Hematopoietic cell transplantation (HCT) after low-dose, total body irradiation-based regimen increased leukemia-free survival (LFS) in elderly patients with cytogenetic high-risk AML compared to chemotherapy (OSHO 97 study)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7003-7003
Author(s):  
D. Niederwieser ◽  
C. Becker ◽  
R. Krahl ◽  
H. Al-Ali ◽  
T. Lange ◽  
...  
Keyword(s):  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Consolidation Chemotherapy ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Transplant Patients ◽  
Total Body ◽  
Worse Prognosis ◽  
Related Mortality

7003 Background: Even after reaching initial CR, most AML patients > 60 years relapse within 2 years of diagnosis. Cytogenetic high risk AML (abn 3q26, abn 11q23, -5/5q-, -7/7q- and complex) has an even worse prognosis. Attempts to improve survival by intensifying consolidation chemotherapy have so far failed. We investigated the role of allogeneic HCT in comparison to chemotherapy among patients with high risk cytogenetics entered into the OSHO AML 97 protocol. Methods: Initial treatment consisted of a course of induction therapy (AraC 2 g/m2 iv on day 1,3,5,7 + mitoxantrone 10 mg/m2 iv day 1 –3, repeated once in case of PR) followed by one consolidation course (AraC 240 mg/m2 iv day 1 –5 + mitoxantrone 10 mg/m2 iv day 1 –2). Patients in CR1 after the consolidation I were either treated with an additional consolidation therapy or with an allogeneic HCT from related (n=2) or unrelated (n=10) donors. Transplant patients were conditioned with fludarabine and TBI 200 cGy and immunosuppressed with cyclosporine and mycofenolate mofetil. Results: A total of 347 patients are evaluable. Of 105 (33%) patients with high-risk cytogenetics, 53 (50%) went into remission after one or two cycles of induction chemotherapy. Of these 53 patients, 42 received consolidation I and 35 patients were available for either consolidation II (n=23) or HCT (n=12). Median age of the patients receiving chemotherapy was 64 (range 61–77) years and that of the transplant patients was 64 (range 61–68) years. LFS at 4 years was 42 ± 14% after HCT and 15 ± 8% after chemotherapy. Major differences in relapse incidences were seen between the two groups, with the lowest RI at 4 years after HCT (36 ± 15%) followed by chemotherapy (85±8%, p<0.04). Treatment related mortality at 4 years was 35±17% and 0±0% for patients receiving HCT and chemotherapy, respectively (p<0.05). Conclusions: From these results, we conclude that consolidation with allogeneic HCT after minimal conditioning is superior to chemotherapy even in older patients with high risk cytogenetics. While differences in TRM were seen between the treatment arms, a lower relapse incidence after related and unrelated HCT contributed to the improved LFS. No significant financial relationships to disclose.

Increased Leukaemia Free Survival (LFS) in Patients with Cytogenetic High Risk AML after Related or Unrelated Hematopoietic Cell Transplantation (HCT) Compared to Chemotherapy in the OSHO 96 and 2002 Studies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 264-264
Author(s):  
Dietger Niederwieser ◽  
Cornelia Becker ◽  
Rainer Krahl ◽  
Haifa-Kathrin Al-Ali ◽  
Simone Heyn ◽  
...  
Keyword(s):  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Young Patients ◽  
Consolidation Therapy ◽  
Multicenter Studies ◽  
Allogeneic Hct ◽  
Dismal Prognosis ◽  
Unrelated Donors ◽  
Total Body

Abstract Cytogenetic high risk AML (abn 3q26, abn 11q23, −5/5q-, −7/7q- and complex) has a dismal prognosis with a two year overall survival (OS) below 20% even in young patients. Attempts to improve survival by intensifying consolidation chemotherapy have so far failed. In the two OSHO protocols AML 96 and AML 2002, we investigated the role of allogeneic HCT in these patients. A total of 708 patients have been entered into the two studies between 1997 and the present. The first protocol (AML 96) compared two different schedules employing identical total dosages of intermediate AraC and Idarubicin. The second protocol (AML 2002) studied the role of two different induction therapies in patients failing to reach CR after the first induction therapy. In patients with cytogenetic high risk AML, the search for a donor (either familial or, if none available, then unrelated) was initiated as soon as possible. Allogeneic HCT was scheduled either after induction or after first consolidation therapy. HCT was performed after conditioning with cytoxan and 1200 cGy total body irradiation followed by GvH-D prophylaxis with cyclosporine and methotrexate. Of the 708 patients, 138 (19,5%) had high risk cytogenetics and 77 (55,8%) of these went into remission after one or two cycles of induction chemotherapy. Of these 77 patients, 54 were alive and in CR after the first consolidation therapy and were allocated to either related (n=12) or unrelated (n=21) HCT or, if no compatible donor was available, to a two courses of chemotherapy (n=21). Median age of the patients was 36 (range 17–51) years, 46 years (range 23–59) years and 49 (range 16–60) years for patients receiving related HCT, unrelated HCT and chemotherapy respectively. Data were analysed as intention to treat.LFS at 3 years was 67 ± 14% after related and 44 ± 14 % after unrelated HCT, but decreased to 11 ± 7% in patients receiving chemotherapy. Allogeneic HCT results were significantly better than the results of chemotherapy with p-values of 0.005 and 0.002 for related vs. chemotherapy and unrelated vs. chemotherapy respectively. Major differences in relapse incidences were seen between the three groups, with the lowest RI at 3 years after related HCT 26±0.13%, followed by unrelated HCT 48±15% and by chemotherapy 89±8% (p=0.003 and p=0,0006 for chemotherapy vs. related or unrelated HCT). Transplant related mortality at 3 years was 10±9%, 14±10% and 6±6% for patients receiving HCT from related donors, from unrelated donors and chemotherapy, respectively. Conclusions: From the results observed in the two prospective, multicenter studies we conclude that consolidation with allogeneic HCT is superior to chemotherapy in younger patients with high risk cytogenetics. While no differences in TRM were seen between the three treatment arms, a lower relapse incidence after related and unrelated HCT contributed to the improved OS.

A Regimen of Treosulfan and Fludarabine Followed by Allogeneic Hematopoietic Cell Transplantation (HCT) for High-Risk Hematologic Malignancies Is Associated with Low Treatment-Related Mortality

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2994-2994 ◽  
Author(s):  
Eneida R. Nemecek ◽  
Mohamed L. Sorror ◽  
Kristine C. Doney ◽  
Bart Lee Scott ◽  
Tibor J. Kovacsovics ◽  
...  
Keyword(s):  
High Risk ◽  
Hematologic Malignancies ◽  
Free Survival ◽  
Allogeneic Hct ◽  
Number Of Patients ◽  
Significant Difference ◽  
First Remission ◽  
Comorbidity Index ◽  
Risk Categories ◽  
Related Mortality

Abstract Allogeneic HCT has the potential of curing high-risk hematologic malignancies, but intensive preparative regimens are associated with a significant risk of regimen-related toxicity and transplant-related mortality (TRM). Treosulfan is an alklyating agent with predictable inter- and intra-patient pharmacokinetics after IV administration. We conducted a dose optimization study of treosulfan in combination with fludarabine as conditioning regimen for allogeneic HCT in patients with acute myeloid (AML) or lymphoblastic leukemia (ALL) or myelodysplastic syndrome (MDS). The optimal treosulfan dose was determined by the incidence of severe/fatal regimen-related toxicity, graft failure and TRM. Sixty patients, 5–60 (median 46) years of age, with AML in first remission (n=26), AML in second remission (n=9), AML in relapse (n=9), ALL in second remission (n=3) or advanced MDS (n=13) were treated. Disease classification by CIBMTR risk categories was standard (n=26), intermediate (n=12) and advanced (n=22), with 63% of patients considered at high risk for relapse due to disease beyond first remission, treatment-induced malignancies or history of previous HCT. The majority of patients were considered at high risk for TRM with conventional transplant regimens for several reasons including: secondary (treatment-related) malignancy (n=12), previous HCT (n=8) or comorbid conditions. Comorbidity index (HCT-CI) was 0–7 (median 2); 50% of patients in first remission and 44% of patients in second remission or with more advanced disease had scores of 3 or higher. Patients received treosulfan at a dose of 12 g/m2/day (first 5 patients) or 14 g/m2/day (n=55) on days −6 to −4, and fludarabine (30 mg/kg/day) on days −6 to −2. Graft-versus-host disease (GVHD) prophylaxis was with tacrolimus (n=58) or cyclosporine (n=2) combined with methotrexate. Stem cell source was either from an HLA-matched sibling (n=30) or matched unrelated donor (n=30), and included bone marrow (n=7) or filgrastim-mobilized peripheral blood stem cells (n=53) on day 0. All evaluable patients engrafted, with a neutrophil count ≥500 reached by 5–30 (median 18) days. Acute GVHD occurred in 34 of 55 evaluable patients (CIBMTR grade A in 9 patients, grade B in 22, and grade C in 3 patients). Chronic GVHD occurred in 22 of 54 patients surviving beyond day 80 (limited in 12 and extensive in 10 patients). Dose limiting toxicity was observed in 2 patients (mucositis requiring intubation and acute renal failure, respectively). Forty-three patients are alive, with a follow-up of 2–32 (median 13) months. Day–100 mortality was 10%. Estimated one-year overall and disease-free survival, relapse and TRM were 69%, 61%, 34% and 8%, respectively. Event-free survival for patients considered at high risk for relapse was significantly lower than for the remaining patients (44% vs. 81%; HR= 0.27, 95% CI 0.15–0.78, p=0.01). There was no significant difference in TRM across groups defined by disease category. The following table summarizes outcomes by CIBMTR disease risk categories and comorbidity index: Number of patients 1 Standard: AML CR1, Intermediate: AML/ALL CR2, Advanced: all others. 2 6 of 26 patients with AML in CR1 had treatment-induced leukemia. Risk category 1 Total DFS TRM Relapse Standard 2 26 17 0 9 Intermediate 12 7 2 3 Advanced 22 13 2 7 HCT-CI &lt; 3 32 20 1 11 HCT-CI ≥ 3 28 17 3 8 In summary, treosulfan plus fludarabine is a well-tolerated regimen with promising disease control and low rates of toxicity and TRM in high-risk patients with acute leukemia and MDS. Further studies of this regimen in more homogeneous cohorts of patients are warranted.

The results of multicenter phase II, double-blind placebo-controlled trial of maintenance ixazomib after allogeneic hematopoietic cell transplantation (alloHCT) for high-risk multiple myeloma (MM) from the Blood and Marrow Transplant Clinical Trials Network (BMT CTN 1302).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7003-7003
Author(s):  
Taiga Nishihori ◽  
Qaiser Bashir ◽  
Marcelo C. Pasquini ◽  
Michael Martens ◽  
Juan Wu ◽  
...  
Keyword(s):  
High Risk ◽  
Hematopoietic Cell Transplantation ◽  
Controlled Trial ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Progression Free Survival ◽  
Double Blind ◽  
Allogeneic Hct ◽  
Reduced Intensity ◽  
Related Mortality

7003 Background: The role of alloHCT and subsequent maintenance for the treatment of high-risk MM has not been fully defined. We evaluated the efficacy of ixazomib maintenance therapy after alloHCT using reduced intensity fludarabine/melphalan/bortezomib (Flu/Mel/Bort)-based conditioning regimen to treat patients with high risk MM. Methods: This phase 2 prospective multicenter trial (NCT#02440464) enrolled adults 70 years or younger, with either high-risk MM defined by cytogenetics or plasma cell leukemia (PCL) or relapse within 24 months after autologous HCT. Conditioning regimen consisted of Flu/Mel/Bort. Patients received HLA-matched donor unmanipulated peripheral blood grafts. Graft-versus-host disease (GVHD) prophylaxis was tacrolimus plus methotrexate. Between days +60 and +120 after allogeneic HCT, patients were randomly assigned (1:1, stratified by number of prior progressions) to receive ixazomib at 3 mg orally on days 1, 8, 15 on a 28-day cycle or matching placebo for 12 cycles. The study aimed to enroll 138 patients with 110 patients achieving randomization for a progression-free survival (PFS) comparison ixazomib maintenance vs. placebo. Results: Fifty-seven patients from 15 centers were enrolled (2015-18), of whom 52 (91.2%) received allogeneic HCT, and 43 (82.7%) proceeded to randomization (21 assigned to ixazomib and 22 to placebo). Enrollment was delayed by a clinical hold after enrollment of 17 patients due to toxicity concerns related to the conditioning regimen. Remaining patients were enrolled after an amendment reduced bort to a single pre-HCT dose. These and other delays in enrollment led to premature study closure. Median age was 56 (range, 35-65) years, and 33 patients (57.9%) had high-risk MM with 9 patients (15.8%) with primary PCL. At 24 mo post alloHCT, PFS and OS among all alloHCT recipients was 52% and 85% respectively with a corresponding transplant-related mortality (TRM) of 11%. At 21 mo post-randomization, ixazomib vs. placebo groups had similar PFS (55.3% vs. 59.1%) and OS (95% vs. 87%, p = 0.17). Cumulative incidences of grade III-IV acute GVHD at 100 days (9.5% vs. 0%) or chronic GVHD at 12 months (69% vs 64%) were similar. Best response, incidence of progression for ixazomib vs. placebo groups were similar while cumulative incidence of transplant-related mortality (TRM) at 21 months was 0.0% and 4.5% (90%CI: 0.5-16.5%), respectively. Conclusions: AlloHCT with reduced intensity fludarabine/melphalan and a single pre-HCT dose of bortezomib is safe and can produce durable disease control in extremely high-risk patients. ixazomib maintenance after alloHCT could not be assessed as intended due to early termination of study, but there was no signal of an impact in outcomes. Clinical trial information: NCT02440464.

scholarly journals The oncogene BRAFV600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na+/I− targeting to the membrane

2006 ◽  
Vol 13 (1) ◽  
pp. 257-269 ◽  
Author(s):  
G Riesco-Eizaguirre ◽  
P Gutiérrez-Martínez ◽  
M A García-Cabezas ◽  
M Nistal ◽  
P Santisteban
Keyword(s):  
High Risk ◽  
Papillary Thyroid Carcinoma ◽  
Thyroid Carcinoma ◽  
Prognostic Impact ◽  
Erk Pathway ◽  
Papillary Thyroid ◽  
Thyroid Cells ◽  
Genetic Event ◽  
Total Body

The oncogene BRAFV600E is the most frequent genetic event in papillary thyroid carcinoma (PTC) but its prognostic impact still remains to be elucidated. We evaluated a representative series of 67 individuals with PTC who underwent total thyroidectomy. BRAF-positive tumours correlated with early recurrences (32% vs 7.6%; P=0.02) during a median postoperative follow-up period of 3 years. Interestingly, within the recurrences, a significant majority had negative radioiodine (131I) total body scans, predicting a poorer outcome as treatment with 131I is not effective. This last observation led us to investigate the role of BRAFV600E and the MEK-ERK pathway in thyroid dedifferentiation, particularly in Na+/I− symporter (NIS) impairment, as this thyroid-specific plasma membrane glycoprotein mediates active transport of I− into the thyroid follicular cells. A subset of 60 PTC samples was evaluated for NIS immunoreactivity and, accordingly, we confirmed a significant low NIS expression and impaired targeting to membranes in BRAF-positive samples (3.5% vs 30%; P=0.005). Furthermore, experiments with differentiated PCCl3 thyroid cells demonstrated that transient expression of BRAFV600E sharply impaired both NIS expression and targeting to membrane and, surprisingly, this impairment was not totally dependent on the MEK-ERK pathway. We have concluded that BRAFV600E is a new prognostic factor in PTC that correlates with a high risk of recurrences and less differentiated tumours due to the loss of NIS-mediated 131I uptake.

scholarly journals No difference in outcome between children and adolescents transplanted for acute lymphoblastic leukemia in second remission

Blood ◽  
2011 ◽  
Vol 118 (25) ◽  
pp. 6683-6690 ◽  
Author(s):  
Giorgio Dini ◽  
Marco Zecca ◽  
Adriana Balduzzi ◽  
Chiara Messina ◽  
Riccardo Masetti ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Complete Remission ◽  
Confidence Interval ◽  
Children And Adolescents ◽  
Lymphoblastic Leukemia ◽  
Disease Recurrence ◽  
Hematopoietic Stem ◽  
Free Survival ◽  
Total Body ◽  
Related Mortality

Abstract Acute lymphoblastic leukemia (ALL) in second complete remission is one of the most common indications for allogeneic hematopoietic stem cell transplantation (HSCT) in pediatric patients. We compared the outcome after HCST of adolescents, aged 14 to 18 years, with that of children (ie, patients < 14 years of age). Enrolled in the study were 395 patients given the allograft between January 1990 and December 2007; both children (334) and adolescents (61) were transplanted in the same pediatric institutions. All patients received a myeloablative regimen that included total body irradiation in the majority of them. The donor was an HLA-identical sibling for 199 patients and an unrelated volunteer in the remaining 196 patients. Children and adolescents had a comparable cumulative incidence of transplantation-related mortality, disease recurrence, and of both acute and chronic graft-versus-host disease. The 10-year probability of overall survival and event-free survival for the whole cohort of patients were 57% (95% confidence interval, 52%-62%) and 54% (95% confidence interval, 49%-59%), respectively, with no difference between children and adolescents. This study documents that adolescents with ALL in second complete remission given HSCT in pediatric centers have an outcome that does not differ from that of patients younger than 14 years of age.

scholarly journals A randomized trial comparing busulfan with total body irradiation as conditioning in allogeneic marrow transplant recipients with leukemia: a report from the Nordic Bone Marrow Transplantation Group

Blood ◽  
1994 ◽  
Vol 83 (9) ◽  
pp. 2723-2730 ◽  
Author(s):  
O Ringden ◽  
T Ruutu ◽  
M Remberger ◽  
J Nikoskelainen ◽  
L Volin ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Total Body Irradiation ◽  
Myeloid Leukemia ◽  
Advanced Disease ◽  
Treated Group ◽  
Early Disease ◽  
Free Survival ◽  
Grade Ii ◽  
Total Body ◽  
Related Mortality

Abstract Between October 1988 and December 1992, 167 patients with leukemia receiving marrow transplants from HLA-identical donors and conditioned with cyclophosphamide (120 mg/kg) were randomized to additional treatment with either busulfan (16 mg/kg, n = 88) or total body irradiation (TBI; n = 79). The busulfan-treated patients had an increased cumulative incidence of veno-occlusive disease of the liver, ie, 12% compared with 1% in the TBI group (P = .009). Furthermore, hemorrhagic cystitis occurred in 24% of the busulfan patients versus 8% in the TBI patients (P = .003). In patients with advanced disease beyond first remission or first chronic phase, transplantation-related mortality was 62% among the busulfan-treated patients compared with 12% among the TBI recipients (P = .002). These differences between the two groups were statistically significant in multivariate analysis. Seizures were seen in 6% of the busulfan-treated patients and were absent in the TBI group (P = .03). Grade II-IV of acute graft-versus- host disease (GVHD) was similar in the two groups, but grade III-IV and chronic disease was more common in the busulfan-treated group (P = .04). Death associated with GVHD occurred in 17% of the busulfan- treated group and 2% of the TBI group (P = .003). Patients treated with busulfan had a 3-year actuarial survival of 62%, which was worse than the 76% among those treated with TBI (P < .03). In multivariate analysis, poor survival was associated with advanced disease (P < .0001), no posttransplant septicemia (P = .0006), grade II-IV GVHD (P = .006), and busulfan treatment (P < .02). The incidence of relapse did not differ between the two groups. Relapse-free survival was also similar in the two treatment groups on analysis of data from all patients, children, patients with early disease, and those with acute myeloid leukemia, acute lymphoblastic leukemia, and chronic myeloid leukemia. However, in adults (P = .05) and patients with advanced disease (P = .005), leukemia-free survival was significantly better in those treated with TBI. We conclude that patients treated with busulfan have more early toxicity and an increased transplant-related mortality in patients with advanced disease. TBI is therefore the treatment of choice, especially in adults and patients with advanced disease. However, busulfan is an acceptable alternative for patients with early disease and for those in whom TBI is not feasible.

scholarly journals Where does transplant fit in the age of targeted therapies?

Hematology ◽  
2019 ◽  
Vol 2019 (1) ◽  
pp. 287-293 ◽  
Author(s):  
Victor A. Chow ◽  
Ajay K. Gopal
Keyword(s):  
Follicular Lymphoma ◽  
Hematopoietic Cell Transplantation ◽  
Treatment Options ◽  
Progression Free Survival ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Low Toxicity ◽  
First Recurrence ◽  
Autologous Hct

Abstract The role of hematopoietic cell transplantation (HCT) for indolent lymphoma has evolved over the last 5 years with the availability of novel low-toxicity therapies and a better understanding of the prognosis of these entities. However, despite numerous treatment options for patients with follicular lymphoma, none are thought to be curative, and many require ongoing therapy with chronic toxicity. Historical trials indicate that autologous HCT as initial consolidation leads to improved progression-free survival, but not overall survival (OS) and, thus, is not typically recommended. However, autologous HCT for chemosensitive relapse can be carried out with ∼1% early mortality risk, affording disease control lasting a median of 3 to 5 years and the potential to improve OS. These results may compare favorably in efficacy, toxicity, and cost vs multiple sequential novel therapies with shorter durations of benefit. Recent data indicate that autologous HCT in follicular lymphoma patients with early initial progression will result in more than one third being alive and without relapse at 5 years, leading to improved OS when used within a year of the first recurrence. Unlike other available therapies, allogeneic HCT has the potential to cure up to one half of those transplanted with indolent B-cell non-Hodgkin lymphoma, although the risks need to be recognized and appropriate patient and donor selection is critical to ensure the best outcomes. HCT continues to remain a viable option in the current era of multiple targeted agents.

Results of Alemtuzumab-Based Reduced-Intensity Allogeneic Transplantation for Advanced Chronic Lymphocytic Leukemia: A BSBMT Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2899-2899
Author(s):  
Julio Delgado ◽  
Kirsty Thomson ◽  
Nigel Russell ◽  
Joanne Ewing ◽  
Wendy Stewart ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hematopoietic Cell Transplantation ◽  
Fungal Infections ◽  
Progression Free Survival ◽  
Allogeneic Transplantation ◽  
Lymphocytic Leukemia ◽  
Free Survival ◽  
Autologous Hct ◽  
Reduced Intensity ◽  
Related Mortality

Abstract We report 41 consecutive patients with advanced chronic lymphocytic leukemia (CLL) who underwent allogeneic hematopoietic cell transplantation (HCT) following fludarabine, melphalan and alemtuzumab reduced intensity conditioning. Donors were 24 HLA-matched siblings and 17 unrelated volunteers (4 of them mismatched). Median age at transplant was 54 (range 37–67) years, interval from diagnosis to HCT was 54 (10–164) months, and number of previous chemotherapy regimens was 3 (1–6). Eleven patients were refractory to fludarabine at the time of transplant and 3 others (8%) had it stopped due to immune cytopenias. Eleven patients had failed autologous HCT. At the time of transplant, 7 patients (17%) had chemo-refractory and 34 (83%) chemo-sensitive disease, but only 5 (12%) were in complete remission. All but 3 patients had initial hematological recovery, but 5 more patients had delayed graft failure that responded to subsequent stem-cell infusions. Median intervals to neutrophil (&gt; 0.5 × 109/l) and platelet (&gt; 20 × 109/l) recovery were 14 (range 9–30) and 11 (range 8–45) days, respectively. Eleven patients (27%) relapsed and received escalated donor lymphocyte infusions, but only 3 of them had a sustained response. Acute and chronic graft-versus-host disease (GVHD) was observed in 17 (41%) and 13 (33%) patients, respectively. With a median follow-up of 15 (range 0.2–62) months, 17 patients have died, 5 of progressive disease and 12 of transplant-related complications. The 2-year overall survival, progression-free survival and transplant-related mortality are 51% (CI 33%–69%), 45% (27%–62%) and 26% (14%–46%), respectively (Figure 1). In multivariate analysis, fludarabine refractoriness prior to transplant was the only factor to predict a worse progression-free survival in this setting. In conclusion, the alemtuzumab-based regimen was feasible and effective in patients with CLL with a relatively low rate of GVHD. However, transplant-related mortality remains relatively high as a result of a variety of viral and fungal infections. Ongoing studies are aiming to address the efficacy of reduced doses of alemtuzumab in this group of very immunosupressed patients. Figure Figure

Tandem Versus Single Autologous Hematopoietic Cell Transplantation for Treatment of Multiple Myeloma: A Meta-Analysis of Randomized Controlled Trials (RCT).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 936-936
Author(s):  
Ambuj Kumar ◽  
Mohamed A. Kharfan-Dabaja ◽  
Axel Glasmacher ◽  
Benjamin Djulbegovic
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Hematopoietic Cell Transplantation ◽  
Response Rates ◽  
Event Free Survival ◽  
Free Survival ◽  
Randomized Controlled ◽  
Outcome Event ◽  
Treatment Related Mortality ◽  
Related Mortality

Abstract Background: Single autologous hematopoietic cell transplantation (AHCT) is considered standard therapy for patients with multiple myeloma (MM). Several observational studies and some RCTs have shown superior outcomes with tandem transplants; others have shown conflicting results. The objective of this study is to present the totality of evidence by conducting a systematic review to assess the efficacy of double ASCT in previously untreated MM patients. Methods: A systematic and comprehensive search of the literature was performed using MEDLINE, and Cochrane library databases from 1966–2007 for all phase III randomized controlled trials (RCT) comparing single versus tandem AHCT in previously untreated MM patients with previously. Additionally, we searched ASCO, ASH and European Society for hematology meeting abstracts between 2003–2007 years. Data was extracted and pooled on benefits and harms as per the methods recommended by the Cochrane Collaboration. Results: Altogether 5 RCTs enrolling 1569 patients met the inclusion criteria. Data were available from all trials for overall survival, and for the remaining outcomes data were extractable from 3 RCTs. As shown in figure 1a. overall survival was not significantly different between tandem and single transplant (hazard ratio [HR]=0.91, 95% CI 0.81 to 1.02, p=0.09). However, there was a significant improvement in event free survival (HR=0.74, 95%CI 0.64, 0.85; p=0.00002, see figure 1b.) and response rates (HR=0.72, 95%CI 0.52 to 0.99; p=0.04, see figure 2a.) favoring tandem AHCT, but at the expense of significant increase in treatment related mortality (HR=1.79, 95%CI 1.03 to 3.11; p=0.04, see figure 2b.). There was no statistically significant heterogeneity between trials (see figure 1 and 2). Conclusion: The available existing evidence shows that, in patients with previously untreated MM, tandem AHCT does not result in improved survival. Tandem AHCT is associated with improved event-free survival and response rates but at the cost of significant increase in fatal side effects (see figure). However, the latter conclusion can also be attributed to “outcome reporting bias” since data for non-survival outcomes were only available in 3 out of 5 RCTs. Figure 1a. Double versus Single transplant in Multiple Myeloma Outcome: Overall Survival Figure 1b. Double versus Single transplant in Multiple Myeloma Outcome: Event-free survival Figure 1a. Double versus Single transplant in Multiple Myeloma Outcome: Overall Survival . / Figure 1b. . / Double versus Single transplant in Multiple Myeloma Outcome: Event-free survival Figure 2a. Double versus Single transplant in Multiple Myeloma Outcome: Response rates Figure 2b. Double versus Single transplant in Multiple Myeloma Outcome: Treatment related mortality Figure 2a. Double versus Single transplant in Multiple Myeloma Outcome: Response rates . / Figure 2b. . / Double versus Single transplant in Multiple Myeloma Outcome: Treatment related mortality

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