Reduced Intensity Conditioning Regimen for Allografting Following Cytoreductive Autografting in Relapsed/Resistant Hodgkin’s Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5135-5135
Author(s):  
Michele Carella ◽  
Germana Beltrami ◽  
Maria T. Corsetti ◽  
Mario M. Greco ◽  
Potito Scalzulli ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Progressive Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hodgkin's Lymphoma ◽  
Mixed Chimerism ◽  
Maximal Response ◽  
High Dose ◽  
Cell Transplant

Abstract Background: We postulated that it is possibile to safely extend the benefit of allografting to relapsed or resistant Hodgkin’s Lymphoma (HL) by combining cytoreduction with high-dose therapy/autologous stem cell transplant (HDT/ASCT) and graft versus HL effect mediated through transplanted donor immune cells with nonmyeloablative allografting (RICT). Methods: Twenty-two patients, 32 years of age (range, 16–39) with heavily pretreated disease were given HDT/ASCT. At a median of 92 days after HDT/ASCT the patients received fludarabine 30 mg/m2/day x 3 days and cyclophosphamide 300 mg/m2/day x 3 days and non-T depleted donor peripheral blood stem cells from HLA-identical siblings. Postgrafting immunosuppression consisted of methotrexate and cyclosporine. Cyclosporine was withdrawn early in patients with mixed chimerism or disease progression. Donor lymphocyte infusions were given to 12 patients with stable mixed chimerism and/or progressive disease. Results: Seventeen patients (77%) achieved full chimerism and 5 patients mixed chimerism. Twelve patients (55%) achieved CR after tandem transplant. The first signs of responsiveness in CR patients began at day ≥60 and the maximal response was achieved on day ≥80. The remitters patients achieved full chimerism and developed acute/chronic GVHD before regression of the disease; moreover, 5 patients achieved CR after DLI. At last follow-up (July 31, 2004), 9 out of 12 CR patients are alive at a median of 1844 days (range, 1092 to 2045). Subsequently, 5 patients relapsed and are now alive on therapy and four patients maintain CR after a median follow-up of 1874 days (range, 1092–2045). Acute GVHD grade ≥ II occurred in 9 patients (40%); chronic GVHD developed in 5 patients (23%), four of them with extensive chronic GVHD requiring further immunosuppressive therapy. Two patients died of GVHD/infections, 1 patient died of extensive chronic GVHD and 7 patients of progressive disease. Conclusions: This tandem auto-allotransplant protocol demonstrated to be highly effective also in advanced resistant Hodgkin’s Lymphoma patients. The exploitation of graft-versus-lymphoma effect is a promising finding

Non-Myeloablative Allogeneic Transplantation for Hodgkin’s and Non-Hodgkin’s Lymphoma: Evidence for a Graft-Versus-Lymphoma Effect and Relevance of Chimerism.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3041-3041
Author(s):  
Philippe Armand ◽  
Haesook T. Kim ◽  
Ann S. LaCasce ◽  
Corey S. Cutler ◽  
Vincent T. Ho ◽  
...  
Keyword(s):  
Cumulative Incidence ◽  
Hodgkin’S Lymphoma ◽  
Acute Gvhd ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Hodgkin's Lymphoma ◽  
Future Research ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma

The role of non-myeloablative allogeneic stem cell transplantation (NST) in the treatment of patients with Hodgkin’s disease (HD) or non-Hodgkin’s lymphoma (NHL) is still undefined. We report the outcomes of 87 patients with lymphoma who underwent NST at our institution. Thirty-six patients had HD and 51 had NHL (13 indolent NHL (indNHL), 23 aggressive NHL (aggNHL), and 15 mantle cell lymphoma (MCL)). Median age was 46 (18–64). Patients had received a median of 4 prior lines of therapy; 94% of the HD patients had received a previous autograft, as had 49% of NHL patients. 28% of patients were transplanted in CR, 49% in PR, and 23% with stable or progressive disease. The conditioning regimen consisted of IV busulfan (0.8 mg/kg/d × 4) and fludarabine (30 mg/m2/d × 4). Donors were matched related (38%), matched unrelated (56%), or mismatched (6%). Most patients received GVHD prophylaxis with a calcineurin inhibitor plus sirolimus or methotrexate. All patients engrafted. The 3-year cumulative incidence of non-relapse mortality (NRM) was 23%, and of relapse was 50%. The cumulative incidence of grade 2–4 acute GVHD was 16%, and the 2-year incidence of chronic GVHD was 68%. With a median follow-up of 21 months for survivors, the projected 3-year overall survival (OS) was 59% for patients with HD, 79% for indNHL, 42% for aggNHL, and 36% for MCL. The corresponding figures for 3-year progression-free survival (PFS) were 17% for HD, 59% for indNHL, 21% for aggNHL, and 30% for MCL. Figure Figure Multivariate analysis identified elevated pre-transplantation LDH and more than 4 prior lines of therapy as adverse factors for PFS, while indolent NHL histology was a favorable factor. In time-dependent multivariable models, grade 3–4 acute GVHD was associated with increased NRM and relapse, and decreased PFS and OS. Chronic GVHD was associated with a lower risk of relapse and improved PFS, without a significant effect on OS. The protective effect of chronic GVHD on relapse applied to all histologies except for aggNHL. Forty-five percent of relapsed patients (13 pts with HD and 5 with aggNHL) received donor lymphocyte infusion (DLI). The overall response rate (ORR) was 15% (2/13) for patients with HD, with both patients remaining progression-free at last follow-up; ORR was 40% (2/5) for patients with aggNHL, but responses were transient. For all patients, median chimerism at day 20–50 was 97% (range 46–100). Low early donor chimerism was not predictive of relapse, PFS, or OS in univariate or multivariate analyses. Moreover, relapse was not associated with loss of chimerism. Finally, chimerism at the time of DLI had no apparent bearing on its outcome. Conclusions: NST results in high PFS for indolent NHL. There is evidence of a graft-versus-lymphoma effect. Chimerism is not at any point predictive of relapse or of outcome. Future research could be aimed at increasing specific anti-lymphoma immune activity to harness GVL without increasing the incidence of GVHD.

scholarly journals High Incidence of HHV-6 Infection Associated with Bendamustine, Cytarabine, Etoposide and Melphalan (BeEAM) Conditioning Regimen: Results of a Monocentric and Retrospective Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5817-5817
Author(s):  
Simon Favre ◽  
Mathieu Sauvezie ◽  
Marie Sarah Dilhuydy ◽  
Stéphane Vigouroux ◽  
Reza Tabrizi ◽  
...  
Keyword(s):  
Retrospective Study ◽  
Continuous Infusion ◽  
Hodgkin’S Lymphoma ◽  
Renal Toxicity ◽  
Conditioning Regimen ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
High Incidence ◽  
Digestive Toxicity

Abstract Background: Because of the disruption of BCNU (Carmustine) in France during several months, and based on the results reported by Visani and colleagues (Visaniet al, Blood 2011) Bendamustine has been used in combination with Etoposide, Cytarabine and Melphalan (BeEAM) in a new high dose conditioning regimen before autologous transplant in relapsed/refractory (R/R) lymphoma patients. We report our experience on the safety and efficacy of BeEAM compared to the classical BEAM regimen. Patients and methods: Ninety consecutive pts (BEAM = 60, BeEAM = 30) with R/R lymphoma were enrolled between December 2013 and September 2015 (BEAM from December 2013 to January 2015 and BeEAM from February to September 2015) in this retrospective study. Pts in complete or partial response after salvage therapy received high dose conditioning with Bendamustine (d-8 and d-7), Cytarabine (400 mg/m2 continuous infusion from d-6 to d-3), Etoposide (200 mg/m2 continuous infusion from d-6 to d-3) and Melphalan (200 mg/m2 d-2) followed by ASCT on d0. Bendamustine was given at 200 mg/m2/d for the first 4pts then 100 mg/m2/d for the 4 subsequentpts and finally at 120 mg/m2/d for the remaining pts (22 pts). Among the BEAM group, 68% had Non-Hodgkin's Lymphoma (NHL) and 32% Hodgkin's Lymphoma (HL) compared to 87% and 13% respectively in the BeEAM group (p = 0,014). HHV-6 detection was performed by PCR for symptomatic pts (fever, rash or prolonged cytopenia). Patients were housed in single bedrooms with air filtration and received the same supportive care. Results: Median age was 50 (18-66) and 56 (20-67) in the BEAM and BeEAM groups respectively and median of previous chemotherapy regimens was 2 (1-5). Fifty two out of 90 patients were male (37/60 in the BEAM group and 15/30 in the BeEAM group). Pts were in CR (46, 7% Vs 56, 7%) or PR (53, 3% Vs 43, 3%) at time of transplant. There was no difference in terms of hematologic recovery (median = 11 days (range: 7-22)), blood and platelets transfusion, mucositis toxicity. There was no statistical difference in the incidence of acute renal failure when comparing the two groups. However, there was a very striking difference when considering the highest dose of Bendamustine when compared as well to the two others doses of Bendamustine (p < 0.00001) as to the BEAM group (p=0.005). Additionally, we also observed a high incidence of symptomatic HHV-6 infections (53.3% vs 8.3%, p < 0.00001), digestive toxicity (36.6% vs 15%, p = 0.03) and a longer hospitalization duration (25 days (range: 18-59) vs 21 days (range: 18-32), p = 0.001) for patients in the BeEAM group overall. With a median follow up of 18.3 and 9.7 months for BEAM and BeEAM respectively, overall survival (93% vs 86%), transplant related mortality (0% vs 3%) and event free survival (83% vs 78%) were comparable. Conclusion: Overall, BeEAM regimen was associated with longer duration of hospitalization, higher rate of digestive toxicity and increased risk of symptomatic HHV-6 infection as compared to the BEAM regimen. In addition, higher doses of Bendamustine (200mg/m2/d for two consecutive days) were associated with unacceptable high rate of acute renal toxicity. With a still short follow-up, the absence of benefit on disease control together with higher short term toxicity does not allow to recommend the use of BeAM instead of classical BEAM. Should it be used, we suggest that pts should be carefully monitored for renal toxicity and for HHV-6 infection in case of symptoms. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Autologous Stem Cell Transplantation with Bendaeam (Bendamustine, Etoposide, Cytarabine, Melphalan) As Conditioning Regimen for Non-Hodgkin’s Lymphoma and Hodgkin’s Lymphoma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2515-2515 ◽  
Author(s):  
Sylvain Garciaz ◽  
Diane Coso ◽  
Florence Broussais ◽  
Jean-Marc Schiano ◽  
Boris Calmels ◽  
...  
Keyword(s):  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
Non Hodgkin’S Lymphoma ◽  
Non Hodgkin's Lymphoma ◽  
Mantle Cell ◽  
Grade 3

Abstract Background: High dose chemotherapy followed by autologous stem cell transplantation (ASCT) remain standard of care in patients with relapsed non Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL). This regimen is also proposed as consolidation therapy in patients with poor prognosis aggressive NHL and mantle cell lymphoma in first complete remission (CR). BEAM (BCNU, etoposide, cytarabine, melphalan) is the standard protocol chemotherapy used as conditioning regimen. A few previous studies with Bendamustine replacing BCNU have been reported with promising results. BendaEAM seems to show less toxicity and might improve results in relapsed Hodgkin/non-Hodgkin’s lymphoma (R-HL/NHL) patients. Method: From January 2014 to July 2014, patients with NHL and HL were enrolled in this study. Previous therapy consisted in Rituximab (R)-CHOP (cyclophosphamide, doxorubicine, vincristine, prednisone) for all NHL patients transplanted in first CR. Patients with relapsed NHL and HL received high-dose cytarabine based salvage regimen. No patient presented significative comorbidity. Functional pulmonary test and cardiac evaluation were performed for all patients. with the conditioning regimen consisted in Bendamustine on day -7 and -6 (200 mg/m²/d), cytarabine daily from day -5 to day -2 (200 mg/m²/d), etoposide daily from day -5 to day -2 (200 mg/m²/d) and melphalan on day -1 (140 mg/m²). Autologous stem cells were infused on day 0. Prophylactic use of colony-stimulating factors was not allowed except for patients with less than 2x106 in the apheresis product. Patients received antimicrobial prophylaxis with oral fungizone. Red cells and platelets transfusions were administered to maintain hemoglobin level >8g/dl and a platelet count (PLT) >10x109/l. Broad spectrum antibiotics were delivered when fever developed. Results: There were 25 patients: 10 patients with diffuse large-B cell lymphoma and high international prognostic score (IPI) score in first CR, 5 patients with relapsed NHL or HL, 4 patients with mantle cell lymphoma in first CR, 5 patients with relapsed follicular lymphoma, and 1 patient with peripheral T cell lymphoma. A median number of 4,1x106 (range: 1.5-8.1) CD34 cells/kg was infused. All patients fully engrafted after a median time of 19.5 days (range: 14-24). Median times to PLT>20x109/l and PLT>50x109/l were 20 days (range: 16-52) and 22 days (range: 18-52) respectively. All patients experienced grade 3-4 fever with a documented infection in 9 cases Five patients were admitted in intensive care unit for septic shock and one patient died. One patient presented a total resolutive grade 4 renal failure. Three patients (12%) developed grade 3 cardiotoxicity (atrial fibrillation). No pulmonary toxicity was observed. Median time to hospital discharge was 23 days (range: 18-77). With a median follow-up of 2 months (range: 1-6) 24 patients are alive in CR. Conclusion: BendaEAM as conditioning regimen followed by ASCT is feasible in patients with NHL and HL. Toxicity of this chemotherapy is acceptable and seems comparable to that observed with the standard BEAM regimen (data will be presented). While the follow-up remains short, results are encouraging in patients with NHL or HL, as well as in first CR or subsequent CR. Thus, the use of bendamustine in lymphoma conditioning regimen can be recommended on the basis of its high anti-lymphoma activity, but also according to the safety of the drug with a lower pulmonary toxicity. Disclosures No relevant conflicts of interest to declare.

Reduced Intensity Conditioning Regimen for Allografting Following Cytoreductive Autografting in Metastatic Breast Cancer.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5129-5129
Author(s):  
A.M. Carella ◽  
Germana Beltrami ◽  
Maria T. Corsetti ◽  
Potito Scalzulli ◽  
Michele Carella ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Conditioning Regimen ◽  
Metastatic Breast ◽  
Mixed Chimerism ◽  
Maximal Response ◽  
High Dose ◽  
Cell Transplant ◽  
Breast Cancer Patients ◽  
Graft Versus Tumor Effect

Abstract We postulated that it is possible to safely extend the benefits of allografting to metastatic breast cancer by combining cytoreduction achieved with high-dose therapy and autologous stem cell transplant (HDT/ASCT) and graft versus tumor effect mediated through transplanted donor immune cells with nonmyeloablative allografting (RICT). Seventeen patients, 41 years of age (range, 31–57), with heavily pretreated disease were given HDT/ASCT. No patient died after HDT/ASCT. Thirty-one to 92 days (median, 51 days) after HDT/ASCT the patients received fludarabine 30 mg/m2/day x 3 days and cyclophosphamide 300 mg/m2/day x 3 days and donor PBPC from HLA-identical siblings. Postgrafting immunosuppression consisted of cyclosporine and methotrexate. Donor lymphocyte infusions were given to 11 patients with stable mixed chimerism and/or progressive disease, who did not show signs of GVHD. Thirteen patients (76%) achieved sustained donor engraftment. Three patients achieved partial remission (PR) after HDT/ASCT and complete remission (CR) after RICT; another no-responsive patient achieved PR for an overall response rate of 4/17 (22%). The first signs of responsiveness in CR patients began at day +80, +90 and +110 and the maximal response was achieved on day +240, +300 and +390. The 3 remitters patients achieved full chimerism and developed GVHD before regression of the disease. Grade ≥II aGVHD occurred in 5 patients (29%) and extensive cGVHD in 5 patients (29%). No transplant-related deaths (TRD) were observed during the first 100 days. Three patients died of extensive cGVHD in the first year. At April 2004, 5/17 patients (29%) are alive 90–2160 days (median, 1320) from RICT. In conclusion, this 2-step approach is a feasible procedure in metastatic breast cancer patients; the exploitation of graft versus tumor effect is a promising finding.

scholarly journals Complete Remission of Relapsed Hodgkin’s Lymphoma following Brentuximab Vedotin and Gemcitabine Combination Therapy with Severe Hypotension as Possible Treatment-Related Adverse Event: A Case Report

2020 ◽  
Vol 13 (1) ◽  
pp. 341-346 ◽  
Author(s):  
Ibnu Purwanto ◽  
Bambang P. Utomo ◽  
Ahmad Ghozali
Keyword(s):  
Adverse Event ◽  
Complete Remission ◽  
Hodgkin’S Lymphoma ◽  
Brentuximab Vedotin ◽  
Hodgkin's Lymphoma ◽  
High Dose ◽  
High Dose Corticosteroid ◽  
Severe Hypotension ◽  
Dose Corticosteroid

A 40-year-old Asian female with heavily treated relapsed Hodgkin’s lymphoma showed complete remission (CR) after receiving 8 cycles of brentuximab vedotin (BV) in combination with gemcitabine as 4th line treatment. The patient remained in CR at the 18-month post-treatment follow-up. She developed severe hypotension (50/36 mm Hg) with upper and lower limb petechiae and edema after the addition of gemcitabine on the 6th cycle of BV. This adverse event resolved after 3 days of treatment with vasopressor and high-dose corticosteroid. The addition of dexamethasone for the subsequent 2 cycles successfully prevented this adverse event from recurring.

High-dose chemotherapy and peripheral hematopoietic stem cell transplantation in relapsed/refractory Hodgkin’s lymphoma

2018 ◽  
Vol 104 (6) ◽  
pp. 471-475 ◽  
Author(s):  
Mouhammed Kelta ◽  
Jamal Zekri ◽  
Ehab Abdelghany ◽  
Jalil Ur Rehman ◽  
Zahid Amin Khan ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hodgkin’S Lymphoma ◽  
High Dose Chemotherapy ◽  
Salvage Chemotherapy ◽  
Hodgkin's Lymphoma ◽  
Phase Iii ◽  
High Dose

Purpose: High-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) is used to treat patients with relapsed Hodgkin’s lymphoma. In this retrospective study we report our experience with patients who underwent HDCT and ASCT. Methods: All patients ≥15 years old with relapsed/refractory Hodgkin’s lymphoma who underwent HDCT and ASCT between June 2001 and December 2013 were included. Results: Fifty-four patients were identified. Median age at transplant was 22 years (range 15-49 years); 26 were men and 28 were women. Forty-eight patients (89%) underwent HDCT and ASCT after achieving a radiological response to salvage chemotherapy. The rate of radiological complete response to salvage chemotherapy was 13% and reached 50% within 3 months of ASCT in assessable patients. After a median follow-up of 25 months, 31 patients (57%) were still alive with no evidence of relapse or progression. Median event-free survival (EFS) was 24 months (95% CI 8.7-39.3) and 3-year EFS was 56%. Median overall survival (OS) was not reached and 3-year OS was 82.5%. Bulky mediastinal disease at relapse, hemoglobin level, and number of salvage regimens did not significantly impact EFS in univariate and multivariate analyses. After transplantation there was a trend towards longer EFS (30 vs. 24 months; p = 0.36) in patients with a longer time from the end of first-line treatment until relapse (≥12 vs. <12 months). The 100-day transplant-related mortality was 5.5%. Conclusions: HDCT and ASCT for relapsed/refractory Hodgkin’s lymphoma is safe. Our findings are consistent with published phase III results. Longer follow-up is warranted.

Holmium-166 (166Ho)-DOTMP Skeletal Targeted Radiotherapy (STR™) with Melphalan and Autologous Peripheral Stem Cell Transplant (PBSCT) for Multiple Myeloma (MM).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 922-922 ◽  
Author(s):  
Mark Goodman ◽  
William I. Bensinger ◽  
Sergio Giralt ◽  
Donna Salzman ◽  
Katherine L. Ruffner ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Hemorrhagic Cystitis ◽  
Conditioning Regimen ◽  
Complete Response ◽  
Phase Iii ◽  
High Dose ◽  
Cell Transplant ◽  
Red Marrow

Abstract Background: 166Ho-DOTMP is a beta-emitting radiophosphonate that localizes specifically to the bone surfaces and can deliver high dose radiation both to the bone and bone marrow. Follow-up data from 3 clinical trials with STR as conditioning for patients with MM undergoing autologous PBSCT are presented. Methods: In 2 Phase I/II dose-escalation trials, 83 patients received a dose of 166Ho-DOTMP STR calculated to deliver 20, 30, or 40 Gy to the red marrow; 82 pts received melphalan (140 or 200 mg/m2) ± 8 Gy TBI (n=25), followed by PBSCT. As of June, 2004, 77 subjects have been followed for at least 48 months. In a separate Phase II dosimetry trial, 12 patients received two 30 mCi tracer doses of 166Ho-DOTMP STR to determine the reproducibility of biodistribution and pharmacokinetics (PK). All pts received a 25 Gy therapy dose with concurrent IV hydration and continuous bladder irrigation, followed by 200 mg/m2 melphalan and PBSCT. These patients have been followed for at least 18 months. Results: Up to 2.3 Ci/m2, 166Ho-DOTMP STR was given in the Phase I/II trials; 29/83 (35%) patients achieved complete response (CR) and overall response rate (CR + PR) was 64% (7 pts not evaluable). The Kaplan-Meier estimate of median survival is 5.2 years for all 83 patients. In patients who are at least 4 years post transplant who achieved a CR, the survival is 74% (n=27). In patients who achieved less than a CR at least 4 years ago, the survival is 34% (n=44). Dose-related radiation-induced kidney toxicity presented in some patients more than 6 months post-therapy. The dose of 166Ho-DOTMP STR in the Phase II dosimetry trial was 550 to 860 mCi/m2, 166Ho-DOTMP. Currently, 18 months of follow-up reveals no occurrence of hemorrhagic cystitis or > Grade 2 elevated creatinine. A CR rate of 17% with an overall survival of 92%, was observed. In 10 patients who received 166Ho-DOTMP STR 750 mCi/m2 ± 10% in the Phase I/II trial, the CR rate was 40%, and the 4-year survival was 70%. Monitoring for safety and duration of response is ongoing in all 3 trials. Conclusion: Follow-up from the Phase I/II trials confirms that 166Ho-DOTMP STR provides favorable efficacy and safety as part of the conditioning regimen for patients with MM undergoing PBSCT. A Phase III, randomized multicenter study is now open to enrollment, comparing the safety and efficacy of 166Ho-DOTMP STR plus melphalan to melphalan alone as conditioning for PBSCT in subjects with primary refractory MM who have failed to respond to induction therapy, including high-dose dexamethasone, and are within 18 months of diagnosis.

Unrelated Donor Hematopoietic Cell Transplantation after Non-Myeloablative Conditioning for Patients with High Risk Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3158-3158
Author(s):  
Roberto Sorasio ◽  
Luisa Giaccone ◽  
Francesca Patriarca ◽  
Vittorio Montefusco ◽  
Stefano Guidi ◽  
...  
Keyword(s):  
Disease Progression ◽  
Initial Treatment ◽  
Response Rate ◽  
Treatment Plan ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Response ◽  
High Dose ◽  
Unrelated Donor

Abstract Allografting can induce long-term molecular remissions and possibly cure in myeloma patients. The recent development of non-myeloablative conditionings has reduced the transplant-related mortality (TRM) typically associated with myeloablation and extended the eligible age for transplantation. Moreover, high response rates are reported especially when allografting is preceded by cytoreductive high dose chemotherapy. We investigated the feasibility of unrelated donor non-myeloablative transplantation as either part of the initial treatment plan or as salvage treatment in heavily pre-treated patients. Twenty-two patients underwent non-myeloablative allografting, 10 as part of their initial treatment and 12 at disease relapse. Donors were matched for HLA-A, B, C, DRB1 and DQB1 by high-resolution typing. Only one single class I allele disparity was allowed. Conditioning regimen consisted of fludarabine 90 mg/m2 and 2 Gy total body irradiation. GVHD prophylaxis included oral cyclosporine (CyA) and mycophenolate mofetil (MMF). CyA was administered at 6.25 mg/Kg every 12 hours from day -3; levels were targeted to the upper therapeutic range (450–500 ng/ml, Abbott TDX, Abbott Park, IL) for the first month post-transplant. In the absence of GVHD, CyA was tapered from day +100 and discontinued on day +177. MMF was administered from day 0 after PBSC infusion to day +40 at 15 mg/Kg every 8 hours, and then tapered till day +96. Twenty/22 (91%) patients readily engrafted. Two patients experienced graft failure and eventually recovered autologous hematopoiesis. After a median follow up of 11 months (3–27), TRM was 18% and 16/22 patients (73%) are alive. Deaths occurred in 10% of patients transplanted upfront and in 42% of those transplanted at relapse: 3 patients died from infections, 1 from hemolytic uremic/ thrombotic thrombocytopenic purpura syndrome, and 2 from disease progression (both were transplanted at relapse). Ten/20 engrafted patients (50%) had grade II–IV acute GVHD (10% grade III–IV), and 59% had extensive chronic GVHD. Overall response rate was 60% (including 20% CR): 78% in patients transplanted upfront (no disease progression observed) and 45% in those transplanted at relapse. In the two groups, progression-free and one year event-free survival were 100% and 44% (p<0.025), and 90% and 28% respectively (p<0.005). Unrelated donor non-myeloablative allografting is feasible with relatively low TRM and high response rate. Graft-versus-myeloma effect appears to be more efficient when patients are treated soon after diagnosis. Longer follow-up is needed to assess response duration.

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