scholarly journals Impact of Chronic GVHD on Late Relapse, Treatment Related Mortality and Survival After Allogeneic Hematopoietic Cell Transplantation for Hematological Malignancies

2012 ◽  
Vol 18 (2) ◽  
pp. S209-S210
Author(s):  
M. Boyiadzis ◽  
J.P. Klein ◽  
M. Arora ◽  
D.J. Weisdorf ◽  
A. Hassebroek ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Late Relapse ◽  
Relapse Treatment ◽  
Treatment Related Mortality ◽  
Related Mortality

Comparable Survival and Transplant-Related Mortality Following Allogeneic Hematopoietic Cell Transplantation from HLA Allele-Matched Unrelated and HLA-Identical Sibling Donors.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3146-3146 ◽  
Author(s):  
Thai M. Cao ◽  
Schickwann Tsai ◽  
Linda Kelley ◽  
Stephen C. Alder ◽  
Thomas C. Fuller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cell Transplantation ◽  
Acute Gvhd ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
P Value ◽  
Unrelated Donor ◽  
Related Mortality

Abstract Comprehensive analyses of unrelated donor (URD) and recipient HLA-matching for allogeneic hematopoietic cell transplantation (AHCT) have demonstrated better outcomes when allele typing is performed using high-resolution nucleotide sequence-based techniques. To evaluate survival following myeloablative AHCT using allele-level HLA-matched URD as compared with HLA-identical sibling donors, we analyzed outcomes for 430 patients treated at our center between March 1991 and April 2005. Sequence-based allele typing was retrospectively performed for HLA-A, B, C, DR and DQ when not done at time of AHCT for URD (n = 124; 29%) and non-sibling related donors (n = 19; 4%). Donors were HLA-identical siblings (n = 276; 64%), HLA allele-matched URD (n = 52; 12%), single HLA-locus mismatched donors (n = 52; 12%), or > 1 locus mismatched donors (n = 50; 12%). The median age at transplant was 23.4 years (range: 0.2 – 61). The most common diagnoses were AML (n = 107; 25%), CML (n = 90; 21%), ALL (n = 86; 20%) and MDS (n = 50; 12%). Total body irradiation-based preparative regimens were used for 283 patients (66%). Bone marrow (BM) was the graft for 388 patients (90%) and GCSF-mobilized peripheral blood stem cells (PBSC) for the remaining 42 (10%). Graft-versus-host disease (GVHD) prophylaxes were cyclosporine and methotrexate (n = 327; 76%), long methotrexate (n = 42; 10%), T-cell depletion (n = 19; 4%), or other regimens (n = 42; 10%). With a median follow-up of 4.8 years (range: 0.2 – 12.1), the 5-year estimate of overall survival (OS) for the entire group was 48.2% (95% CI: 45.7 – 50.7) and transplant-related mortality (TRM) was 31.4% (95% CI: 28.8 – 34). As shown in the Table, OS and TRM were indistinguishable between AHCT performed with HLA-identical siblings compared with HLA allele-matched URD. There was also no difference in grade III – IV acute GVHD (P = .46) between these two groups whereas there was a trend towards more extensive chronic GVHD (HR 1.8; 95% CI: 0.9 – 3.6; P = 0.12) for the URD recipients. Using a multivariate analysis to adjust for advanced disease, age (> vs ≤ 30 years), graft (BM vs PBSC) and female-to-male gender mismatch, there remained no difference in OS between HLA-identical siblings and HLA allele-matched URD (P = 0.67). These results demonstrate that key outcomes (OS, TRM, and severe acute GVHD) are equivalent in recipients of grafts from either allele-level 10/10 HLA-matched URD or HLA-identical siblings. Overall Survival TRM Number Hazard Ratio 95% CI P value Hazard Ratio95% CI P value HLA-ID Sibling 276 1 - - 1 - - HLA-ID URD 52 1.1 0.7 – 1.7 0.67 0.8 0.4 – 1.6 0.58 1 Locus MM 52 1.3 0.9 – 2.0 0.19 1.4 0.8 – 2.4 0.25 > 1 Locus MM 50 2.0 1.4 – 2.9 < 0.001 2.6 1.7 – 4.1 < 0.001

scholarly journals Trends in allogeneic stem cell transplantation for multiple myeloma: a CIBMTR analysis

Blood ◽  
2011 ◽  
Vol 118 (7) ◽  
pp. 1979-1988 ◽  
Author(s):  
Shaji Kumar ◽  
Mei-Jie Zhang ◽  
Peigang Li ◽  
Angela Dispenzieri ◽  
Gustavo A. Milone ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Recent Cohort ◽  
Over Time ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Allogeneic hematopoietic cell transplantation in multiple myeloma is limited by prior reports of high treatment-related mortality. We analyzed outcomes after allogeneic hematopoietic cell transplantation for multiple myeloma in 1207 recipients in 3 cohorts based on the year of transplantation: 1989-1994 (n = 343), 1995-2000 (n = 376), and 2001-2005 (n = 488). The most recent cohort was significantly older (53% > 50 years) and had more recipients after prior autotransplantation. Use of unrelated donors, reduced-intensity conditioning and the blood cell grafts increased over time. Rates of acute graft-versus-host (GVHD) were similar, but chronic GVHD rates were highest in the most recent cohort. Overall survival (OS) at 1-year increased over time, reflecting a decrease in treatment-related mortality, but 5-year relapse rates increased from 39% (95% confidence interval [CI], 33%-44%) in 1989-1994 to 58% (95% CI, 51%-64%; P < .001) in the 2001-2005 cohort. Projected 5-year progression-free survival and OS are 14% (95% CI, 9%-20%) and 29% (95% CI, 23%-35%), respectively, in the latest cohort. Increasing age, longer interval from diagnosis to transplantation, and unrelated donor grafts adversely affected OS in multivariate analysis. Survival at 5 years for subjects with none, 1, 2, or 3 of these risk factors were 41% (range, 36%-47%), 32% (range, 27%-37%), 25% (range, 19%-31%), and 3% (range, 0%-11%), respectively (P < .0001).

Late Relapse After Allogeneic Hematopoietic Cell Transplantation For Hematological Malignancies: A Nationwide Retrospective Study From The Late Complications and Quality-Of-Life Working Group Of The Japan Society For Hematopoietic Cell Transplantation

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4630-4630
Author(s):  
Takuya Yamashita ◽  
Hideyuki Kuwabara ◽  
Kazuteru Ohashi ◽  
Naoyuki Uchida ◽  
Takahiro Fukuda ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematological Malignancies ◽  
Hematopoietic Cell Transplantation ◽  
Disease Risk ◽  
Chronic Gvhd ◽  
Hematopoietic Cell ◽  
Late Relapse ◽  
Unrelated Donor ◽  
Conditioning Regimens ◽  
Related Donor

Background Allogeneic hematopoietic cell transplantation (HCT) is one of the most curative therapeutic modalities for hematological malignancies. Recent advances in availability of stem cell sources, conditioning regimens, managements of graft-versus-host disease (GVHD) and supportive care have improved the outcomes of HCT. But even now, relapse is still the leading cause of treatment failure and some long-term survivors after HCT suffer late relapse of the original disease. To better understand the risk and risk factors of late relapse in HCT recipients, we conducted a nationwide retrospective study of the patients who received first HCT for hematological malignancies in Japan. Patients and Methods The study population included HCT recipients reported to the Japan Society for Hematopoietic Cell Transplantation. From this database, we extracted the data of patients with hematological malignancies who received first HCT between 1974 and 2011. There were 29,479 recipients selected according to this criterion. Then, we excluded 1,192 (4.0%) cases from the study because of missing key variables. Results A total of 28,287 recipients were evaluated in this study. Median age at transplant was 37 years old (range, 0-88), and 41.0% (n=11,605) were female. Underlying diseases were acute lymphoblastic leukemia (ALL) (n=7,300, 25.8%), acute myeloid leukemia (AML) (n=11,526, 40.7%), chronic myelogenous leukemia (CML) (n=3,038, 10.7%), myelodysplastic syndrome (MDS) (n=3,235, 11.4%), malignant lymphoma (ML) (n=2,956, 10.5%) and plasma cell disorder (PCD) (n=232, 0.8%). Type of transplant included bone marrow transplantation (BMT) from HLA-matched or 1 locus serological mismatched (“matched”) related donor (n=8,002, 28.3%), BMT from more than 1 locus-mismatched (“mismatched”) related donor (n=261, 0.9%), BMT from HLA-matched unrelated donor (n=9,074, 32.1%), BMT from HLA-mismatched unrelated donor (n=1,112, 3.9%), peripheral blood stem cell transplantation (PBSCT) from “matched” related donor (n=4,385, 15.5%), PBSCT from “mismatched” related donor (n=467, 1.7%), cord blood transplantation (CBT) from “matched” unrelated donor (n=2,326, 8.2%) and CBT from “mismatched” unrelated donor (n=2,556, 9.0%). Myeloablative conditioning regimens were applied to 77.0% (n=21,773) of recipients and reduced-intensity conditioning regimens to 22.1% (n=6,247). Median follow-up of survivors was 1,934 days (range, 18-11,123). Event-free survival of all cases was 41.8% and cumulative incidence of relapse (RI) of them was 33.1% at 5 years. Disease-free survival (DFS) and RI at 7 years of recipients who had been in remission for 2 years since HCT (“DF2”, n=11,500) were 83.2% and 10.2%. DFS and RI at 10 years of recipients who had been disease-free for 5 years (“DF5”, n=7,093) were 91.5% and 2.9%. In multivariate analysis, disease, disease risk at transplant and patients’ age were powerful (p<1×10-6) significant variables for DFS both of DF2 and DF5. For risk of relapse, disease and disease risk at transplant were powerful (p<1×10-4) significant variables of both DF2 and DF5, but patients’ age and intensity of conditioning regimen were only of DF2. Adjusted for patients’ age, disease risk at transplant, year of transplant, donor-recipient sex match, ABO disparity, type of transplant and intensity of conditioning regimen, acute and chronic GVHD were included as time-dependent covariates in Cox model for relapse. In DF2, grade II-IV acute GVHD was associated with a reduced risk of relapse for patients with ALL (Hazard Ratio 0.75, 95% confidence interval 0.57-0.99, p=0.043) and AML (0.74, 0.57-0.97, p=0.029), and chronic GVHD for those with CML (0.65, 0.47-0.89, p=0.0067) and ML (0.37, 0.20-0.60, p=0.00067). In DF5, grade II-IV acute GVHD significantly reduced risk of relapse for recipients with AML (0.40, 0.18-0.85, p=0.018), and chronic GVHD for those with CML (0.56, 0.34-0.92, p=0.021). Conclusion Recipients of HCT for hematological malignancies who remain in remission for more than 2 or 5 years have favorable long-term survival. Our study demonstrates there are relatively small but persistent risks of relapse and underlying disease and disease risk at transplant are the major risk factors of late relapse. We also show acute and chronic GVHD are associated with a reduced risk of late relapse but the strength of this association differs between underlying diseases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Influence of immunosuppressive treatment on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation

Blood ◽  
2011 ◽  
Vol 118 (2) ◽  
pp. 456-463 ◽  
Author(s):  
Yoshihiro Inamoto ◽  
Mary E. D. Flowers ◽  
Stephanie J. Lee ◽  
Paul A. Carpenter ◽  
Edus H. Warren ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Immunosuppressive Treatment ◽  
Hematopoietic Cell ◽  
Allogeneic Hematopoietic Cell Transplantation ◽  
Study Cohort ◽  
Recurrent Malignancy ◽  
Time Varying Covariates ◽  
Risk Of Relapse

AbstractThis study was conducted to elucidate the influence of immunosuppressive treatment (IST) and GVHD on risk of recurrent malignancy after allogeneic hematopoietic cell transplantation (HCT). The study cohort included 2656 patients who received allogeneic HCT after high-intensity conditioning regimens for treatment of hematologic malignancies. Rates and hazard ratios of relapse and mortality were analyzed according to GVHD and IST as time-varying covariates. Adjusted Cox analyses showed that acute and chronic GVHD were both associated with statistically similar reductions in risk of relapse beyond 18 months after HCT but not during the first 18 months. In patients with GVHD, resolution of GVHD followed by withdrawal of IST was not associated with a subsequent increase in risk of relapse. In patients without GVHD, withdrawal of IST was associated with a reduced risk of relapse during the first 18 months, but the risk of subsequent relapse remained considerably higher than in patients with GVHD. In summary, the association of GVHD with risk of relapse changes over time after HCT. In patients without GVHD, early withdrawal of IST might help to prevent relapse during the first 18 months, but other interventions would be needed to prevent relapse at later time points.

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.

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