid leukemia (AML) who are older or have comorbid conditions. Here, we examined outcomes after nonmyeloablative allogeneic HCT in such patients.Patients and MethodsTwo hundred seventy-four patients (median age, 60 years) with de novo or secondary AML underwent allogeneic HCT from related (n = 118) or unrelated donors (n = 156) after conditioning with 2 Gy of total-body irradiation (TBI) with or without fludarabine. A calcineurin inhibitor and mycophenolate mofetil were used for postgrafting immunosuppression.ResultsWith a median follow-up of 38 months in surviving patients, the estimated overall survival at 5 years was 33%. The estimated 5-year relapse/progression and nonrelapse mortality rates were 42% and 26%, respectively. The cumulative incidences of grades 2, 3, and 4 acute graft-versus-host disease (GVHD) were 38%, 9%, and 5%, respectively. The cumulative incidence of chronic GVHD at 5 years was 44%. Patients in first and second complete remission had better survival rates than patients with more advanced disease (37% and 34% v 18%, respectively). Patients with HLA-matched related or unrelated donors had similar survivals. Unfavorable cytogenetic risk status was associated with increased relapse and subsequent mortality. Chronic GVHD was associated with lower relapse risk.ConclusionAllogeneic HCT from related or unrelated donors after conditioning with low-dose TBI and fludarabine, relying almost exclusively on graft-versus-leukemia effects, can result in long-term remissions in older or medically infirm patients with AML.

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.

Patterns of Acute and Chronic Graft-Versus-Host Disease Following ATG-Based Conditioning for Allogeneic Hematopoietic Cell Transplantation

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4479-4479
Author(s):  
Nandita Khera ◽  
Amylou C. Dueck ◽  
Veena Devi Salem Fauble ◽  
Lisa Sproat ◽  
Pierre Noel ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Median Time ◽  
Cumulative Incidence ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Median Number ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Grade Ii

Abstract Abstract 4479 Background: In vivo T-cell depletion with antithymocyte globulin (ATG) is known to decrease the incidence of acute and chronic graft vs. host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT). However, the detailed patterns of GVHD (incidence, severity, timing, and quality) after ATG-based conditioning have not been examined in large patient cohorts, and it is unknown whether they differ from those seen in patients who do not receive ATG during conditioning therapy. Patients and Methods: We analyzed the incidence and characteristics of acute and chronic GVHD, requirements for immunosuppressive therapy (IST) and survival in a cohort of 174 patients who underwent a first HCT for hematologic malignancy with ATG as a part of their conditioning regimen. The median age was 54 years (range 19–76); all but 5 pts received PBSC, and median follow-up of survivors was 16.9 months (range 3–70 months). Donors were matched related in 18% (n=32), matched unrelated in 44% (n=77), and mismatched unrelated in 37% (n=65). Conditioning regimens were myeloablative in 33% (n=57) and reduced intensity in 67% (n=117). Additional GVHD prophylaxis included tacrolimus in all patients combined with either methotrexate (42%) or MMF (58%). Results: The cumulative incidence of grade II-IV and III-IV acute GVHD at 100 days was 34% and 7%, respectively, with the median time of onset at 43 days (range 11–98 days) after transplant. Eleven patients (6.3%) required additional immunosuppressive treatment due to steroid refractory GVHD. Late/persistent acute GVHD without any evidence of chronic occurred in 25% of patients. NIH chronic GVHD developed in 25 patients, with a cumulative incidence of 24.4% at 2 years. Forty four percent of these patients were classified as classic chronic, and 56% as overlap. The onset of chronic GVHD was quiescent in 20 (80%), progressive in 3 (12%), and de-novo in 2 (8%) patients. The global severity was mild in 9 (36%), moderate in 11 (44%) and severe in 5 (20%) cases. The median time of onset for chronic GVHD was 185 days (range 99–763). In a multivariate analysis of factors predictive for development of chronic GVHD, the only factor associated with development of chronic GVHD was prior grade II-IV acute GVHD (HR 2.5, p =.03). The most common diagnostic organ was mouth (n=16), followed by skin (n=8) and eye (n=1). The median number of sites involved during the course of chronic GVHD was 4 (range 1–7), and the median number of systemic immunosuppressive agents for treatment was 2 (range 0–4). Among the 25 chronic GVHD patients, 5 have discontinued immunosuppression at a median time of 13.1 months (range 6–26) since the diagnosis of chronic GVHD. The cumulative incidence of discontinuation of IST was 23% at one year and 50% at two years. Three deaths in the overall cohort were attributed to complications related to acute (n=2) or chronic GVHD (n=1). At 2 years, the overall survival among all 174 pts was 62.4%, cumulative incidence of relapse was 23.1%, and non-relapse mortality was 22.7%. Conclusion: These data from a large, uniformly treated and graded, predominantly peripheral blood stem cell transplant recipient population, confirm that ATG decreases both the incidence and severity of acute and chronic GVHD. In particular, the rate of moderate to severe chronic GVHD is extremely low, resulting in minimal need for tertiary treatment and decreased duration of immunosupression. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Consolidation Chemotherapy Is Not Beneficial for Adult Acute Lymphoblastic Leukemia Patients with Available Donor Undergoing Myeloablative Allogeneic Hematopoietic Cell Transplantation in First Complete Remission: A CIBMTR Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 684-684
Author(s):  
Nelli Bejanyan ◽  
Aleksandr Lazaryan ◽  
Mei-Jie Zhang ◽  
Hai-Lin Wang ◽  
Marcos de Lima ◽  
...  
Keyword(s):  
Complete Remission ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Consolidation Chemotherapy ◽  
P Values

Abstract Allogeneic hematopoietic cell transplantation (alloHCT) is potentially curative for patients with ALL who achieve complete remission with upfront chemotherapy (CR1). However, the necessity of consolidation chemotherapy remains uncertain in patients with an available donor undergoing alloHCT, even if the goal is to reduce the detectable disease burden prior to alloHCT. We therefore compared clinical outcomes of 524 adult patients with ALL in CR1 who received ≥2 cycles (n=109) vs. 1 cycle (n=93) vs. no (n=322) consolidation chemotherapy prior to myeloabalative alloHCT from 2008-2012. The median follow up of survivors was 59 (6-78) months. All three consolidation groups had similar patient, disease and transplant characteristics, but no consolidation patients were older, took longer to achieve CR1 and less frequently received CNS prophylaxis or maintenance chemotherapy prior to alloHCT. In contrast, fewer with 1 cycle consolidation had prior comorbidities. Time to alloHCT was longer with increasing cycles of consolidation. Only a minority had either cytogenetic or molecular detectable disease in their pre-HCT CR1 assessment; and it was similar in each consolidation cohort. For ≥2 cycles, 1-cycle, no consolidation groups, the adjusted 3-year cumulative incidence of relapse was 20%, 27% and 22% and 1-year transplant-related mortality (TRM) was 16%, 18% and 23%, respectively (all p-values > 0.4). Similarly, adjusted 3-year leukemia-free survival (LFS) was 54%, 48% and 47% (Figure), while overall survival (OS) was 63%, 59% and 54%, respectively (all p-values > 0.3). Consolidation did not influence acute or chronic GVHD risks. Multivariable regression analysis adjusted for recipient age, Karnofsky performance status, time to CR1, graft source, donor type and recipient CMV serostatus, confirmed that consolidation chemotherapy was not prognostic of LFS (RR=1.20, 95% CI 0.86-1.67; p=0.28 for no consolidation; RR=1.18, 95% CI 0.79-1.76; p=0.41 for 1 cycle; ≥2 cycles=reference). Similarly, consolidation was not associated with OS, relapse, TRM or GVHD. We conclude that consolidation chemotherapy does not benefit adult ALL patients with readily available donor who undergo myeloablative alloHCT in CR1. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

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.

scholarly journals Ruxolitinib Therapy during Hematopoietic Cell Transplantation for Myelofibrosis

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1795-1795
Author(s):  
Yaxian Tan ◽  
Jie Luo ◽  
Dongmei Luo ◽  
Hanying Liang ◽  
Xiaoli Liu ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Median Time ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Myeloproliferative Neoplasms ◽  
Chronic Gvhd ◽  
Graft Function ◽  
Hematopoietic Cell ◽  
World Health ◽  
Conditioning Treatment

Abstract Background :The beneficial effects of JAK 1/2 inhibitors (JAKi) ruxolitinib in MF patients have led to control of disease related symptoms,but ruxolitinib has been limited by their inability to deplete the malignant stem cell clones. Allogeneic hematopoietic cell transplantation (HCT) is currently the only treatment with proven curative potential for myelofibrosis (MF). Previous research suggested pre-HCT ruxolitinib may improve post-HCT outcome because of ruxolitinib accelerate engraftment, improve graft function, decrease the risk and severity of graft-versus-host disease (GVHD). However,HCT in PMF with higher non-relapse mortality (NRM),In the present study, we aimed to prospectively assess the effects of Rux therapy during HCT period(NCT04526223). Objective Preliminarily investigate the safety and efficacy of ruxolitinib in myelofibrosis patients during the peri-transplantation period. Method: To prospectively analyze the clinical data of 26 patients with myelofibrosis who were used DAC bridge BF as conditioning treatment and treated with ruxolitinib(5mg bid +6d to +60d) during the peri-transplantation period. Results: 26 patients were eligible if they had primary myelofibrosis (PMF) as defined by the 2008 World Health Organization classification or secondary MF as defined by the IWG for Myeloproliferative Neoplasms Research and Treatment criteria and met the criteria for Intermediate-1 (Int-1), Int-2, or high-risk disease by the DIPSS scoring system at the time of enrollment. Patients consenting to treatment with Rux for at least 8 weeks prior to HCT and could receive Rux (5mg bid +6d to +60d) during the peri-transplantation period. DAC bridge BF as Myeloablative regiment, There have been no episodes of cytokine release syndrome and all patients achieved sustained engraftment. Neutrophil reconstitution was obtained in 26 patients with a median time of 15 (10 to 31) d; platelet reconstitution was obtained in 26 patients with a median time of 26(12 to 68) d. Acute GVHD occurred in 26 patients (46.15%) , of which 1(3.8%) were ш°; chronic GVHD occurred in 9 patients (34.6%), 1 patients with extensive chronic GVHD. There patients relapsed and two patients died because of resistance to alvage treatment . With a median follow-up 336 (70-993) days，no patient died of non-relapse mortality (NRM)., overall survival is 92.3% (95% CI: 0.73, 0.97) and DFS is 88.5% (95% CI: 0.63, 0.96) at1 year post-HCT. Conclusion: This study demonstrates that Ruxolitinib therapy during HCT is well tolerated and suggests that during-HCT Rux may improve post-HCT outcome. Keywords: Ruxolitinib;Hematopoietic Cell Transplantation;Myelofibrosis Disclosures No relevant conflicts of interest to declare.

scholarly journals Graft-Versus-Host Disease and Graft-Versus-Tumor Effects After Allogeneic Hematopoietic Cell Transplantation

2013 ◽  
Vol 31 (12) ◽  
pp. 1530-1538 ◽  
Author(s):  
Rainer Storb ◽  
Boglarka Gyurkocza ◽  
Barry E. Storer ◽  
Mohamed L. Sorror ◽  
Karl Blume ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
High Dose ◽  
Host Disease ◽  
Graft Versus Host

Purpose We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graft-versus-host disease (GVHD) not augmented by regimen-related toxicities. Patients and Methods Patients received low-dose total-body irradiation ± fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of ≥ 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years). Results Depending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM. Conclusion Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD.

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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