Allogeneic Stem Cell Transplantation With Reduced Intensity Conditioning Regimen In Patients With Relapsed Hodgkin´s Lymphoma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5511-5511
Author(s):  
Maria Marta Rivas ◽  
Mariano Berro ◽  
Sebastian Yantorno ◽  
Maria Virginia Prates ◽  
Jorge H Milone ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract Introduction Hodgkin´s Lymphoma (HL) is a highly curable disease. However, there are still patients with primary refractory disease or who relapse after first-line treatment, or even after high-dose chemotherapy with hematopoietic cell rescue. Allogeneic stem cell transplant (ASCT) is therapeutic for this patients. Objective To analyze the experience with relapsed HL patients that received ASCT with reduced intensity conditioning (RIC)regimen in 8 Argentine Medical Centers. Design and Population We performed a retrospective multicenter analysis from data obtained from medical records. Fifty-four patients with relapsed HL who received ASCT had a median age of 26years. The relationship between male / female was 1/1. Only 3 patients (5.5%) at the time of transplant had a performance status> 1 according to ECOG. Ninety-six percent of the patients had received previously autologous transplant. Most patients 43 (80%) received an identical sibling donor transplant. All patients receiving unrelated donor transplants had in vivo lymphocyte depletion as prophylaxis of graft versus host disease. Forty-three patients (79.6%) received as a conditioning regimen Fludarabine + Melphalan. The disease status at transplant was: complete remission (CR) 33%, partial remission (PR) 54%, stable disease / progressed (SD / PD) 13%. Results With a median follow up of 2.7 years, actuarial overall survival (OS) at 1 and 5 years was 65% and 20% respectively and disease free survival (DFS) at 1 and 5 years was 35 % and 18% respectively. The incidence of acute GVHD grade II-IV was 31%. Patients in CR at the time of transplant showed significant differences compared with those who were not in CR in DFS (1-5 years 52-27% vs 19-14%, p=0.01), OS (1-5 years 76-38% vs 59-13%, p=0.02) and non relapsed mortality (NRM) (1-5 years 6-12% vs 34-39%, p=0.04). Age, PS, the use Fludarabine + Melphalan as conditioning regimen, unrelated donor, aGVHD, were not variables that modified the overall survival and disease-free survival. Conclusion The ASCT with RIC regimen is a feasible therapeutic option in patients with HL, especially in patients who can achieve CR. The low rate of DFS is still an issue in this setting, may be new drugs may help in optimizing pretransplant response status to improve patients’ outcome. Disclosures: No relevant conflicts of interest to declare.

Allogeneic and Matched Unrelated Donor Hematopoietic Stem Cell Transplantation (HSCT) for Hematologic Malignancies Using a Modified Reduced Intensity Conditioning Regimen.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5324-5324
Author(s):  
Marion Raflores ◽  
James Rossetti ◽  
John Lister ◽  
Richard Shadduck ◽  
John Lech ◽  
...  
Keyword(s):  
Stem Cell ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Reduced Intensity Conditioning Regimen ◽  
Disease Free ◽  
Related Mortality

Abstract INTRODUCTION:Use of a reduced intensity conditioning regimen (RICR) in hematopoietic stem cell transplant may result in lower treatment related mortality (TRM), less acute graft versus host disease (aGVHD) and better survivability, utilizing the graft versus tumor effect from HSCT. METHODS: Our institution’s original RICR protocol conditioning regimen (Trial A) consists of fludarabine 30 mg/m2 (Day-5 to D-2), melphalan 140–180 mg/m2 (Day -3) and ethyol 910 mg/m2 (Day-3) in addition to mycophenolate mofetil 1 g q12H and tacrolimus(serum level 5–15 ng/ml) beginning Day -3 as immunosuppressive therapy. Transplantation was done using peripheral blood stem cells from the best HLA-antigen match sibling (allo) or matched unrelated donor (MUD). We retrospectively compared transplant data from this original protocol to a modified RICR protocol (Trial B) using a lower dose of melphalan 100mg/m2 and addition of thymoglobulin 2mg/kg/d (D-2 to D0). RESULTS: 46 patients were transplanted in Trial A with median age of 46 years. 25 patients had allogeneic and 21 had MUD transplant. 30 patients were transplanted in Trial B with median age of 44 years. 22 patients had an allogeneic and 8 had a MUD transplant. All patients were heavily pretreated with 13 patients in Trial A and 9 patients in Trial B have undergone at least one previous stem cell transplant. At D30, all patients in Trial B were alive while 11% of patients in Trial A died of treatment related cause. At D100, 51% of patients in Trial A and 70% of patients in Trial B were alive. D100 TRM was 40% in Trial A and 20% in Trial B. Table 1. Treatment Outcome OS(%) TRM (%) RM (%) Trial A Trial B Trial A Trial B Trial A Trial B OS:overall survival TRM:treatment related mortality RM: relapse mortality 30 Days MUD 81 100 19 0 0 0 Allo 96 100 4 0 0 0 Total 89 100 11 0 0 0 100 days MUD 40 63 60 38 0 0 Allo 60 73 24 14 16 14 Total 51 70 40 20 9 10 1 year overall survival was 30% in trial A and 20% in Trial B. 1 year disease free survival (DFS) was 18% in trial A and 13% in Trial B. Table 2. 1 year treatment outcome* Overall Survival(%) Disease Free Survival (DFS) % Trial A Trial B Trial A Trial B *for Trial B, 5 living patients have not yet reached 1 year follow-up MUD 21 13 14 0 Allo 37 23 21 18 Total 30 20 18 13 Incidence of aGVHD≥2 in patients not receiving DLI and alive for more than 30 days post transplant was 56% in Trial A (MUD 67%, Allo50%) and 25% in Trial B (MUD63%, Allo 6%). At D100, aGVHD was the most common cause of death in Trial A while overwhelming sepsis was leading cause of death in Trial B. WBC engraftment with ANC>500 was achieved in 98% of patients in Trial A and 93% of patients in Trial B. Average day of engraftment was 13 days in Trial A and 15 days in Trial B. Platelet engraftment with platelet count at least 20,000 was achieved in 80% of patients in both protocols with average day of engraftment at 18 days in Trial A and 21 days in Trial B. 95% of patients in Trial A had achieved at least 80% donor marrow cells at D100 while only 81% achieved this level of chimerism in Trial B. CONCLUSION: The modified RICR protocol for HSCT is a tolerable regimen which results in a lower incidence of D100 TRM and aGVHD but overall and disease free survival are not improved. Marrow engraftment is achieved although slightly delayed compared to the original protocol.

Allogeneic Hematopoietic Stem Cell Transplantation in Elderly Patients - A Single Center Study.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3030-3030
Author(s):  
Michael Stadler ◽  
Bernd Hertenstein ◽  
Juergen Krauter ◽  
Stefanie Buchholz ◽  
Elke Dammann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Elderly Patients ◽  
Cell Transplantation ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Myelogenous Leukemia ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract Allogeneic hematopoietic cell transplantation (alloHSCT) has curative potential in many hematologic malignancies; however, substantial treatment related toxicity has restricted its use to younger patients (mostly under 55 years of age). With the development of conditioning regimens of reduced intensity, alloHSCT is being applied more widely in elderly patients, too. Here we report the results of all consecutive alloHSCT recipients above the age of 55 years transplanted at our institution between October 1996 and April 2006. Among 89 elderly patients transplanted, 50 patients were in the age group over 55 to 60 years, 31 patients in the cohort over 60 to 65 years, and 8 patients were older than 65 years. 36 patients were female and 53 male. Diagnoses included acute lymphoblastic leukemia (ALL, 10 patients), acute myelogenous leukemia (AML, 32), myelodysplastic syndromes (MDS) or secondary AML (30), chronic myelogenous leukemia (CML, 5), agnogenic myeloid metaplasia (AMM, 3), lymphoma (5), and multiple myeloma (4 patients). Advanced disease was present in 63 patients (71%) at the time of transplant. 85 patients (96%) had a WHO performance score of 0 or 1. Conditioning regimen was myeloablative in 20 patients (22%) and of reduced intensity in 69 patients (78%); in 46 patients (52%) irradiation was part of the conditioning regimen. Stem cell source was peripheral blood in 83 patients (93%) and bone marrow in 6 (7%). 32 patients (36%) received a graft from a related donor and 57 (64%) from an unrelated donor. After a median follow-up of 9 months (range: 1 to 104), 24 patients have since relapsed (27%). Treament related mortality was 27% (24 of 89 patients). 34 patients developed acute graft-versus-host disease (GvHD, 38%) and chronic GvHD was diagnosed in 25 of 71 patients at risk (35%). As of August 1st, 2006, 47 of 89 patients were alive and 41 of 89 in complete remission. Probabilities of overall and disease-free survival at three years were 45 and 32%, respectively. Interestingly, overall and disease-free survival were similar among the three age cohorts. In conclusion, according to our experience, alloHSCT is feasible in elderly patients of appropriate performance status, with acceptable relapse rates and toxicity. Figure Probability of overall survival in elderly patients after alloHSTC Figure Probability of overall survival in elderly patients after alloHSTC

Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning (RIC) Regimen Has the Capacity To Produce Durable Remissions and Long Term Disease-Free Survival in Patients with High Risk Acute Myeloid Leukemia (AML).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1141-1141
Author(s):  
S. Tauro ◽  
S. Mackinnon ◽  
K. Peggs ◽  
G. Begum ◽  
P. Mahendra ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Disease Free Survival ◽  
Allogeneic Transplantation ◽  
Disease Relapse ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Disease Free ◽  
Reduced Intensity

Abstract The toxicity of allogeneic stem cell transplantation (SCT) can be substantially reduced by the use of a reduced intensity conditioning (RIC) regimen and this has increased the proportion of patients with myeloid malignancies eligible for allogeneic transplantation. However, the capacity of RIC allografts to produce durable remissions in patients with AML and MDS has not yet been defined and consequently their role in the management of these diseases remains conjectural. Seventy-six patients with high risk AML or MDS were allografted using a fludarabine/melphalan RIC regimen incorporating alemtuzumab. The median age of the cohort was 52 years (range 18–71 years). There were 46 males and 30 females; 41 patients received an allograft from an unrelated donor and 35 from a matched sibling donor. The 100 day transplant related mortality was 9% and no patient developed greater than Grade 2 graft-versus-host disease (GVHD). With a median follow-up of 36 months (range 13–70 months) 27 patients were alive and in remission with a 3y actuarial overall survival (OS) and disease-free survival (DFS) rate of 41% and 37% respectively. The 3y OS and DFS of patients with AML in complete remission (CR) at the time of transplantation was 48% and 42% respectively. In a multivariate setting, Cox regression analysis demonstrated prognostic significance of disease stage at the time of transplant with improved DFS in patients with AML in CR at the time of transplantation (HR=2.03, 95% CI=1.02–4.07). Disease relapse was the commonest cause of treatment failure occurring at a median time of 6 months post-transplant. Fourteen out of 27 (52%) patients relapsed within 6 months and 23/27 (85%) within twelve months defining a relatively narrow window for therapeutic intervention to prevent disease recurrence. The extended follow-up in this series identifies a high risk of early disease relapse but provides evidence that RIC allografts are capable of producing sustained disease free survival in a significant number of patients with AML who would be ineligible for allogeneic transplantation using a myeloablative conditioning regimen.

Gemtuzumab Ozogamicin as Part of Reduced-Intensity Conditioning in Patients with Relapsed or Refractory Acute Myeloid Leukemia - Results of a Phase I/II Trial.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1997-1997
Author(s):  
Martin Bornhaeuser ◽  
Thomas Illmer ◽  
Platzbecker Uwe ◽  
Ordemann Rainer ◽  
Schetelig Johannes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Free Survival ◽  
Gemtuzumab Ozogamicin ◽  
Sinusoidal Obstruction Syndrome ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Conditioning Therapy ◽  
Disease Free ◽  
Reduced Intensity

Abstract Gemtuzumab ozogamicin (GO) has been associated with an increased risk of liver sinusoidal obstruction syndrome (SOS) when applied within three months before or after allogeneic stem cell transplantation. In addition, excess of liver toxicity has been observed when GO was used directly before conventional intensive preparative regimens. We hypothesized that GO might be safe and effective as part of a fludarabine-based reduced-intensity conditioning regimen. 30 patients relapsing after conventional induction chemotherapy (n=17) or after previous transplantation (autologous n=3; allogeneic n=10) have been included in a prospective phase I/II trial. Per protocol the preparative regimen contained 6 mg/sqm and 3 mg/sqm GO on day-21 and day-14 followed by fludarabine 120 mg/sqm, 200 or 800 cGy total-body irradiation (TBI; depending on age and pretreatment) and stem cell infusion during GO-induced aplasia. Five patients who had previously undergone TBI received melphalan 140 mg/sqm. GvHD prophylaxis was performed with tacrolimus (starting day-1) and mycophenolate mofetil (1.5g BID from day 0). Four patients with progressive disease after GO did not proceed to conditioning therapy and went off study. A reduction of marrow blast counts after GO monotherapy was achieved in 15/30 patients (50%). In 11 cases without response to GO, an additional salvage regimen containing anthracyclines and high-dose cytarabine was administered before conditioning therapy and transplantation. 26 patients received G-CSF mobilized peripheral blood progenitor cells from matched-sibling (n=6) or unrelated donors (n=20). Primary engraftment was observed in all cases. With a median follow-up of 20 months (range 6–55) only one patient experienced sinusoidal obstruction syndrome which was reversible after treatment with defibrotide. Grade II-IV acute GvHD occurred in 15 patients (54%). Nine patients are alive in complete remission. Reasons for death in the other patients were relapse/progression (n=10) and GvHD/Infection (n=7). The probability of overall and disease-free survival at two years for patients having received a transplant is 38% and 32%, respectively. Blast reduction after GO was associated with a superior disease-free survival (48%, p=0.1). These data suggest that GO can be integrated into reduced-intensity conditioning therapy before allogeneic stem cell transplantation in patients with relapsed AML. Refractory patients with no response to GO monotherapy have a low chance of cure and should probably receive other combination therapies.

Incorporating Target Immunotherapy into Standard Conditioning Regimen Prior to Autologous Stem Cell Transplantaion (ASCT) Improves the Transplant Outcome for Pateints with Relapsed/Refractroy B Cell Non-Hodgkin Lymphoma (B-NHL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1911-1911
Author(s):  
Mohamed I. Farhat ◽  
Reem Karmali ◽  
Stephanie A. Gregory ◽  
Parameswaran Venugopal ◽  
Mohamad Kassar ◽  
...  
Keyword(s):  
Stem Cell ◽  
Disease Progression ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Cell Transplant ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract Background: Refractory or relapse B-NHL has a poor prognosis with conventional chemotherapy. Autologous stem cell transplant (ASCT) preceded by high dose chemotherapy has been the preferred therapeutic choice for such patients. The majority of the treatment failures occur within one to two years post transplant with disease progression after transplant accounted for most of the failures. The incorporation of targeted immunotherapy (rituximab) into the upfront and relapse setting is becoming of the standard of care for patients with B-NHL. The objective of this study is to evaluate the impact of rituximab (R) on disease free survival (DFS) when added to a standard conditioning regimen -- BEAM (carmustine, cytarabine, etoposide, and melphalan) prior to ASCT. Methods: A single institution retrospective analysis of 53 patients (pts), whom were heavily pre-treated, underwent ASCT between 08/98 & 07/06. All pts received rituximab in combination with high dose cytoxan for stem cell mobilization. 37 pts received R-BEAM and 16 received BEAM prior to ASCT. Actuarial rate for DFS was estimated from the day of SCT using the Kaplan-Meier method. Results: The group was predominantly men, 73% and 78%, with a median age of 57 years for both the R-BEAM and BEAM group. With a median follow up of 15.7 months, 13/37 (32%) and 11/16 (64%) pts who received R-BEAM and BEAM respectively developed disease progression after ASCT. The 2-yr actuarial disease-free survivals (figure1) were 60% and 21% for the R-BEAM and BEAM arm respectively (p=0.006). Conclusion: In this study, the outcome of pts who received R-BEAM compares favorably to those who receive BEAM alone with significant improvement in disease-free survival. Thus, incorporating target immunotherapy into standard conditioning regimen may have altered the natural history of the disease for pts undergoing ASCT for relapsed/refractory B-NHL. Disease Free survival Disease Free survival

Reduced Intensity Allogeneic Tranplants Are Well Tolerated In Patients Over the Age of 60: Identification of Factors Predicting Overall Survival

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2361-2361
Author(s):  
Emmanouil Nikolousis ◽  
Sandeep Nagra ◽  
Janice Ward ◽  
Fiona L Dignan ◽  
Bronwen E. Shaw ◽  
...  
Keyword(s):  
Overall Survival ◽  
Older Patients ◽  
Disease Free Survival ◽  
Unrelated Donor ◽  
Free Survival ◽  
Post Transplant ◽  
Comorbidity Index ◽  
Bed Days ◽  
Disease Free ◽  
Reduced Intensity

Abstract Abstract 2361 Introduction: Reduced intensity allogeneic transplants represent a potentially curative therapy in older patients with haematological malignancies. However the upper age limit for transplantation using a sibling or unrelated donor is unclear and few studies have addressed this important issue. In the UK in vivo T cell depletion utilising alemtuzumab is commonly used as a strategy to reduce the risk of acute and chronic graft-versus-host disease (GVHD) but this manoeuvre impairs immune reconstitution and may pose a particular problem in older patients. Aim: We analysed the outcome of patients over the age of 60 after an alemtuzumab based reduced intensity allograft from five UK Transplant Centres with the aim of identifying factors determining long term outcome and also factors affecting the duration of inpatient admission during the first 100 days post transplant. A modified Charlson's comorbidity index score (Sorror modified HCT comorbidity index) was applied to analyse the transplant outcomes of these patients according to the presence of transplant co-morbidities. Patients and Methods: We have studied the outcome of 161 patients (89 male, 72 female) after an alemtuzumab conditioned reduced allograft allograft for a haematological malignancy. The median age of the patients was 62 years(range 60–72). 115 patients had a transplant for myeloid malignancies (87 acute myeloid leukaemia, 21 myelodysplastic syndrome, 2 chronic myeloid leukaemia, 5 myelofibrosis) and 46 for lymphoid malignancies (18 Non_Hodgkin's lymphoma, 14 chronic lymphocytic leukaemia, 4 T-prolymphocytic leukaemia, 7 multiple myeloma and 3 acute lymphoblastic leukaemia). 93 patients received an unrelated donor transplant and 68 had a sibling transplant. The great majority of patients were transplanted using a Fludarabine/Melphalan conditioning regimen(n=118) whilst 13 received a combination of fludarabine and busulphan, 21 BEAM (BCNU, cytarabine, etoposide, melphalan) and 9 a combination of BEAM and fludarabine. The median follow up was 19.1 months (range 2–94 months). Results: The one year overall survival for the whole group was 52% and the predicted two year OS 46%. The transplant related mortality (TRM) was 19% in the first 100 days post transplant and 23% in the first year post transplant. 40 patients (25%) relapsed. 25 patients (21%) developed Grade III-IV acute GvHD and 16 (10%) patients developed chronic extensive GvHD. There was a weakly negative correlation between Age and Bed Days(p:0.05843) but the correlation between high comorbidity index (3 or greater than 3) and increased bed days is significant(P:0.0013). Transplant outcomes were affected by Sorror modified comorbidity index for HCT.A score of 3 and above was significantly associated with decreased overall survival (P:0.001) and interestingly with decreased disease free survival (P:0.02). CMV status and stem cell dose did not have any impact on overall survival and disease free survival and CR1 at transplantation was showed a trend towards increased overall survival(P:0.05). Conclusions: Reduced intensity alemtuzumab based stem cell transplant can be delivered safely in patients above the age of 60. It appears that a Sorror comorbidity score of 3 and above has a negative impact on overall survival and disease free survival of these patients and significantly increases inpatient days.These observations require confirmation in a larger cohort of patients but suggest that the selection of patients above the age of 60 for a reduced intensity transplants will be facilitated by incorporation of the Sorror HCI comorbidity index into a transplant algorithm. Disclosures: No relevant conflicts of interest to declare.

A Comparison of Two Different Reduced Intensity Conditioning (RIC) Allograft Strategies In Patients with Multiple Myeloma, An EBMT Analysis

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3512-3512
Author(s):  
Firoozeh Sahebi ◽  
Laurent Garderet ◽  
Simona Iacobelli ◽  
Anja van Biezen ◽  
Gösta Gahrton ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplant ◽  
Autologous Stem Cell Transplant ◽  
Cell Transplant ◽  
Calendar Period ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Reduced Intensity

Abstract Abstract 3512 Recent studies in multiple myeloma patients using reduced intensity conditioning (RIC) allograft following autologous stem cell transplant in a planned tandem fashion (auto-allo) have reported low transplant related mortality (TRM) in a range of 10–15% and long term disease control in approximately one third of the patients. Similar results are reported with reduced intensity allogeneic stem cell transplant either as upfront or salvage treatment for patients who have failed prior autologous stem cell transplant. It is not clear if RIC allograft without preceding autologous stem cell transplant can produce the same outcome. The objectives of this retrospective study are to evaluate and compare the results of planned tandem autologous-RIC allograft (auto-allo) and early RIC allograft as first transplant in order to address whether or not cytoreductive autologous stem cell transplant (ASCT) is needed in patients who are candidates for RIC allograft and patients can be spared from morbidities of autologous stem cell collection and transplant. Study: We performed a retrospective analysis of the EBMT database. Five hundred and four multiple myeloma patients were identified as auto-allograft or early RIC allograft recipient between 1998 – 2007. Three hundred and fifty six patients were assigned to planned tandem auto-allograft and 148 patients received early RIC allograft as their first transplant. All patients underwent transplant within 1 year from diagnosis. Two hundred and fifty-three of 356 patients in the auto-allo group received their planned allograft, 88 patients did not undergo the planned allograft and 15 patients had a second autologous stem cell transplant. There were no significant differences in disease stage, disease subtype, sex, use of T-cell depleted allograft and donor type (sibling vs. unrelated donor) between the 2 groups. However patients in the early RIC group were younger (median age 51 vs. 53 years old P=0.03), received transplant in earlier calendar period (51% between 1998–2002 vs. 33% P <0.001), had longer interval from diagnosis to transplant (9 vs. 6 mo. P=0.0001) and were more in CR at the time of transplant (17% vs. 9% P=0.008). The B2 microglobulin and cytogenetic data were missing in the majority of patients and therefore not included in this analysis. Results: Results are reported on an intention to treat (ITT) analysis. With a median follow up of 52 mo. (48-55) in the auto -allo and 48 mo. (39-55) in the early RIC group best response occurred more frequently in the auto-allo group than early RIC with complete response rate of 62% vs. 47% respectively. Progression-free survival at 3 and 5 years were significantly better in the auto-allo group (43% and 31% respectively) as compared to the early RIC group (30% and 17% respectively, P<0.001). Overall survival was also significantly improved in favor of the auto-allo group with 3 and 5 year OS of 68% and 60% as compared to 52% and 37% in the early RIC group (P<0.001). Non Relapse Mortality (NRM) rates at one year were 9% and 18% in the auto-allo and early RIC group respectively (p <0.001). There were no differences in the incidence of acute GVHD (41% vs. 43% P=0.13) and chronic GVHD (60% vs. 56% P=0.19) between the auto-allo and RIC groups respectively. Given the differences in the calendar year we compared the PFS and overall survival between the two groups within the same calendar period (1998-2002 and 2003–2007). Log rank test confirmed significantly better outcome in favor of the auto-allo group in each calendar period suggesting that the observed differences between the 2 groups were independent of the calendar period. (P<0.001). Conclusion: This large retrospective study on an ITT analysis suggest cytoreductive autologous stem cell transplant (ASCT) prior to RIC allograft is associated with improved disease free survival and overall survival in patients with multiple myeloma who are candidates for RIC allograft. Disclosures: Sahebi: Millennium Pharmaceuticals, Inc: Research Funding.

scholarly journals Haploidentical Allogeneic Hemopoietic Stem Cell Transplant for High Risk Myelodysplastic Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3173-3173
Author(s):  
Anna Maria Raiola ◽  
Sara Aquino ◽  
Germana Beltrami ◽  
Stefania Bregante ◽  
Fabio Cruciani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Myelodysplastic Syndrome ◽  
Chronic Gvhd ◽  
Disease Free Survival ◽  
Hemopoietic Stem Cell ◽  
Unrelated Donor ◽  
Cell Transplant ◽  
Platelet Recovery ◽  
Free Survival ◽  
Disease Free

Abstract Introduction Allogeneic hematoopoietic stem cell transplantation (HSCT) is the only today available curative treatment for Myelodysplastic Syndrome (MDS) patients. Wide approach to transplant has been hampered by HLA compatible donors availability, advanced diseases, donor and patients advanced age. In the recent years improvement of haploidentical HSCT has offered to many patients the opportunity to undergo this curative approach. The Genova transplant team included haplo HSCT for MDS in his standard operative procedure since 2011. Therefore this unselected consecutive patients cohort offers the possibility to verify feasibility of haplo HSCT in MDS patients. Patients and Methods. Form August 2011 since March 2016 thirty (30) consecutive patients were transplanted from an haploidentical donor in our center. All of them were lacking an HLA identical family donor and an 8/8 matched unrelated donor. Table 1 reports patients and disease characteristics. All donors were haploidentical family member. Conditioning regimen was myeloablative for 10 patients and reduced intensity for 20 patients as previously reports (Raiola et al Biol Blood Marrow Transplant. 2013; 1:117-22). Patients received a median of 3.1 x10e8 /kg (range 1.1 -6) un-manipulated marrow derived nucleated cells. Graft versus host disease (GvHD) prophylaxis consisted in post transplant cyclophosphamide 50 mg/kg , on day+3 and +5 , cyclosporine (from day 0) , and micophenolate (from day +1). Data are expressed and median with a range unless indicated. Disease free survival and GvHD rate are calculated with the methods of Kaplan and Meier. Results Hematologic recovery was complete in 28 (93%) patients. The median times to neutrophil (>500/μL) and platelet recovery (>20,000/μL) was 18 days (range, 14-24 days) and 25 days (range, 12 - 51 days), respectively. Two patients had autologous recovery and were successfully re-transplanted with the same protocol. The incidence of acute GVHD grade II-IV was 15%. No early death was registered. Two patients died, in complete remission of MDS, at 389 (chronic GVHD + sepsis) and 1123 (interstitial pneumonitis) days after transplant, respectively. Seven patients relapsed at median time from transplant of 188 days (range 139 - 560 days). All relapsed patients subsequently died by disease progression. The incidence of chronic GVHD was 20% (6 patients, severe in 5). At the time of this report of the 21 surviving patients (all in remission by MDS) two are under chronic GvHD treatment. With a median follow up of 20.5 months (range 4 - 54) the 3 years probability disease free survival is 69% (95%, CI 51-87). Discussion Haploidentical transplant, together with conventional donor approach, offers the majority of patients the possibility to undergo HSCT. The data here presented demonstrated feasibility of the procedure in advanced disease patients even by an haploidentical donor. In our knowledge no similar results are achievable by today available or experimental medical therapy. HSCT transplantation, even from haploidentical donor, should be offered to all MDS patients presenting with this indication. Disease relapse is the most important cause of transplant failure. Disclosures Angelucci: Novartis oncology, celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees.

Clonal Gammopathies Following Reduced Intensity Conditioning Transplantation with Fludarabine, Busulphan and Alemtuzumab for Myeloid Malignancies Predict Improved Overall Survival.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1410-1410
Author(s):  
ZiYi Lim ◽  
Antonio Pagliuca ◽  
Wendy Ingram ◽  
Dragana Milojkovic ◽  
Mojtaba Akthari ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Disease Free Survival ◽  
Autoimmune Disorders ◽  
Disease Stage ◽  
Reduced Intensity Conditioning ◽  
Free Survival ◽  
Myeloid Malignancies ◽  
Disease Free

Abstract Clonal gammopathies and autoimmune disease following standard conditioning haematopoietic stem cell transplantation (HSCT) are thought to reflect immune dysregulation post HSCT. Serial serum protein electrophoresis was performed on 124 patients with myeloid malignancies undergoing Alemtuzumab based reduced intensity conditioning (RIC) HSCT. The median age of patients was 53 years (range 22–72), with a median follow-up of 521 days (range 82–2096). The median follow-up for survivors was 720 days (range 82–2096). The majority of patients were treated for myeloid malignancies: MDS 84, AML 28, CML 10, others 2. There were 45 sibling and 79 VUD allografts. All patients received the same RIC protocol with FBC (30mg/m2 fludarabine iv day −9 to −5, 4 mg/kg busulphan oral from day −3 to −2; and 20 mg alemtuzumab iv from day −8 to −4) conditioning with cycloporine A for GvHD prophylaxis. Patients with autoimmune disorders or clonal gammopathies prior to transplant were excluded from the study. We observed the presence of clonal gammopathies in 49 patients (40%). On analysis of immunoglobulin sub-classes, the M component was identified as monoclonal in 21 (43%), biclonal in 16 (33%) and oligoclonal in 12 (24%). The predominant Ig isotype was IgG (84%), and gammopathies were present for a median time of 138.5 days (range: 27–462). The kappa:lambda ratio between samples was 1.6:1. The median level of gammopathies was 2.6 g/l (range 1.0–16.5). There was no evidence of plasma cell dyscrasia on bone marrow assessment in any of the patients. We compared the characteristics of patients with and without gammopathies. There were no significant differences in donor or recipient age, sex, disease type, stem cell source, stem cell dose. The incidence of viral infections, acute GvHD, donor lymphocyte infusion (DLI) was similar between the groups. However, patients with gammopathies were more likely to have chronic graft versus host disease (GvHD) (p=0.006). Bone marrow chimerism was available for analysis on 45 patients. At time of detection of gammopathy, 34 patients (76%) had achieved full donor chimerism, and 11 patients (24%) were mixed donor chimerism. Of the entire group of 124 patients, 11 patients (9%) developed autoimmune disorders. There was however no association between the presence of autoimmune disorders and clonal gammopathies (p=0.50). When patients with gammopathies were compared with those without, there was a significant difference in both disease free survival (54% vs 24%, p=0.012), and overall survival (69% vs 45%, p=0.007). On univariate analysis, early disease stage and presence of gammopathy were significant predictive variables for improved disease free survival and overall survival. On multivariate analysis, disease stage was the only independent variable for disease free survival (p&lt;0.01, HR 2.345, 95% CI 1.282–4.288), and both disease stage (p=0.05, HR 1.901, 95% CI 1.000–3.615) and presence of gammopathy (p=0.01, HR 0.421, 95% CI 0.217–0.815) were independent predictors of overall survival. The role of humoral responses following transplantation is still undefined, and it is possible that the gammopathies seen in our cohort are a surrogate response to a heterogenous group of stimuli. Clonal gammopathies are a frequent and benign occurrence following RIC HSCT, and its appearance may define a subgroup of patients with a favourable overall outcome.

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