Longer Follow-Up Confirms a Low Relapse Rate after Non-Myeloablative Allogeneic Transplantation (NMT) for Non-Hodgkin’s Lymphoma (NHL), Including Patients with PET or Gallium-Avid Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 44-44 ◽  
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Ming-Sheng Lee ◽  
Grace-Julia Okoroji ◽  
Luis Fayad ◽  
...  
Keyword(s):  
Disease Progression ◽  
Relapse Rate ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Large Cell ◽  
Allogeneic Transplantation ◽  
Study Entry

Abstract We have used the combination of fludarabine/cyclophosphamide/rituximab (FCR) as a conditioning regimen for NMT in patients (pts) with relapsed NHL (Blood989:3595, 2001). Seventy-eight consecutive pts were treated. Median age was 53 yrs (range, 21–68). Median # of prior chemoregimens was 3. Twenty-one (27%) had failed a prior autologous. Histologies included follicular (FL)=47 pts (60%), diffuse large cell (DLCL)=16 pts (21%) and mantle cell (MCL)=15 pts (19%). Thirty-nine (50%) were in partial remission (PR), five (6%) had stable or progressive disease (SPD) and 34 (44%) were in complete remission (CR) at study entry. Sixty-nine (88%) had a matched sibling, 6 a matched unrelated, and three a mismatched sibling donor. Ten pts had either PET or Gallium-avid disease at transplant: six were in clinical PR and 4 were in SPD. Peripheral blood was the source of graft in 71 pts (91%). Tacrolimus/Methotrexate were used for GVHD prophylaxis. Median time for ANC >500 was 10 days. Sixty pts did not require any platelet transfusion. All but 2 pts who had SPD, converted to CR post transplant. All pts engrafted donor cells. Six had a secondary graft failure (GF), two of which occurred in the setting of disease progression. With a median follow-up time of 34 months (mos) (range, 3 to 70 mos), only 6 pts (8%) relapsed: two pts were in SPD/PET or Gallium(+), 3 were in PR/PET or Gallium(−) and one was in CR at transplant. None of the 6 pts who were PR/PET or Gallium (+) at study entry relapsed. Overall the risk of relapse in PET/Gallium (+) or (−) disease was not significant (P=0.15). Five pts received donor lymphocyte infusion (DLI) for disease progression: one achieved CR; the 4 other pts (two were in GF) did not respond. DLI was also given successfully to two other pts because of cytopenia related to a viral infection (1), and because of decreasing chimerism (1). Overall survival (OS) for all pts was 88%, 82% and 74% at 1,2 and 3-yr, respectively. By univariate analysis, OS was 95% at 3-yr for those who had failed a prior autologous transplant (P = 0.04). Patients with FL histology had also a better 3-yr survival than DLCL [88 % vs 51% (P = 0.008)]; the difference with MCL (65% at 3-yr) was not statistically significant (P = 0.2). Non-relapse related mortality was 11%, 13%, and 19% at 1, 2 and 3-yr, respectively. The incidence of acute II-IV GVHD was 17%. Patients with FL disease had lower incidence of acute II-IV and III-IV GVHD than DLCL [11% vs 31%, P = 0.04; and 2% vs 25%, P = 0.02; respectively] which may have contributed to the higher OS rate in FL. Both FL and DLCL pts had similar age and donor type distribution. Two pts developed chronic GVHD post DLI. The incidence of chronic extensive and limited GVHD was 51% and was not statistically different between various histologies. We conclude that NMT with FCR for NHL is an effective treatment even in pts who failed a prior autologous transplantation and is associated with a low incidence of acute GVHD. The lower than expected relapse rate observed may be indicative that NMT could be curative for these diseases.

Nonmyeloablative Allogeneic Transplantation (NMT) for Relapsed Follicular Lymphoma (FL): Continuous Complete Remission with Longer Follow-Up.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 485-485
Author(s):  
Issa F. Khouri ◽  
Rima M. Saliba ◽  
Martin Korbling ◽  
Chitra Hosing ◽  
Luis Fayad ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Time ◽  
De Novo ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Study Entry ◽  
Two Samples

Abstract NMT carries the promise of long-term disease control in FL by graft-versus-lymphoma immunity. We investigated the long-term efficacy of this strategy. Between March 1999 and April 2005, 47 consecutive patients were enrolled, ranging in age from 33 to 68 years (median, 53 years). The time from diagnosis to transplantation ranged from 7 months to 24 years (median, 3 years). All patients had recurrent chemosensitive FL. Each patient had received 2 to 7 (median, 2) chemotherapy regimens. Eight patients (17%) had failed a prior autologous transplantation. At the time of transplantation, 29 patients (61%) were in PR, and 18 (31%) were in CR. The conditioning regimen consisted of fludarabine (30 mg/m2 daily for 3 days), cyclophosphamide (750 mg/m2 daily for 3 days) and rituximab (Khouri, Blood 2001). This was followed by an infusion of HLA-matched hematopoietic cells from related (n=45) or unelated donors (n=2). Tacrolimus and methotrexate were used for graft-versus-disease (GVHD) prophylaxis. All patients achieved CR after transplantation. The median time to achieve CR in patients who had evidence of active disease at study entry was 5.5 months. Two relapses occurred. One was observed at 18 months; this patient responded to DLI with a continuous CR at 24+ months. The other patient who developed a relapse, was found to be simultaneously in graft failure 20 months after his transplantation. That patient was treated with rituximab and is still in CR at his last follow-up 4 years later. Eighteen patients had PCR evidence of bcl-2 translocation in the bone marrow at study entry. There were a total of 100 bone marrow post-treatment PCR samples available for analysis. Ninety eight samples that are drawn at a median time of 45 months after transplantation (range 4 months to 72 months) showed a negative PCR result. Two samples from 2 different patients were PCR-positive early after transplant; they became PCR-negative 3 months later. With a median follow-up time of 56 months (range, 19–94 months), the estimated overall survival (OS) and current progression-free survival (CPFS) rates at 6 years were 85% (95% confidence interval [CI], 71%–93%) and 83% (95% CI 69%–91%), respectively. The incidence of acute grade II–IV GVHD was 11% (95% CI, 31%–66%). The incidence of chronic extensive and limited GVHD, was 51% (95% CI, 44%–78%). Of the 28 patients who developed chronic GVHD, 20 (71%) had a de novo onset. The median time of onset of chronic GVHD was 262 days after transplantation, and the OS of patients with chronic GVHD was 89%, with a median follow-up time of 57 months (range, 19–94 months). Only five patients of the whole study group are still receiving immunosuppressive therapy at the time of their last follow-up. In conclusion, the longer follow-up of our study does provide further insight into long-term disease activity and regimen toxicity of NMT for FL, laying the groundwork for prospective comparative trials. We believe that the described results are a step forward toward finding a cure for this disease.

Favorable Long-Term Survival After Reduced-Intensity Allogeneic Transplantation for Multiple-Relapse Aggressive Non-Hodgkin's Lymphoma

2009 ◽  
Vol 27 (3) ◽  
pp. 426-432 ◽  
Author(s):  
Kirsty J. Thomson ◽  
Emma C. Morris ◽  
Adrian Bloor ◽  
Gordon Cook ◽  
Don Milligan ◽  
...  
Keyword(s):  
Treatment Failure ◽  
Chronic Gvhd ◽  
Autologous Transplantation ◽  
B Cell Lymphoma ◽  
Allogeneic Transplantation ◽  
Published Data ◽  
Term Survival ◽  
Experienced Treatment ◽  
Reduced Intensity

Purpose The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, with relatively little published data. We report the outcome of reduced-intensity transplantation (RIT) in a cohort of 48 consecutive patients with relapsed/refractory DLBCL (30 patients with de novo disease and 18 patients with transformed follicular lymphoma) who underwent transplantation with an alemtuzumab-containing regimen, with a median follow-up of 52 months. Patients and Methods Patients had experienced treatment failure with a median of five lines of prior therapy, including autologous transplantation in 69%, and 17% of patients were chemotherapy refractory at transplantation. Median age was 46 years, and 38% of patients had matched/mismatched unrelated donors. Conditioning was with alemtuzumab, fludarabine, and melphalan, and additional graft-versus-host disease (GVHD) prophylaxis was with cyclosporine. Results All patients were successfully engrafted. Only 17% of patients developed grade 2 to 4 acute GVHD, with 13% experiencing extensive chronic GVHD. Four-year estimated nonrelapse mortality was 32%, and relapse risk was 33%. Twelve patients received donor lymphocyte infusions ± chemoimmunotherapy for relapse, and five patients obtained durable remissions, giving current progression-free survival (PFS) and overall survival (OS) rates at 4 years of 48% and 47%, respectively. Patients who had chemotherapy-sensitive disease before RIT had current PFS and OS rates at 4 years of 55% and 54%, respectively. Chemotherapy-refractory patients had a poor outcome. Conclusion The encouraging survival rates with extended follow-up suggest a role for RIT in chemotherapy-sensitive relapsed DLBCL, even in patients who have previously experienced treatment failure with autologous transplantation. Future studies will be required to determine whether any subset of patients with relapsed DLBCL should be considered for RIT versus autologous transplantation.

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 < 500/μl and platelets < 50/μl for a median of 0 days. Engraftment was prompt with 90 % of patients having achieved > 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.

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.

Late Relapses Characterize Autologous Transplantation (ASCT) in First Complete Remission (CR) for Peripheral T-Cell Lymphoma (PTCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 5110-5110 ◽  
Author(s):  
Tarun Kewalramani ◽  
Steve Horwitz ◽  
Andrew D. Zelenetz ◽  
Stephen D. Nimer ◽  
Craig H. Moskowitz
Keyword(s):  
T Cell ◽  
Median Time ◽  
Progressive Disease ◽  
Cell Lymphoma ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
T Cell Lymphoma ◽  
Time To Progression

With the exception of ALK-positive anaplastic large cell lymphoma (ALCL), standard-dose chemotherapy is curative in a minority of patients (pts) with PTCL, and most pts have progressive disease less than 2 years from completing treatment. Several studies suggest that ASCT in 1st CR significantly improves the short-term outcome of pts with PTCL, but its long-term efficacy is not known. To address this, we assessed the outcome of sequential patients who underwent ASCT in 1st CR (n=15). Histologic subtypes were PTCL, unspecified, in 6 pts, angioimmunoblastic T-cell lymphoma in 5 pts, ALK-negative ALCL in 3 pts and hepatosplenic gamma delta T-cell lymphoma in 1 pt. Induction chemotherapy was CHOP (n=2) or CHOP-ICE hybrid (n=12) in 93% of pts. The age-adjusted IPI (AAIPI) was 2–3 in 9 of 14 assessable patients (64%), and 11 pts (73%) had stage III–IV disease. The conditioning regimen consisted of BEAM or CBV in 10 pts and TBI/Cy/VP-16 in 5 pts. All patients received peripheral blood progenitor cells for hematopoietic support. The median follow-up of all patients is 24 months (range 4.5–70). Five pts (33%) have progressed, with a median time to progression of 50 months (range 10–70). Four of the 5 pts who progressed did so more than 2 years from ASCT; they comprise 57% of patients with more than 2-years of follow-up. Four of 5 patients with progressive disease have died, with a median time from progression to death of 1 month (0.6–14.6). In this small series the AAIPI was not predictive of PFS or OS. While our results confirm the that ASCT in 1st CR significantly delays the time to progression, they suggest that it may not be curative in the majority of patients. If confirmed in ongoing larger prospective studies, this observation warrants trials of post-ASCT maintenance treatment and, for younger patients, trials of allogeneic transplantation in 1st CR or sequential ASCT followed by allogeneic transplantation. Figure Figure

Allogeneic Stem Cell Transplantation for Multiple Myeloma: Possible Role in the Treatment.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3133-3133
Author(s):  
Liisa Volin ◽  
Heli Uotinen ◽  
Riitta Niittyvuopio ◽  
Eeva Juvonen ◽  
Anne Nihtinen ◽  
...  
Keyword(s):  
Disease Progression ◽  
Low Dose ◽  
Autologous Transplantation ◽  
Significant Proportion ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Unrelated Donor ◽  
Post Transplantation ◽  
Significant Difference

Abstract Abstract 3133 The treatment of multiple myeloma (MM) has been rapidly evolving with the introduction of new drugs, but this disease is still regarded as incurable, with few exceptions. The role of allogeneic stem cell transplantation in the treatment of MM is unclear at present. It offers the possibility to harness the curative potential of the graft-versus-myeloma effect, but high transplant-related mortality, as previously reported, has limited its use. We report our single-center experience of 120 patients treated with allogeneic transplantation at the Helsinki University Central Hospital since the year 2000 showing low transplant-related mortality and a significant proportion of patients achieving prolonged progression-free survival. The median age of the patients was 50 (range 28–65) years. Sixty-three patients were male, 57 female. The immunoglobulin classes were IgG 75, IgA 16, IgD 3, and light chain 26. Forty-nine patients received a myeloablative (MA) conditioning, 71 patients a reduced intensity conditioning (RIC). The MA regimens were cyclophosphamide 120 mg/kg + fractionated TBI 12 Gy, lungs 10 Gy (n= 30) and treosulfan 42 g/m2 + fludarabine 150 mg/m2 (n= 19), the RIC regimens TBI 2 GY (n= 52) or treosulfan 36 g/m2 (n= 19) with fludarabine. In 43 cases allotransplantation, conditioned with low-dose TBI-based regimen, was performed in a preplanned combination with autologous transplantation which preceded the allotransplantation with the median of 5 (range 2–8) months. Overall, 79 patients had an autologous transplantation in their previous history. The number of chemotherapy lines preceding allogeneic transplantation was 1 in 49, 2 in 30, and 3–7 in 41 cases. The median time from the diagnosis of MM to allotransplantation was 10 (range 5–82 ) months in transplantations with MA conditioning and 16 (7–170) months in those with RIC. Of the donors 74 were HLA-matched siblings and 46 unrelated. The graft was from peripheral blood in 99 and from bone marrow in 21 cases. In transplantations with low-dose TBI based conditioning the GVHD prophylaxis consisted of CsA and MMF. The other patients received CsA + MTX, in sibling transplantations with TBI-based MA conditioning added with methylprednisolone. ATG was given in transplantations from an unrelated donor except to patients conditioned with low-dose TBI. The state of the disease preceding the allotransplantation was the following: CR 18 (15 %), VGPR 7 (6 %) PR 82 (68 %), MR 3 (3 %), and progression 10 (8 %). At 100 days post-transplantation 30 patients (25 %) were in CR, 6 (5 %) in VGPR, 63 (53 %) in PR, 2 (2 %) in MR; 2 (2 %) had no change, and 13 (11 %) progressed. Five patients had died. The best response, achieved at the median of 3 (range 0 – 80) months post-transplantation, was CR 53 (44 %), VGPR 6 (5 %), PR 48 (40 %), MR 1 (1 %), NC 2 (2 %), and progression 10 (8 %). The median follow-up of living patients was 62 (range 1–140) months. The cumulative incidence of grade II-IV acute GVHD was 29 %; that of chronic GVHD 65 % (extensive 25 %) in MA transplantations and 80 % (extensive 51 %) in RIC transplantations. Seventy-three patients had disease progression; the cumulative incidence of progression until 10 years was 70%. There was no significant difference in the incidence of progression between MA and RIC transplantations. Thirty-six patients received DLI for the treatment of progression. Fifty-three patients have died, 38 of them in disease progression, and 15 of non-relapse causes. The cumulative incidences of non-relapse mortality (NRM) in MA and RIC transplantations were 0 vs. 3 % at 100 days, 2 vs. 9 % at 1 year and 8 vs. 26 % at 5 years. The survivals of MA and RIC patients were 92 vs. 87% at 1 year, 87 vs. 72% at 2 years, 64 vs. 56% at 5 years, and 49 vs. 35% at 10 years, respectively. The proportion of the whole patient population surviving without disease progression was 26% from 7 years on until the end of follow-up. There was no significant difference in the survival between transplantations from sibling and unrelated donor. In conclusion, the low NRM, particularly in transplantations with myeloablative conditioning, and the significant proportion of patients with long-term progression-free survival suggest a role for allogeneic transplantation in the treatment of myeloma. The optimal combination of modern drug treatment with allogeneic transplantation providing graft-versus myeloma effect should be assessed in clinical trials. Disclosures: No relevant conflicts of interest to declare.

Campath-IH Combined with Fludarabine/Cyclophophamide/Rituximab (FCR) as Conditioning for Unrelated Non-Myeloablative Hematopoietic Transplantation (NMT) for Non-Hodgkin’s Lymphoma (NHL): Low Mortality Rate and Lower Than Expected Incidence of Cytomegalovirus (CMV) Reactivation.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2902-2902
Author(s):  
Issa F. Khouri ◽  
Jeffrey J. Tarrand ◽  
Grace-Julia Okoroji ◽  
Rima M. Saliba ◽  
Chitra M. Hosing ◽  
...  
Keyword(s):  
Disease Progression ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Unrelated Donor ◽  
Positive Serology ◽  
Hematopoietic Transplantation ◽  
Cmv Reactivation

Abstract Graft-versus-host disease (GVHD) remains a significant cause for morbidity following unrelated hematopoietic transplantation. We investigated the addition of Campath-IH in vivo, at a total dose of 45 mg, to the FCR conditioning regimen for unrelated NMT for relapsed chemosensitive NHL. 25 consecutive patients (pts) with various lymphoid histologies {Follicular = 9, Mantle cell = 7, Large cell =9}were treated. Median age was 52 yrs (range, 31–64). Median # of prior chemoregimens received was 3, and 5 pts (20%) had failed a prior autologous transplant. Ten pts (40%) were in complete remission, and 15 (60%) had evidence of active disease at study entry. Pts received rituximab at 375 mg/m2 on day −8, −1, +6 and +13. Campath-IH 15 mg/iv was given daily on days −4,−3,−2. Chemotherapy was provided on the same days as the Campath-IH and consisted of fludarabine 30 mg/m2/day x 3, and cyclophosphamide 1000 mg/m2 /day x 3. Transplantation was given on day 0. Bone marrow was the source of graft in 20 pts (80%), and 5(20%) received peripheral blood. Tacrolimus (maintained at a low trough level of 5) and methotrexate were used as additional GVHD prophylaxis. Median time to recovery of an ANC&gt;500 was 11 days (range, 9–21). Nine pts (36%) did not require any platelet transfusions. All pts engrafted donor cells (median 81%, at 30 days); 19 pts remained mixed chimera at the time of their last follow-up. Five pts required donor lymphocyte infusion (DLI) for disease progression: 3 achieved complete, one partial and one had no response. With a median follow-up time of 16 mos (range, 3–45 mos), overall survival was 90% (95%CI, 66–99), and the current progression-free survival rate was 68% at 18 mos. Acute GVHD occurred in one pt (grade 1) pre-DLI, and in 3 pts (one grade 1, one grade 2, and one grade 3) post DLI. Chronic extensive GVHD occurred in 3 pts pre-, and 2 additional pts post DLI. Two pts died: one of chronic GVHD, and one of disease progression. Seventeen of the 25 transplants had either the recipient or the donor with CMV-positive serology. CMV prevention consisted of a once daily dose of foscarnet, and twice-weekly screening using the CMV Direct Antibody Fluorescent Stain Antigenemia test. With this strategy, only 9 pts (36%) had evidence of CMV reactivation (defined as any detection of CMV cells). No pt developed or died from CMV disease. These data suggest that unrelated NMT after Campath-FCR conditioning is associated with a low incidence of GVHD and treatment-related mortality. Foscarnet prevention with bi-weekly CMV screening is associated with a lower than expected risk for CMV reactivation. The regimen is a promising approach for unrelated donor transplantation for patients with advanced lymphoma.

Myeloablative Conditioning of Patients with Myelofibrosis with Myeloid Metaplasia Using i.v. Treosulfan and Autologous Peripheral Blood Progenitor Cell Transplantation (PBPCT) with High Doses of CD34+ Cells Results in Hematologic Responses - 32 Months Follow-Up of Three Patients and Short-Term Results of a New Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5515-5515
Author(s):  
Stefan Fruehauf ◽  
Eike C. Buss ◽  
Julian Toplay ◽  
Hans H. Kreipe ◽  
Anthony D. Ho
Keyword(s):  
Multicenter Study ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Allogeneic Transplantation ◽  
High Dose ◽  
Post Transplantation ◽  
Myeloid Metaplasia ◽  
Cd34 Cells ◽  
Myelofibrosis With Myeloid Metaplasia

Abstract Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder. Myeloablation with high-dose treosulfan and autologous PBPCT provides a palliative approach. A minimum of 5 x 106 CD34+ cells/kg was collected in all patients after G-CSF-priming (16 μg/kg/d for 4 days). Myeloablation consisted of treosulfan (total dose 42 g/m2). To date we have transplanted 3 patients, all female on an individual basis. We observed a prolonged time to reconstitution of leucocytes &gt; 1/nl post transplantation of 28 days (#1, #2) and 38 days (#3). The observation period post transplantation is 32 months now. Patient #1, who required erythrocyte transfusions twice weekly pretransplant received her last erythrocyte transfusion on day 56; her last Hb-value is 9.5 g/dl. The second patient (#2) recovered to platelet counts higher than pre transplantation (58/nl) at 3 months (143/nl) and had 125/nl at last follow-up. Pat. #3 showed a marked reduction of max. spleen size and a rise in Hb from 9 g/dl to 12 g/dl after 12 months, the last Hb value at 26 months was 7.6 g/dl and she received about 3 erythrocyte transfusions per month again. She then underwent allogeneic transplantation from her sister and is currently alive and well. Three male patients were treated in a new one-armed, multicenter study applying the aforementioned protocol. In two patients we observed again a prolonged reconstitution period of 28 (S1) and 44 (S2) days. In one patient (S1) leukocytosis and thrombocytosis resolved while transfusion dependent anemia persisted. In the second patient (S2) transfusion dependent anemia persisted. He received a backup transplantation but still remains transfusion-dependent. Patient S3 had a critical thrombocytopenia of 16/nl before transplantation and proved to be refractory to thrombocyte transfusions post-transplantation. He developed cerebral hemorrhage and died. The conditioning regimen was well tolerated and despite the prolonged aplasia period neutropenic fever was rare (median 1 day, range 0–6 days). The overall response rate was 60%, the mortality rate was 17% which is both compatible with previous data of autologous transplantation in MMM patients undergoing busulfan conditioning. This multicenter study is continuing to recruit patients (http://leukaemie.krebsinfo.de/kn_home/Studien/studie_101.html).

Stem Cell Transplantation (SCT) for Acute Myeloid Leukemia (AML): A Single Center in over 25 Years Experience.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5351-5351
Author(s):  
Stella Santarone ◽  
Erminia Di Bartolomeo ◽  
Paolo Di Bartolomeo
Keyword(s):  
Stem Cell ◽  
Multiorgan Failure ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Stem Cell Source ◽  
Short Course ◽  
Gvhd Prophylaxis

Abstract In this study we report the results of SCT in 116 patients (M51, F65) with AML transplanted from HLA identical (n=111) or 1 antigen mismatched (n=5) related donors between 1981 and 2006. The median age was 33 years (1–63). At time of SCT, 76 patients were in CR1, 23 in CR2 and 17 in CR>2 or in relapse. The stem cell source was bone marrow for 94 patients, PBSC for 21 and cord blood for 1. The conditioning regimen was myeloablative for 110 patients (BU CY for 87 and TBI CY for 23) and not-myeloablative for 6 (Thiotepa CY). For GvHD prophylaxis, 30 patients received cyclosporine (CSA) alone and 86 were given CSA and short course methotrexate. All patients engrafted with a median time to achieve 0.5 ×109/L neutrophils and 50×109/L platelets of 20 (10–37) and 22 (11–103) days respectively. One patients lost the graft six months after SCT and was successfully retransplanted. Acute GvHD grade II–IV occurred in 24%. Chronic GvHD occurred in 21% (9% limited, 12% extensive). The overall transplant related mortality (TRM) was 15.5% at 12 months (14,4% in CR1, 8,7% in CR2 and 29% in CR>2 or in relapse). Causes of death were: GvHD in 6 patients, infection in 6, multiorgan failure in 3, renal insufficiency in 1, encephalopathy in 1, pancreatitis in 1. The overall incidence of relapse was 29% (25% in CR1, 26% in CR2, 53% in CR>2). Twelve patients (1 in CR1, 5 in CR2 and 6 in >CR2 or relapse) underwent a second SCT from the same donor after a median interval from the first and second SCT of 456 (203–1946) days. The TRM post-second SCT was 16%. Nine of 12 patients are now living and cured after a median follow-up of 5,4 years (1–16,8). Overall, after a median follow-up of 8.08 (0.3–22) years, 71 out of 116 patients (61%) are living and cured. The 20 years probability of disease free survival is 68% for patients in CR1, 74% for patients in CR2 and 18% for patients in CR>2 or relapse (Fig. 1). In univariate analysis the patient age < 30 years, the BUCY regimen as compared to the TBI regimen and a dose of marrow cells > 3.0 × 108/Kg are associated with a better survival. We conclude that SCT is a curative treatment for patients with AML. In our experience second SCT gives results comparable to those of first transplant. Fig 1. Probability of DFS according to phase of disease at SCT Fig 1. Probability of DFS according to phase of disease at SCT

Reduced Intensity vs Myeloablative Conditioning for HLA Matched Sibling Transplantation in Follicular Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 656-656 ◽  
Author(s):  
Koen Van Besien ◽  
Jeanette Carreras ◽  
Mei-Jie Zhang ◽  
Julie Vose ◽  
Hillard Lazarus ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Chronic Gvhd ◽  
Univariate Analysis ◽  
Autologous Transplantation ◽  
Conditioning Regimen ◽  
Poor Performance Status ◽  
P Value ◽  
Increased Risk ◽  
Conditioning Regimens ◽  
Reduced Intensity

Abstract Several new reduced intensity conditioning regimens are being investigated for allogeneic transplantation. To evaluate their effects in follicular lymphoma, we studied outcome of HLA-identical sibling transplants in 205 recipients reported to the CIBMTR between 1997 and 2002. Only patients without prior allogeneic or autologous transplantation were included. Twenty-seven patients (13%) had follicular large cell (grade III) lymphoma; the remaining had grade I or II disease. 27% had chemotherapy-resistant disease and 32% had poor performance status prior to transplantation. Conditioning regimens were categorized as myeloablative (ABLAT; n=120) or reduced intensity (RIC; n=85). ABLAT was defined as total body irradiation (TBI) containing regimens with single fraction of ≥500 cGy, fractionated doses of ≥ 800 cGy, busulfan doses &gt;9 mg/kg or melphalan doses &gt;150 mg/m2. We defined RIC as TBI doses &lt;500 cGy, busulfan doses &lt;9 mg/kg, melphalan doses of ≤150 mg/m2 and fludarabine regimens without busulfan or melphalan. 70% of ABLAT was TBI based; 24% was busulfan-cyclophosphamide. Melphalan based regimens were used in 23% of RIC, reduced dose busulfan in 21%, fludarabine-cyclophosphamide in 41% and low dose TBI in 7%. RIC constituted fewer than 10% of transplants reported in 1997, about 50% in 2000 and 80% in 2002. Median recipient age was 45 y (28–70y) for ABLAT vs. 50 y (27–67y) for RIC (p&lt;0.001). Median time from diagnosis to transplant was 24 mo for ABLAT vs. 34 mo for RIC (p=0.001). PBSC was used for 65% of ABLAT but 92% of RIC (p&lt;0.001). GVHD prophylaxis included a calcineurin antagonist in all patients, but was combined with MTX in 86% of ABLAT compared to 54% of RIC (p&lt;0.001). Median follow-up of survivors was 49 mo for ABLAT vs. 36 mo for RIC (p=0.004). In univariate analysis, there were no differences in acute or chronic GVHD, treatment-related mortality (TRM), progression-free survival (PFS) or overall survival (OS) between the two groups. The median hospital stay was slightly shorter for RIC vs. ABLAT (25 vs. 28 days, p=0.05), and there was a trend toward an increased risk of disease recurrence after RIC (p=0.09). Forty ABLAT recipients and 30 RIC recipients have died. Eleven of 40 deaths with ABLAT transplant vs 2 of 30 with RIC were attributed to organ failure (p=0.03); 5 and 4 deaths, respectively, were attributed to GVHD (p=NS), and 8 and 11 deaths, respectively, to relapse (p=NS). In multivariate analysis, performance score and chemotherapy sensitivity were independently associated with TRM, OS and PFS, but conditioning regimen was not. There was a trend for increased risk of recurrence after RIC (RR=1.91; p=0.09). In summary, RIC is now, by far, the most common approach for allotransplantation in follicular lymphoma. In this analysis, TRM, GVHD, OS and PFS after RIC are similar to ABLAT. Outcomes ABLAT (%) RIC (%) P-value 30 day mortality 8 (3–13) 6 (2–12) 0.64 100 day mortality 19 (13–27) 15 (8–24) 0.46 Acute GVHD @ 100 days, grades (2–4) 37 (28–46) 40 (30–51) 0.62 Chronic GVHD @ 1 year 44 (34–53) 53 (42–64) 0.20 TRM @ 1 year 23 (16–31) 20 (12–29) 0.57 TRM @ 3 years 25 (18–24) 24 (16–24) 0.83 Progression/Relapse @ 1 year 8 (4–14) 17 (9–25) 0.09 Progression/Relapse @ 3 years 9 (5–15) 21 (13–31) 0.03 PFS @ 1 year 68 (60–76) 63 (53–73) 0.47 PFS @ 3 years 65 (56–74) 55 (44–66) 0.14 OS @ 1 year 72 (64–80) 72 (62–81) 0.90 OS @ 3 years 70 (61–77) 64 (53–74) 0.40

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