Allogeneic Hematopoietic Cell Transplantation (AHCT) for Primary Cutaneous T Cell Lymphoma (CTCL): a Center for International Blood and Marrow Transplant Research (CIBMTR) Review

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 364-364 ◽  
Author(s):  
Mary Jo Lechowicz ◽  
Manza Agovi ◽  
Jeanette Carreras ◽  
Hillard M. Lazarus ◽  
Ginna G. Laport ◽  
...  
Keyword(s):  
Overall Survival ◽  
Hematopoietic Cell Transplantation ◽  
Conflicts Of Interest ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Free Survival ◽  
Risk Of Progression ◽  
Total Body ◽  
Conditioning Intensity

Abstract Abstract 364 Patients (pts) with advanced stage CTCL have a poor prognosis with standard therapy whereas AHCT possibly is curative. Published experience with AHCT for CTCL is modest. We report the outcomes of a large cohort of CTCL pts receiving AHCT (N=133) reported to the CIBMTR from 2000–2009. The majority of pts 129 (97%) were diagnosed with Mycosis Fungoides or Sezary Syndrome. Only 8 (6%) received AHCT in a complete remission (CR) while 46 pts (35%) never achieved CR pre-AHCT. Most pts (83%) were transplanted beyond 12 months from diagnosis. Median (range) time from diagnosis to transplant is 29 (4-206) months. Peripheral blood was the main graft source (83% vs. 14% marrow and 3% cord blood). Donor types included: 66 HLA-identical siblings (50%), 56 unrelated donors (42%), 11 from other related donors (8%). Reduced intensity conditioning (RIC) was used in 64%. Recipients of RIC were on average older (median age 51 vs. 44 yr for myeloablative) and transplanted in later study years. Among the myeloablative regimens, cyclophosphamide with total body irradiation was the most common (38%) whereas among RIC, fludarabine in combination with busulfan, cyclophosphamide or melphalan was used in 50%. GVHD prophylaxis regimens varied. Overall mortality at 30 and 100 days was 7% and 16%, respectively. Overall survival at 6 mo and 2 yr was 75% (95% CI 67–82%) and 44% (95% CI 34–53%), respectively. Conditioning intensity was not different statistically for the overall survival of these pts (figure 1). Treatment related mortality (TRM) at 6 mo and 2 yr was 10% (95% CI 5–17%). Progression/relapse of CTCL was 44% (95% CI 34–54%) at 6 mo and 58% (95% CI 47–68%) at 2 yr. Progression free survival at 6 mo was 46% (95% CI 36–57%) and at 2 yr 32% (95% CI 23–42%). The incidence of grade II-IV acute GVHD was 36% (95% CI 22–50%) and of chronic GVHD 31% (95% CI 19–45%) in a subset of reported pts. Infection as a cause of death does not seem to be increased in CTCL transplanted pts. Conditioning intensity did not impact TRM or the risk of progression. This very large series of allogeneic HCT demonstrates feasibility in pts with advanced CTCL with a low TRM and long term progression free survival in approximately one third of pts. Progressive disease was the primary cause of treatment failure in this cohort of pts with advanced disease. Figure 1. Figure 1. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Reduced-Intensity Transplantation for Lymphomas Using Haploidentical Related Donors Versus HLA-Matched Sibling Donors: A Center for International Blood and Marrow Transplant Research Analysis

2016 ◽  
Vol 34 (26) ◽  
pp. 3141-3149 ◽  
Author(s):  
Nilanjan Ghosh ◽  
Reem Karmali ◽  
Vanderson Rocha ◽  
Kwang Woo Ahn ◽  
Alyssa DiGilio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Calcineurin Inhibitor ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Free Survival ◽  
Blood And Marrow Transplant ◽  
Gvhd Prophylaxis ◽  
Matched Sibling ◽  
Reduced Intensity

Purpose Related donor haploidentical hematopoietic cell transplantation (Haplo-HCT) using post-transplantation cyclophosphamide (PT-Cy) is increasingly used in patients lacking HLA-matched sibling donors (MSD). We compared outcomes after Haplo-HCT using PT-Cy with MSD-HCT in patients with lymphoma, using the Center for International Blood and Marrow Transplant Research registry. Materials and Methods We evaluated 987 adult patients undergoing either Haplo-HCT (n = 180) or MSD-HCT (n = 807) following reduced-intensity conditioning regimens. The haploidentical group received graft-versus-host disease (GVHD) prophylaxis with PT-Cy with or without a calcineurin inhibitor and mycophenolate. The MSD group received calcineurin inhibitor–based GVHD prophylaxis. Results Median follow-up of survivors was 3 years. The 28-day neutrophil recovery was similar in the two groups (95% v 97%; P = .31). The 28-day platelet recovery was delayed in the haploidentical group compared with the MSD group (63% v 91%; P = .001). Cumulative incidence of grade II to IV acute GVHD at day 100 was similar between the two groups (27% v 25%; P = .84). Cumulative incidence of chronic GVHD at 1 year was significantly lower after Haplo-HCT (12% v 45%; P < .001), and this benefit was confirmed on multivariate analysis (relative risk, 0.21; 95% CI, 0.14 to 0.31; P < .001). For Haplo-HCT v MSD-HCT, 3-year rates of nonrelapse mortality (15% v 13%; P = .41), relapse/progression (37% v 40%; P = .51), progression-free survival (48% v 48%; P = .96), and overall survival (61% v 62%; P = .82) were similar. Multivariate analysis showed no significant difference between Haplo-HCT and MSD-HCT in terms of nonrelapse mortality (P = .06), progression/relapse (P = .10), progression-free survival (P = .83), and overall survival (P = .34). Conclusion Haplo-HCT with PT-Cy provides survival outcomes comparable to MSD-HCT, with a significantly lower risk of chronic GVHD.

scholarly journals Improved Outcomes After Autologous Hematopoietic Cell Transplantation for Light Chain Amyloidosis: A Center for International Blood and Marrow Transplant Research Study

2015 ◽  
Vol 33 (32) ◽  
pp. 3741-3749 ◽  
Author(s):  
Anita D'Souza ◽  
Angela Dispenzieri ◽  
Baldeep Wirk ◽  
Mei-Jie Zhang ◽  
Jiaxing Huang ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Light Chain ◽  
Hematopoietic Cell Transplantation ◽  
Progression Free Survival ◽  
Marrow Transplant ◽  
Hematopoietic Cell ◽  
Post Transplantation ◽  
Free Survival ◽  
Blood And Marrow Transplant ◽  
Autologous Hematopoietic Cell Transplantation

Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.

Non-Myeloablative Allogeneic Transplantation in Patients with Relapsed or Refractory Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2759-2759
Author(s):  
Sabine Gerull ◽  
Ute Hegenbart ◽  
Martin Goerner ◽  
Axel Benner ◽  
Thomas Moehler ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Free Survival ◽  
Refractory Multiple Myeloma ◽  
Number Of Cycles

Abstract Patients with recurrent and refractory multiple myeloma have a very limited survival expectance. Allogeneic transplantation might offer an option for cure in myeloma and the recent development of non-myeloablative conditioning regimens has reduced transplant related morbidity and mortality and rendered this treatment feasible in elderly patients. The role of non-myeloablative allogeneic transplantation for multiple myeloma however, has not yet been defined. We have analyzed the results of patients with relapsed or refractory multiple myeloma treated at our institution. Between 08/1999 and 02/2004, 56 patients with relapsed (n=54) or refractory (n=2) myeloma were treated with non-myeloablative allogeneic transplantation. The median beta2microglobulin at the time of diagnosis was 2.75 mg/l, and median age at the time of transplant was 54.5 years (39.2–67.8). The median time from diagnosis to transplant was 3.6 years. Prior to allogeneic transplantation, patients received reinduction chemotherapy which included an autologous transplantation for 30 patients. The median number of previous cycles of conventional chemotherapy was 9. The conditioning regimen was 2 Gy TBI with (n=43) or without (n=3) fludarabin 3 x 30 mg/m² for 46 patients, the remaining 10 patients received a melphalan containing regimen. Acute toxicity was low with a WBC &lt; 500/μl and platelets &lt; 50/μl for a median of 0 days. Engraftment was prompt with 90 % of patients having achieved &gt; 90 % donor chimerism by day 56. Acute GvHD Grade II-IV occurred in 36 % of patients with 22 % Grade III-IV, and 61 % experienced chronic GvHD. Total transplant related mortality reached 20 %, with a day 100 TRM of 5 %. 32 patients experienced relapse or progressive disease, and 32 % of patients died due to relapse. The Kaplan-Meier estimate of overall survival and progression free survival at 18 months was 40 % and 25 %, respectively, with a median follow up of survivors of 21 months. Patients who experienced cGvHD had a significantly higher overall survival estimate (60 % vs. 20 % at 18 months, p=0.03). The number of cycles of pretreatment before allogeneic transplantation had a statistically significant negative influence on overall (p=0.02) and progression free survival (p=0.006). We conclude that non-myeloablative allogeneic transplantation is feasible in patients with relapsed multiple myeloma. The significant poor prognostic factors we identified were absence of chronic GvHD and number of cycles of pretreatment. Allogeneic transplantion should therefore be considered as an option earlier in the course of the disease.

Total Body Irradiation, Etoposide, Cyclophosphamide and Autologous Peripheral Blood Stem Cell Transplantation Followed by Randomization to Therapy with Interleukin-2 Versus Observation for Patients with Non-Hodgkin’s Lymphoma: Results of a Phase III Randomized Trial by the Southwest Oncology Group (SWOG 9438).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 326-326 ◽  
Author(s):  
John A. Thompson ◽  
Richard I. Fisher ◽  
Michael L. LeBlanc ◽  
Joseph M. Unger ◽  
Stephen J. Forman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Blood Stem Cell ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
High Grade ◽  
Survival Estimate ◽  
Free Survival ◽  
Post Transplant ◽  
Total Body

Abstract Purpose: To determine the effect of post-transplant immunotherapy with Interleukin-2 (IL-2) on the progression-free and overall survival of patients with non-Hodgkin’s lymphoma (NHL) after autologous stem cell transplantation and to assess the toxicity of post-transplant IL-2 therapy. Patients and Methods: Patients with previously treated low, intermediate, or high grade NHL (except Working Formulation Groups A and I) were treated with high-dose cyclophosphamide, etoposide, and total body irradiation (TBI) and an autologous peripheral blood stem cell transplant (PBSCT). Twenty-eight to 80 days after PBSCT, patients were randomized to treatment with IL-2 versus observation. Results: Between January 1995 and July 2004, three hundred ninety-four patients with low-grade (n=61) or intermediate-high grade NHL (n=315) were registered at one of 39 SWOG transplant centers. One hundred ninety patients did not proceed to randomization, because of patient refusal (44), grade V toxicity (30), disease progression (28), toxicity (28), or other reasons. Two hundred four patients were randomized to treatment with continuous infusion intravenous IL-2 (9 ×106 units/m2/day for four days followed five days later by 1.6 ×106 units/m2/day for 10 days) versus observation. The 4-year progression-free survival estimate for all eligible patients is 34%, and the 4-year overall survival estimate is 52%. There was no difference in progression-free survival (hazard ratio (HR) of IL-2 to observation = 0.90; p = 0.56) nor in overall survival (HR of IL-2 to observation = 0.88; p = 0.55). There were no deaths related to IL-2 treatment. Grade IV IL-2-related toxicities included hematologic (n=10), cardiovascular (4), renal/bladder (2), flu-like symptoms (1), lung (1), metabolic (1), and neurologic (1) and were reversible in all cases. Conclusions: These results confirm earlier SWOG findings that a regimen of cylophosphamide, etoposide and TBI followed by PBSCT can be administered to patients with relapsed or refractory NHL with acceptable toxicity and with encouraging progression-free and overall survival. Post-transplant therapy with IL-2 given at this dose and schedule of administration had no significant effect on post-transplant relapse, progression-free survival or overall survival.

Sequential Treatment with Rituximab and CHOP Chemotherapy in B-Cell PTLD - A New Standard in Therapy?.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 390-390 ◽  
Author(s):  
Ralf Trappe ◽  
Sylvain Choquet ◽  
Stephan Oertel ◽  
Veronique LeBlond ◽  
Tor Ekman ◽  
...  
Keyword(s):  
Overall Survival ◽  
Treatment Response ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Sequential Therapy ◽  
Marrow Transplant ◽  
Sequential Treatment ◽  
Bleeding Complications ◽  
Early Therapy ◽  
Free Survival

Abstract Purpose: This trial aimed to investigate the efficacy and safety of sequential treatment with rituximab and CHOP-21 in patients with PTLD unresponsive to reduction of immunosuppression. Methods: An ongoing prospective multicenter phase II trial was initiated in January 2003. Patients were treated sequentially with rituximab at days 1, 8, 15 and 22 followed by four cycles of CHOP-21 combined with G-CSF support starting 4 weeks after the last dose of rituximab. Results: In this 3rd interim analysis after enrolment of 75 patients 64 patients have finished the protocol. The median follow up is 19.6 months. 58 patients were diagnosed with monomorphic PTLD, 6 with polymorphic PTLD. 23 patients were kidney, 15 liver, 12 heart, 3 lung, 2 heart+lung, 3 kidney+pancreas, 1 bone marrow transplant recipients (5 others). Median age was 53 years (range 16 to 74). 59% had stage III or IV disease. 48% of tumors were EBV positive. 79% of patients had late PTLD (i.e. later than 1 year after transplantation). LDH was elevated in 67% of patients. The overall response rate of sequential therapy was 90% (CR 65%, PR 25%). Progression free survival (PFS) and disease free survival (DFS) were 71.4% and 81.2% at two years, respectively. Treatment response to rituximab (CR/PR versus SD/PD) was a significant factor predicting overall survival (OS) with OS rates of 91.3% and 56.5% at 1 year, respectively (p=0.0107). Following chemotherapy, WHO °3/4 leukopenia was observed in 38% of cycles and 16% of patients suffered from WHO °3/4 infections. There were four early therapy-associated deaths due to infections (7%). Fatal bleeding complications occurred in 3% and 5% of patients died from primary refractory disease. Conclusions: This is one of the largest prospective studies in PTLD. Sequential treatment with rituximab and CHOP-21 + G-CSF is well tolerated and highly effective. Treatment response to rituximab is predictive for overall survival. As compared to rituximab monotherapy more patients achieve a CR with sequential therapy and PFS is very much prolonged. Figure Figure

Conditioning Intensity in Allogeneic Hematopoietic Cell Transplantation (alloHCT) for Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 501-501 ◽  
Author(s):  
Ulrike Bacher ◽  
Evgeny Klyuchnikov ◽  
Jeanette Carreras ◽  
Jennifer Le-Rademacher ◽  
Ginna G. Laport ◽  
...  
Keyword(s):  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Multivariable Analysis ◽  
B Cell Lymphoma ◽  
Marrow Transplant ◽  
P Value ◽  
Unrelated Donor ◽  
Resistant Disease ◽  
Conditioning Regimens ◽  
Conditioning Intensity

Abstract Abstract 501 Non-myeloablative (NMC) and reduced intensity (RIC) conditioning approaches rely primarily on a graft-vs-lymphoma (GVL) effect and aim at reducing transplant-related mortality (TRM) associated with myeloablative conditioning (MAC). We analyzed outcomes for 396 adults (228 male) receiving alloHCT for DLBCL following MAC (n=165), RIC (n=143) or NMC (n=88) regimens between 2000 and 2009 and reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Conditioning regimens were classified using consensus criteria. Engraftment, cumulative incidences of acute and chronic graft-vs-host disease (GvHD), TRM, progression and probabilities of progression-free (PFS) and overall survival (OS) were compared between MAC and NMC/RIC. Common MAC regimens were cyclophosphamide (CY) + total body irradiation (TBI) (54%) and busulfan (BU) + CY (23%). Common RIC regimens were fludarabine (Flu) with melphalan (44%) or BU (39%) and for NMC, Flu with CY (48%) and low dose TBI (33%). Practice patterns changed with declining use of MAC regimens after 2003 (> 66% of total being MAC pre-2003 and <33% after). Donors were HLA matched siblings in 40%, 26%, 30% of MAC, RIC and NMC recipients, respectively, with 67% overall receiving unrelated donor (URD) grafts. Significant (p <0.05) baseline differences between the cohorts included: RIC and NMC recipients were older (54% and 58% >50 yrs vs 39% for MAC), more likely to have received prior autoHCT (36% and 51% vs 18%), prior radiation and more prior chemotherapy regimens (55 and 70% vs 44% with >3 regimens) than those with MAC. Recipients of RIC and NMC were less likely to have chemotherapy resistant disease (30% and 26% vs. 42% for MAC); and had a longer median interval from diagnosis to alloHCT (median 27 and 36 mo vs. 17 mo). Day 100 engraftment was more frequent in RIC and NMC recipients (99% and 97% with ANC >500/cu.mm vs. 88% for MAC, p <0.001). Acute (43–44%) and chronic GvHD incidence (37–42% at 5 years) was similar across the groups. Outcomes are summarized in Table 1. TRM at day +100 and at 5 years was significantly higher for MAC compared with RIC and NMC groups (See Table 1). Lymphoma relapse/progression at 5 years was significantly lower for MAC vs. RIC and NMC but 5 year PFS and OS at 5-years did not differ significantly. In multivariable analysis, NMC (HR 0.58, p=0.026) and later year of alloHCT (HR 0.49, p<0.001) were associated with lower TRM while Karnofsky status <90 (HR 1.51, p=0.011), chemo-resistant relapse (HR 2.79, p<0.001) and URD (HR 2.32, p<0.001) were associated with higher TRM. Higher incidence of relapse/progression was associated with NMC (HR 2.14, p=0.003), non-receipt of rituximab prior to alloHCT (HR 1.69, p=0.008) and chemo-resistant disease (HR 2.06, p=0.006). Conditioning intensity did not impact OS and PFS. In selected patients with advanced DLBCL, allogeneic HCT can induce long-term PFS irrespective of the intensity of conditioning with a lower incidence of TRM with RIC and NMC regimens. Due to increased toxicity, the use of MAC regimens has been declining in recent years. However, the incidence of RIC/NMC, risk of relapse/progression was concordantly higher in the RIC/NMC recipients so that survival did not differ significantly between conditioning regimens. Further studies are needed to clarify optimal conditioning strategies for advanced DLBCL aiming to further reduce TRM. Table 1: Parameter Intensity of Conditioning (95% CI) p-value MAC RIC NMC TRM @day +100 at 5 yrs 32% (25–39%) 24% (17–31%) 17% (10–26%) 0.029 56% (48–64%) 47% (38–56%) 36% (26–46%) 0.007 Relapse @ 5 yrs 26% (19–33%) 38% (30–46%) 40% (30–50%) 0.031 OS @ 5 yrs 18% (12–25%) 20% (13–29%) 26% (17–36%) 0.365 PFS @ 5 yrs 18% (12–24%) 15% (9–23%) 25% (16–34%) 0.309 Disclosures: Montoto: Genentech: Research Funding; Roche: Honoraria.

Haploidentical Peripheral Blood Stem Cell Transplantation with Post-Transplantation Cyclophosphamide in Primary Refractory Acute Myeloid Leukemia

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4411-4411
Author(s):  
Sarita Rani Jaiswal ◽  
Sumita Chatterjee ◽  
Aditi Chakrabarti ◽  
Sneh Bhargava ◽  
Ray Kunal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Peripheral Blood Stem Cell ◽  
Chronic Gvhd ◽  
Progression Free Survival ◽  
Disease Status ◽  
Blood Stem Cell ◽  
Post Transplantation ◽  
Free Survival

Abstract In a pilot study, 75 patients with Primary Refractory (PRef) AML without matched family donors were offered post-transplantation cyclophosphamide (PTCY) based haploidentical peripheral blood stem cell (PBSC) transplantation. Twenty-seven patients (36%) opted for haploidentical transplantation with or without further chemotherapy. There was no difference in the patient or disease characteristics amongst patients undergoing transplantation or not. The conditioning regimen comprised of FluCyMel (n=5), FluBuMel (n=17) and FluTreoTBI (n=5). MMF was tapered between days 14 and 21 posttransplant in the absence of GVHD and cyclosporine A was tapered between days 60 and 90. The progression free survival at a median follow-up of 25 months was 36.6% and 0% in the transplant and the non-transplant group (p=0.0001). Prompt engraftment was noted at a median of 14 days irrespective of disease status or conditioning regimens. Cumulative incidences of acute graft-versus-host disease (GVHD) and chronic GVHD were 26.6% and 8% respectively. The overall incidence of infections remained low, with CMV reactivation and invasive aspergillosis occurring in 9 and 2 patients respectively. CMV disease was diagnosed in 2 patients. Non-relapse mortality at 1 year was 16.7%. The incidence of disease progression was 54%. Factors positively impacting progression free survival were < 15% marrow blasts at transplant and a Natural Killer Cell Ligand Mismatch (NKLMM) donor. NKLMM, Haplotype or B scores had no impact on CMV infection or GVHD. However, Bx Haplotype was associated with lower NRM (5%, 95%CI-1-9) compared to 48.6% (95%CI 28.2-69.0) in AA Haplotype (p=0.01). Disease status did not impact the overall survival (p=0.11) in the HSCT cohort. In fact, NKLMM donors with B haplotype had the greatest impact on overall survival in both the HSCT cohort (71.4%, 95%CI 54.3-88.5%) compared to 20% (95%CI 8.8-31.2, p=0.01) in those without the same. Our data suggests PTCY based Haploidentical PBSC transplantation is feasible in patients with PRef AML and donor NKLMM might improve progression free survival, provided the conditioning protocol and the post-grafting therapy offer the optimum platform for alloreactivity of NK cells. Disclosures No relevant conflicts of interest to declare.

scholarly journals Outcomes after allogeneic hematopoietic cell transplantation with nonmyeloablative or myeloablative conditioning regimens for treatment of lymphoma and chronic lymphocytic leukemia

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 446-452 ◽  
Author(s):  
Mohamed L. Sorror ◽  
Barry E. Storer ◽  
David G. Maloney ◽  
Brenda M. Sandmaier ◽  
Paul J. Martin ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Previous Treatment ◽  
Progression Free Survival ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Cell ◽  
Free Survival ◽  
P 75 ◽  
Conditioning Intensity

Allogeneic conventional hematopoietic cell transplantation (HCT) can be curative treatment for lymphoid malignancies, but it has been characterized by high nonrelapse mortality (NRM). Here, we compared outcomes among patients with lymphoma or chronic lymphocytic leukemia given either nonmyeloablative (n = 152) or myeloablative (n = 68) conditioning. Outcomes were stratified by the HCT-specific comorbidity index. Patients in the nonmyeloablative group were older, had more previous treatment and more comorbidities, more frequently had unrelated donors, and more often had malignancy in remission compared with patients in the myeloablative group. Patients with indolent versus aggressive malignancies were equally distributed among both cohorts. After HCT, patients without comorbidities both in the nonmyeloablative and myeloablative cohorts had comparable NRM (P = .74), overall survival (P = .75), and progression-free survival (P = .40). No significant differences were observed (P = .91, P = .89, and P = .40, respectively) after adjustment for pretransplantation variables. Patients with comorbidities experienced lower NRM (P = .009) and better survival (P = .04) after nonmyeloablative conditioning. These differences became more significant (P < .001 and .007, respectively) after adjustment for other variables. Further, nonmyeloablative patients with comorbidities had favorable adjusted progression-free survival (P = .01). Patients without comorbidities could be enrolled in prospective randomized studies comparing different conditioning intensities. Younger patients with comorbidities might benefit from reduced conditioning intensity.

Factors associated with outcome after unrelated marrow transplantation for treatment of acute lymphoblastic leukemia in children

Blood ◽  
2002 ◽  
Vol 99 (6) ◽  
pp. 2002-2008 ◽  
Author(s):  
Ann E. Woolfrey ◽  
Claudio Anasetti ◽  
Barry Storer ◽  
Kristine Doney ◽  
Laurie A. Milner ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Chronic Gvhd ◽  
Marrow Transplant ◽  
Unrelated Donor ◽  
Free Survival ◽  
Gvhd Prophylaxis ◽  
Conditioning Treatment ◽  
Unrelated Donors ◽  
Total Body

Abstract Acute lymphoblastic leukemia (ALL) is the most common indication for transplantation of marrow from unrelated donors in children. We analyzed results of this procedure in children with ALL treated according to a standard protocol to determine risk factors for outcome. From January 1987 to 1999, 88 consecutively seen patients with ALL who were younger than 18 years received a marrow transplant from an HLA-matched (n = 56) or partly matched (n = 32) unrelated donor during first complete remission (CR1; n = 10), second remission (CR2; n = 34), third remission (CR3; n = 10), or relapse (n = 34). Patients received cyclophosphamide and fractionated total-body irradiation as conditioning treatment and were given methotrexate and cyclosporine for graft-versus-host disease (GVHD) prophylaxis. Three-year rates of leukemia-free survival (LFS) according to phase of disease were 70% for CR1, 46% for CR2, 20% for CR3, and 9% for relapse (P &lt; .0001). Three-year cumulative relapse rates were 10%, 33%, 20%, and 50%, respectively, and 3-year cumulative rates of death not due to relapse were 20%, 22%, 60%, and 41%, respectively, for patients with CR1, CR2, CR3, and relapse. Grades III to IV acute GVHD occurred in 43% of patients given HLA-matched transplants and in 59% given partly matched transplants (P = .10); clinical extensive chronic GVHD occurred in 32% and 38%, respectively (P = .23). LFS rates were lower in patients with advanced disease (P &lt; .0001), age 10 years or older (P = .002), or short duration of CR1 (P = .007). Thus, in addition to phase of disease, age and duration of CR1 were predictors of outcome after unrelated-donor transplantation for treatment of ALL in children. Outcome was particularly favorable in younger patients with early phases of the disease.

scholarly journals Outcomes for Allogeneic Hematopoietic Cell Transplantation for AML and High-Grade MDS in Older Adults in the Era of T-Replete Haploidentical Donor Grafts. a Single Center Multivariate Analysis

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4665-4665
Author(s):  
Zain Bashey ◽  
Scott R. Solomon ◽  
Lawrence E. Morris ◽  
H. Kent Holland ◽  
Xu Zhang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Older Patients ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Patient Characteristics ◽  
High Grade ◽  
Free Survival ◽  
Disease Free

Abstract Introduction: Outcomes for non-transplant therapy in older adults (age> 60 years) with AML or high-grade MDS have historically been poor. Allogeneic hematopoietic cell transplantation (allo-HCT) may improve these outcomes. However, many older patients will lack suitably HLA-matched sibling donors (MRD). Furthermore, many patients from ethnic minorities will lack an optimally matched unrelated donors (MUD). Additionally, the greater incidence and severity of chronic GVHD typically seen following MUD transplants may be particularly difficult to tolerate in older patients. T-replete haploidentical donor transplants (HAPLO) using post-transplant cyclophosphamide to mitigate alloreactivity may provide a suitable donor option for some older patients. However, no detailed comparison of outcomes after HAPLO to MRD and MUD donors in elderly patients with AML and high-grade MDS have been reported in the modern era.. Methods: We analyzed outcomes of patients aged > 60 years with AML or high-grade MDS who received an allo-HCT at our center between 2005 and 2015. Ex-vivo T-cell depleted transplants and cord blood transplants were excluded. Supportive care measures were identical between the three donor groups. Patient characteristics and outcome parameters were extracted from our institutional database where they had been prospectively entered. Kaplan-Meier estimates of overall survival (OS) and disease-free survival (DFS) were calculated and the cumulative incidence method with competing risks was used to calculate rates of non-relapse mortality (NRM) and relapse. Cumulative incidences of acute and chronic GVHD were estimated with death being treated as the competing risk. Cox proportional hazards models, stratified on the three transplant donor groups, were developed using OS, DFS, NRM and relapse as endpoints and other parameters as covariates. GVHD was prospectively documented by a single dedicated nurse using established criteria including NIH consensus criteria for chronic GVHD and rates calculated using the cumulative incidence method. Results: Patient characteristics (n=127, 33 HAPLO, 37 MRD, 57 MUD) were as follows: median age 64 (60-77); male 57%; regimen- myeloablative (24%) non-myeloablative (76%); graft- PBSC (80%) BM (20%); Diagnoses- AML 59%, MDS 41%; DRI- low (2%), intermediate (58%), high (39%), very high (1%); Sorror HCT-comorbidity index 0-2 (46%), >3 (54%); Median HLA mismatches were 5/10 (range 2/10 to 5/10) for HAPLO patients. Estimated rates of OS, DFS, NRM and relapse for the entire group at 2 years were 60%, 49%, 18%, and 33%. When compared to MRD and MUD, HAPLO patients had similar characteristics but were less likely to have myeloablative conditioning (6% vs. 32% and 30% respectively for MRD and MUD, p=0.016) and were more likely to have a BM graft (52% vs. 0% and 21%, p<0.001). Median follow-up of surviving patients following MRD, MUDT and HAPLO transplants were 34m, 26m and 17m. For MRD, MUD, and HAPLO transplants respectively, estimated outcomes are as follows: TRM at 1year: 14%, 14% and 9% and 2yrs 17%, 23%, 9%, Relapse at 1year - 25%, 34%, 22% and 2 yrs -32%, 34%, 33%; OS at 1 yr 72%, 72%, 77% and 2 yrs - 62%, 55% , 67%. DFS at 1 yr - 61%, 52%, 69% and 2 yrs - 51%, 43%, 58% (Fig 1.) (p=NS for all endpoints on pointwise and global comparison). The cumulative incidences of acute GVHD at 180 days were: grade 2-4 - 27%, 37% and 39%; grade 3-4 - 8%, 18% and 15% (p=NS for all) and chronic GVHD at 2 yrs were: moderate to severe - 38%, 35%, 15% (p=0.028 MUD vs HAPLO, p=0.026 MRD vs HAPLO); severe - 12%, 11%, 0% (p=0.030 MUD vs HAPLO, p=0.009 MRD vs HAPLO). On multivariable Cox analysis, donor type was not a significant predictor of OS, DFS, NRM or relapse (Table 1). Conclusions: The results show that in the current era, using predominantly non-myeloablative conditioning regimens, 2 year OS and DFS rates of 60% and 49% with a NRM <20% can be achieved in patients aged >60 years who undergo allo-HCT for AML and high-grade MDS. Outcomes of patients transplanted from HAPLO donors are comparable to those from matched donors although the rate of clinically significant chronic GVHD appears significantly less following HAPLO transplants, which may translate to an improved quality of life. Figure 1 Figure 1. Figure 2 Figure 2. Table 1 Multivariate Analysis on Overall Survival, Disease Free Survival, Transplant Related Mortality and Relapse Table 1. Multivariate Analysis on Overall Survival, Disease Free Survival, Transplant Related Mortality and Relapse Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document