Palifermin Does Not Influence the Incidence and Severity of GvHD Nor Long-Term Survival of Patients with Hematological Diseases Undergoing HSCT

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4301-4301
Author(s):  
Barbara Nasilowska-Adamska ◽  
Agnieszka Tomaszewska ◽  
Richard M. Szydlo ◽  
Piotr Rzepecki ◽  
Anna Czyz ◽  
...  
Keyword(s):  
Group Versus ◽  
Rank Test ◽  
Control Group ◽  
High Dose ◽  
Secondary Malignancies ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Hematological Diseases

Abstract AIMS: Oral mucositis (OM) is a frequent complication of myeloablative therapy and hematopoietic stem cell transplantation (HSCT). Palifermin was found to reduce the incidence, duration and severity of OM induced by high-dose chemotherapy with HSCT (Bone Marrow Transplant.2007;40:983–8). However, additional data on the long-term safety of palifermin and its potential influence on graft versus host disease (GvHD) were missing. In this multi-center, non-randomized, matched-control study we assessed overall survival (OS), incidence and severity of acute/chronicGvHD (a/cGvHD) and incidence of secondary malignancies in patients with hematological diseases treated with HSCT who received palifermin as a prophylaxis for OM. METHODS AND RESULTS: One hundred and twenty patients with hematological diseases transplanted between December 2001 and December 2007 were enrolled to this study. Sixty patients (50%) received palifermin (60μg/kg/day) for three consecutive days before and after conditioning therapy (palifermin group). Median age of patients was 37.5 years (range, 19 to 63) in the palifermin group and 35.5 years (range, 18 to 64) in the control group. There were no statistical differences between studied groups in terms of other clinical characteristics, including gender, diagnosis, type of transplant, conditioning regimens or GvHD prophylaxis. Kaplan-Meier curves for OS were calculated and compared using the log-rank test. Fisher’s exact and the χ2 trend tests were applied for the analysis of the GvHD data. Twenty one (35%) autologous and thirty nine (65%) allogeneic HSCT (HLA-matched related and unrelated) were performed in each group. Following allogeneic HSCT, the incidence of aGvHD grade 1–4 was 28.2% and 38.4% (p=0.34) and cGvHD was 41% and 53.8% (p=0.70) in the palifermin and control groups, respectively. The incidence of aGvHD severity grade 0,I,II,III,IV was 69.2%, 5.1%, 17.9%, 2.5%, 2.5% in the palifermin and 61.5%, 12.8%, 12.8%, 10.2%, 5.2% in the control group, respectively (p>0.4 for each). The incidence of limited and extensive cGvHD was 17.9% and 23% in the palifermin group versus 25.6% and 28.2% in the control group (p=0.32 and p=0.50, respectively). The estimated 2-years OS (72.8% and 79.8%, respectively) also didn’t differ significantly between studied groups (p=0.13). We didn’t observe any secondary malignancies in patients enrolled into the study. CONCLUSIONS: Administration of palifermin doesn’t seem to influence the incidence and severity of a/cGvHD, secondary malignancies occurrence and OS in patients with hematological diseases undergoing HSCT.

scholarly journals Improved Long-Term Survival with Edaravone Therapy in Patients with Amyotrophic Lateral Sclerosis: A Retrospective Single-Center Study in Japan

2021 ◽  
Vol 14 (8) ◽  
pp. 705
Author(s):  
Hideki Houzen ◽  
Takahiro Kano ◽  
Kazuhiro Horiuchi ◽  
Masahiro Wakita ◽  
Azusa Nagai ◽  
...  
Keyword(s):  
Amyotrophic Lateral Sclerosis ◽  
Rank Test ◽  
Positive Pressure ◽  
Control Group ◽  
Single Center ◽  
Term Survival ◽  
Long Term Survival ◽  
Kaplan Meier ◽  
Lateral Sclerosis

Reports on the long-term survival effect of edaravone, which was approved for the treatment of amyotrophic lateral sclerosis (ALS) in 2015 in Japan, are rare. Herein, we report our retrospective analysis of 45 consecutive patients with ALS who initially visited our hospital between 2013 and 2018. Of these, 22 patients were treated with edaravone for an average duration of 26.6 (range, 2–64) months, whereas the remaining patients were not treated with edaravone and comprised the control group. There were no differences in baseline demographics between the two groups. The primary endpoint was tracheostomy positive-pressure ventilation (TPPV) or death, and the follow-up period ended in December 2020. The survival rate was significantly better in the edaravone group than in the control group based on the Kaplan–Meier analysis, which revealed that the median survival durations were 49 (9–88) and 25 (8–41) months in the edaravone and control groups, respectively (p = 0.001, log-rank test). There were no serious edaravone-associated adverse effects during the study period. Overall, the findings of this single-center retrospective study suggest that edaravone might prolong survival in patients with ALS.

Long-Term Survival Is Comparable between Palifermin-Treated and Placebo-Treated Patients (Pts) with Hematologic Malignancies (HM) Undergoing High-Dose Chemotherapy and Total Body Irradiation Followed by Autologous Hematopoietic Stem Cell Transplantation (HSCT).

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2925-2925 ◽  
Author(s):  
Ricardo Spielberger ◽  
Christos Emmanouilides ◽  
William Bensinger ◽  
Alan Rong ◽  
Alessandra Cesano ◽  
...  
Keyword(s):  
Controlled Study ◽  
Secondary Malignancies ◽  
Double Blind ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Double Blind Placebo ◽  
Disease Outcomes ◽  
Long Term Follow Up

Abstract Oral mucositis (OM) is a severely debilitating side effect of chemoradiotherapy that often causes significant pain, diminished quality of life, and increased risk of infections. Palifermin decreases the incidence and duration of severe OM in HM pts receiving myelotoxic therapy and HSCT. Palifermin safety and efficacy have not been established in the non-HM setting. Since the rHuKGF receptor is not expressed by HM, palifermin is not expected to interfere with long-term disease outcomes in this pt population. Aim: We assessed palifermin’s effects on the long-term disease outcomes (survival, disease progression, secondary malignancies) in pts with HM. Methods: Long-term follow-up data were pooled from a 1998 phase 2, double-blind, placebo-controlled study (n=86) and a 2000 double-blind, placebo-controlled phase 3 study (n=212). The analysis included 152 pts treated with palifermin and 146 pts treated with placebo. Pts were assessed at 6-month intervals during the first year and annually thereafter until death or loss to follow-up. The Kaplan-Meier (K–M) method provided estimates of the safety endpoints. Data reported here are as of August 2004. Results: There were 298 pts (152 palifermin: 146 placebo) monitored for long-term follow-up. The median follow-up period was 23.3 months for palifermin and 23.5 months for placebo. The overall survival and progression-free survival curves (p=0.474 and p=0.253, respectively) are similar between the palifermin and placebo groups. Secondary malignancies occurred in only 6 of 152 (3%) palifermin and 5 of 146 (4%) placebo pts. All secondary malignancies were myelodysplastic syndromes: 9 patients with diagnoses of Non-Hodgkin’s lymphoma and 2 patients of Hodgkin’s Disease. The number of deaths was similar between the groups (30% palifermin; 27% placebo); most deaths occurred within 12 months of randomization and were attributable to the underlying HM disease. Conclusion: Use of palifermin for the prevention of severe OM has shown no negative impact on long-term disease outcomes, including survival, in the HSCT setting for patients with HM.

scholarly journals Allogeneic Stem Cell Transplantation in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 55
Author(s):  
Christine Greil ◽  
Monika Engelhardt ◽  
Jürgen Finke ◽  
Ralph Wäsch
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Risk Groups ◽  
High Dose ◽  
Term Survival ◽  
Hematopoietic Stem

The development of new inhibitory and immunological agents and combination therapies significantly improved response rates and survival of patients diagnosed with multiple myeloma (MM) in the last decade, but the disease is still considered to be incurable by current standards and the prognosis is dismal especially in high-risk groups and in relapsed and/or refractory patients. Allogeneic hematopoietic stem cell transplantation (allo-SCT) may enable long-term survival and even cure for individual patients via an immune-mediated graft-versus-myeloma (GvM) effect, but remains controversial due to relevant transplant-related risks, particularly immunosuppression and graft-versus-host disease, and a substantial non-relapse mortality. The decreased risk of disease progression may outweigh this treatment-related toxicity for young, fit patients in high-risk constellations with otherwise often poor long-term prognosis. Here, allo-SCT should be considered within clinical trials in first-line as part of a tandem approach to separate myeloablation achieved by high-dose chemotherapy with autologous SCT, and following allo-SCT with a reduced-intensity conditioning to minimize treatment-related organ toxicities but allow GvM effect. Our review aims to better define the role of allo-SCT in myeloma treatment particularly in the context of new immunomodulatory approaches.

Increased Risk for EBV-Lymphoma after Allogeneic Hsct in Adult Lymphoma Patients?A Retrospective Study of Reduced Compared to Myeloablative Conditioning.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5116-5116
Author(s):  
Hans G. Hagglund ◽  
Mats Brune ◽  
Gunnar Oberg ◽  
Hans Hagberg ◽  
Niklas Theorin ◽  
...  
Keyword(s):  
Patient Survival ◽  
Group Versus ◽  
Myeloablative Conditioning ◽  
Term Survival ◽  
Allogeneic Hsct ◽  
Increased Risk ◽  
Unrelated Donors ◽  
Causes Of Deaths

Abstract The aim of this study was to compare the outcome of allogeneic HSCT after myeloablative versus reduced intensity conditioning (RIC) for lymphoma. From January 1984 to June 2004, 87 patients underwent HSCT for lymphoma (including 41 patients with RIC, all grafted after May 1998). The diagnoses were 15 and 24 aggressive, 18 and 17 indolent and 8 and 5 HD lymphomas, in the RIC and myeloablative groups, respectively. There were 64 males and 23 females. The median age was 40 (16–61). The donors were 3 identical twins, 55 related and 29 unrelated donors. The conditioning was based on chemotherapy only in 32 and 8 and irradiation in combination with chemotherapy in 9 and 38 patients (p<0.001), in the RIC and myeloablative groups, respectively. Immunosuppression consisted of MTX and CsA in 68, CsA and MMF in 10, MTX or CsA in 4, T-cell depletion in 2 and 3 patients had no prophylaxis. In the RIC group the median age was significantly higher 49 (25–61) years than in the myeloablative group 38 (16–53) years (p<0.001). PBSC was used in 36 (88%) patients in the RIC group versus 17 (37%) (p<.001) in the myeloablative group. The causes of deaths were 11 infections, 10 relapses, 6 EBV-lymphomas, 6 related to toxicity and 3 to GVHD and 1 renal cancer. Conclusions: Long term survival was seen in more than 50 % of patients with relapsing lymphoma after allogeneic HSCT. EBV lymphoma was the cause of death in 7% of the patients. The patient survival, TRM and relapse outcomes were similar after RIC and myeloablative conditioning but each subgroup is small. In the RIC group the patients were older, grafted in more advanced disease and the follow up shorter compared to the myeloablative group, therefore the results must be interpreted with care. Results RIC Myeloablative p GVHD (absolute incidence) Acute II-IV 43% 16% ns Chronic 32% 57% 0.06 Outcome (2-years probability) TRM 25% 39% ns Relapse 21% 16% ns Patient survival 61% 54% ns

Marked Improvement in Short- and Long-Term Survival in Severe Aplastic Anemia Patients Treated with Immunosuppression in the Past 18 Years.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1698-1698
Author(s):  
Phillip Scheinberg ◽  
Colin O. Wu ◽  
Olga Nunez ◽  
Neal S. Young
Keyword(s):  
Supportive Care ◽  
Aplastic Anemia ◽  
Response Rate ◽  
Severe Aplastic Anemia ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Long Term Survival ◽  
Allogeneic Hsct ◽  
Short And Long Term

Abstract Forty years ago severe aplastic anemia (SAA) was almost universally fatal disease, but now most patients can be successfully treated with hematopoietic stem cell transplantation (HSCT) or immunosuppressive therapy (IST). Since the majority of patients are not suitable candidates for allogeneic HSCT from a histocompatible sibling, IST is usually the treatment of choice. From the introduction of the standard anti-thymocyte globulin (ATG) + cyclosporine (CsA) regimen in the 1980s, the hematologic response rate has been 60–70% despite efforts to improve on the ATG+CsA platform. Across many protocols, there is a strong link between response to IST and survival. We examined short and long term survival of patients who were treated with initial IST at the Clinical Center of the National Institutes of Health from 1989 to 2006; a total of 372 patients were analyzed in 3 separate cohorts: those who received IST from 1989–1995; 1996–2001 and 2002–2006. Thirty-two deaths occurred within the 6-months period of IST with 15 being attributed to a fungal infection. The distribution of early deaths (< 6 months) in relation to the different time periods were 15% (1989–1995); 9% (1996–2001); and 5% (2002–2006) (p = 0.003). Survival beyond 6 months also improved (1989–1995 and 2002–2006, 65% vs. 85%, respectively; p < 0.01). Surprisingly, the survival benefit was most striking among patients who did not respond to IST at 6 months. Among the total 116 non-responders, the number of patients who received a second course of IST was 0% (1989–1995), 37% (1996–2001) and 51% (2002–2006); those who underwent HSCT were 19% (1989–1995), 23% (1996–2001) and 18% (2002–2006); and those who did not receive a second course of IST or HSCT were 83% (1989–1995), 29% (1996–2001) and 11% (2002–2006). We draw two major conclusions from our data analysis. First, improvement in short term survival over the last two decades is most likely due to advances in supportive care, as the response rate to horse ATG + CsA has remained largely unchanged during the same time period. The marked decline in deaths due to invasive Aspergillosis infection suggests that the introduction of effective and relatively nontoxic antifungal drugs is of prime importance (e.g., voriconazole in 2002 and caspofungin in 2004). Second, the utilization of secondary therapies--a repeat course of IST and allogeneic HSCT for older adults and matched unrelated transplants for younger individuals--have salvaged patients who are primary ATG-failures. The advances in supportive care also impact long term survival in those who receive salvage therapies and in those who fail repeated courses of IST and are not suitable candidates for HSCT, who now can be adequately maintained on growth factor and transfusion support, often for years. Current survival rates in SAA should be weighed when in considering treatment algorithms for patients who fail initial IST.

scholarly journals Allogeneic stem cell transplantation mitigates the adverse prognostic impact of high diagnostic BAALC and MN1 expression in AML

2020 ◽  
Vol 99 (10) ◽  
pp. 2417-2427
Author(s):  
Madlen Jentzsch ◽  
Marius Bill ◽  
Juliane Grimm ◽  
Dominic Brauer ◽  
Donata Backhaus ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Prognostic Impact ◽  
Term Survival ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Copy Numbers ◽  
Droplet Pcr

Abstract For most acute myeloid leukemia (AML) patients, an allogeneic hematopoietic stem cell transplantation (HSCT) offers the highest chance of sustained remissions and long-term survival. At diagnosis, high expression of the AML-associated genes BAALC (brain and acute leukemia, cytoplasmic) and MN1 (meningioma-1) were repeatedly linked to inferior outcomes in patients consolidated with chemotherapy while data for patients receiving HSCT remain limited. Using clinically applicable digital droplet PCR assays, we analyzed the diagnostic BAALC/ABL1 and MN1/ABL1 copy numbers in 302 AML patients. High BAALC/ABL1 and MN1/ABL1 copy numbers associated with common adverse prognostic factors at diagnosis. However, while high diagnostic copy numbers of both genes associated with shorter event free survival (EFS) and overall survival (OS) in patients receiving chemotherapy, there was no prognostic impact in patients undergoing HSCT. Our data suggests that the adverse prognostic impact of high BAALC and MN1 expression are mitigated by allogeneic HSCT. But preHSCT BAALC/ABL1 and MN1/ABL1 assessed in remission prior to HSCT remained prognosticators for EFS and OS independent of the diagnostic expression status. Whether allogeneic HSCT may improve survival for AML patients with high diagnostic BAALC or MN1 expression should be investigated prospectively and may improve informed decisions towards individualized consolidation options in AML.

Sequential Versus Single High-Dose Chemotherapy in Patients With Relapsed or Refractory Germ Cell Tumors: Long-Term Results of a Prospective Randomized Trial

2012 ◽  
Vol 30 (8) ◽  
pp. 800-805 ◽  
Author(s):  
Anja Lorch ◽  
Antje Kleinhans ◽  
Andrew Kramar ◽  
Christian K. Kollmannsberger ◽  
Jörg T. Hartmann ◽  
...  
Keyword(s):  
Germ Cell ◽  
Survival Rates ◽  
Germ Cell Tumors ◽  
High Dose Chemotherapy ◽  
Long Term Results ◽  
Rank Test ◽  
High Dose ◽  
Term Survival ◽  
Long Term Survival

Purpose To evaluate the long-term survival rates in patients with relapsed or refractory germ cell tumors (GCTs) after single or sequential high-dose chemotherapy (HDCT). Patients and Methods Between November 1999 and November 2004, 211 patients with relapsed or refractory GCT were randomly assigned to treatment with either one cycle of cisplatin 100 mg/m2, etoposide 375 mg/m2, and ifosfamide 6 g/m2 (VIP) plus three cycles of high-dose carboplatin 1,500 mg/m2 and etoposide 1,500 mg/m2 (CE, arm A) or three cycles of VIP plus one cycle of high-dose carboplatin 2,200 mg/m2, etoposide 1,800 mg/m2, and cyclophosphamide 6,400 mg/m2 (CEC, arm B) followed by autologous stem-cell reinfusion. Long-term progression-free survival (PFS) and overall survival (OS) 6 years after random assignment of the last patient were compared by using the log-rank test. Results Overall, 108 and 103 patients were randomly assigned to arms A and B, respectivelyl. The study was stopped prematurely because of excess treatment-related mortality in arm B (14%) compared with that in arm A (4%; P = .01). As of December 2010, nine (5%) of 211 patients were lost to follow-up; 94 (45%) of 211 are alive and 88 (94%) of 94 patients are progression free. Five-year PFS is 47% (95% CI, 37% to 56%) in arm A and 45% (95% CI, 35% to 55%) in arm B (hazard ratio [HR], 1.16; 95% CI, 0.79 to 1.70; P = .454). Five-year OS is 49% (95% CI, 40% to 59%) in arm A and 39% (95% CI, 30% to 49%) in arm B (HR, 1.42; 95% CI, 0.99 to 2.05; P = .057). Conclusion Patients with relapsed or refractory GCT achieve durable long-term survival after single as well as sequential HDCT. Fewer early deaths related to toxicity translated into superior long-term OS after sequential HDCT.

Non-Myeloablative vs. Conventional Allogeneic Hematopoietic Stem Cell Transplantation for Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1132-1132
Author(s):  
Brad Pohlman ◽  
Tao Jin ◽  
Elizabeth Kuczkowski ◽  
Stacey Brown ◽  
Ronald Sobecks ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Hodgkin Lymphoma ◽  
Cell Transplantation ◽  
High Dose ◽  
Cell Transplant ◽  
Term Survival ◽  
Hematopoietic Stem

Abstract Non-myeloablative allogeneic stem cell transplantation (NMT) is increasingly used as an alternative to conventional bone marrow transplantation (BMT). Limited NMT data is available for lymphoma patients (pts). Most series include all hematological malignancies and only a minority with Hodgkin lymphoma (HL) or non-Hodgkin lymphoma (NHL). Therefore, we reviewed the Cleveland Clinic BMT Program experience with lymphoma pts and specifically compared the outcome between NMT and BMT. Between July 2, 1985 and December 7, 2004, 67 pts received a matched related (n=47) or unrelated (n=20) donor BMT (n=46) or NMT (n=21) for HL (n=11), aggressive NHL (n=32), indolent NHL (n=23), or unknown NHL (n=1). Pts with lymphoblastic, Burkitt, or atypical Burkitt-like lymphoma were excluded. Compared to BMT pts, NMT pts were older, had longer time from diagnosis to transplant (tx), and were more likely to have a normal LDH and be in remission (CR/PR) at tx. The median follow-up of surviving BMT and NMT pts was 73.8 (range 11.8–106.7) and 20.6 (range 2.8–44.0) months, respectively. 18 (39%) BMT and 5 (24%) NMT pts progressed, and 9 (20%) BMT and 2 (10%) NMT pts died from lymphoma. The incidence of grade 2–4 acute GVHD was not different between the BMT and NMT groups. Among all pts, the risk of lymphoma progression was significantly higher in pts with compared to pts without GVHD (Figure 1). The overall survival for NMT pts was significantly better than for BMT pts (P=.019). Among 15 pts that previously received high dose therapy with autologous stem cell transplant (ASCT), all 7 BMT pts died a median of 1 (range 1–14) month post-BMT while 4/8 NMT pts remained alive 8, 21, 29, and 33 months post-NMT. By multivariate analysis, BMT (HR 7.74, 95% CI 2.49–24.0, P<.001), HL (HR 6.52, 95% CI 2.04-20-85, P=.002), prior ASCT (HR 3.33, 95% CI 1.20–9.25, P=.021), and increasing age by decade (HR 1.7, 95% CI 1.11–2.62, P=0.14) were associated with a significantly higher mortality while CR/PR at tx was associated with a significantly lower mortality (HR 0.44, 95% CI 0.21–0.93, P=.032). Restricting the multivariate analysis to the 56 NHL pts identified no significant independent prognostic factors. Finally, excluding the 15 pts with prior ASCT showed that BMT, >3 prior chemotherapy regimens, tumor >10 cm at diagnosis, older age, and no remission at tx were all associated with a significantly higher mortality. We conclude that: 1) lymphoma progression and lymphoma- or transplant-related death beyond 2 years are uncommon; 2) BMT after failed ASCT is uniformly fatal while NMT (even after failed ASCT) may lead to long-term survival; 3) GVHD (with its presumed graft vs. lymhoma effect) is important for long-term, progression-free survival; 4) compared to BMT, NMT is associated with a better OS (although pt selection may account for some of the observed difference), and 5) both NMT and BMT are appropriate options for selected NHL pts. Whether NMT or BMT offers any benefit compared to ASCT for HL pts is unclear. Figure Figure

Hematopoietic Stem Cell Transplantation (HSCT) in Waldenström Macroglobulinemia (Wm), Update of the French Experience in 54 Cases.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3015-3015 ◽  
Author(s):  
N. Dhedin ◽  
R. Tabrizi ◽  
P.E. Bulabois ◽  
S. Le Gouill ◽  
V. Coiteux ◽  
...  
Keyword(s):  
Disease Control ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Heavily Pretreated ◽  
Autologous Hsct ◽  
Grade Iii

Abstract Introduction: HSCT has been developed in few Wm cases and is nowadays challenged by other innovative approaches. However, high dose therapy followed by autologous HSCT (HD-auto) produces high response rate and some long term responses while allogeneic HSCT performed after either myeloablative (MA-allo) or reduced intensity conditioning (RIC-allo) regimens may be cure of Wm (Dreger 1998, Tournilhac 2003, Maloney 2006). Methods: We updated and extended our retrospective experience on 32 HD-auto, 11 MA-allo and 11-RIC-allo performed from 1990 to 2006 in 51 patients from 18 institutions. A MA-allo and a RIC-allo were performed in 1 and 2 cases respectively following relapse after a 1st HD-auto. Results: Data are presented in the table. HD-auto MA-allo RIC-allo Nb 32 11 11 Median age at transplant 56 46 56 Interval: diagnosis-transplant 38 50 74 Chemoresistance at transplant 25% 36% 55% Conditioning regimen BEAM (13), TBI/melphalan (9), TBI/endoxan (7), other (3) TBI/endoxan (9), other (2) TBI/fluda (10), other (1) Donor Sibling (9), unrelated (2) Sibling (8), unrelated (2), cord blood (1) Median follow up (m) 45 (3–121) 68 (3–132) 22(2–60) Relapse 18 (56%) 4 (36%) 0 Transplant related mortality 12,5% (one 2th cancer) 36% 27% (one 2th cancer) overall survival (1;3;5y) 87%, 77%, 58% 64%, 54%, 54% 82%, 68%, 68% Event free survival (5y) 25% 48% 68% Acute GVHD developed following 9 MA-allo [Grade III-IV (n=1)] and 8 RIC-allo [Grade III-IV (n=1)]. Chronic GVHD developed following 7 MA-allo [limited (n=5), extensive (n=2)] and 5 RIC-allo [limited (n=2), extensive (n=3)]. Conclusion: We confirm that autologous HSCT achieves some long term responses even in heavily pretreated patients. Allogeneic HSCT induces very long term disease control and may cure WM. Specially, the RIC-allo gives impressive results on disease control in a set of older patients, with refractory disease, mostly heavily pretreated.

Allogeneic Hematopoietic Stem Cell Transplant (HSCT) Versus Conventional Chemotherapy in Patients with Acute Myelogenous Leukemia (AML) and High-Risk Myelodysplastic Syndrome (MDS) Attaining Complete Remission (CR1) Post Induction Chemotherapy: a Retrospective Case Control Study.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1125-1125
Author(s):  
Yvonne A Efebera ◽  
Hagop M. Kantarjian ◽  
Borje Andersson ◽  
Sherry Pierce ◽  
Leandro De Padua Silva ◽  
...  
Keyword(s):  
Stem Cell ◽  
High Risk ◽  
Myelogenous Leukemia ◽  
Control Group ◽  
High Dose ◽  
Cell Transplant ◽  
Hematopoietic Stem ◽  
Allogeneic Hsct ◽  
Chemotherapy Group

Abstract The role of allogeneic HSCT in patients with AML/MDS in CR1 is not well established. Historically, high rates of non-relapse mortality (NRM) associated with HSCT have negatively counterbalanced the reduced relapse rate associated with the graft-versus leukemia effect. We hypothesized that if NRM is reduced, allogeneic HSCT will improve relapse-free survival (RFS) when compared to chemotherapy alone. Here we compared outcomes of patients treated with busulfan 130 mg/m2 and fludarabine 40 mg/m2 for 4 days (our ablative regimen with the lowest NRM rate) and matched controls treated without HSCT. Methods: Between January, 2001 and December, 2004, 36 patients with AML (n=28) or high-risk MDS (n=8) in CR1 were transplanted. Year 2004 was chosen as the cutoff to allow for significant follow up time. Controls were 110 patients treated in the leukemia department without HSCT between 1980 and 2004, selected to match according to age, cytogenetics, and time in CR1 (in order to compensate for the time in CR1 that preceded HSCT, which was a median of 3.3 months, range 0.36–12.4 months). All patients received induction regimen containing high dose cytarabine. Eligible for HSCT were patients in remission that did not have good prognosis cytogenetics that had a performance status of 0 or 1, adequate organ function, no uncontrolled infection and age 18–65 years. Primary end point was RFS (measured from CR1 date to relapse or death). Results: Median age was 42 years in both groups (range 21–62). Proportion of patients with intermediate risk and high-risk cytogenetics in the transplant and chemo groups was as follows: 67% versus 72%, and 33% versus 28%, respectively. The median time from diagnosis to CR1 was 1.5 month (range, 0.6–17.2) and 1.15 month (range, 0.13–5) in the HSCT and chemotherapy groups respectively. Patients in the control group had de novo AML in 92% of the cases (n=102) versus 64% in the HSCT cohort (n=23), while more patients in the transplant group had secondary AML or MDS (36% vs 8%). Donors were HLA matched related in 22 cases (61%), and a matched unrelated donor in 12 patients (39%). Stem cell source was the peripheral blood (n=20; 56%) or bone marrow (n=16, 44%). Median follow-up of surviving patients is 5.2 years for the HSCT (range, 2.4–7) versus 9.1 years (3.9–21) for the chemotherapy group, respectively. Twelve HSCT patients have died (33%), versus 76 (69%) in the chemotherapy group. Relapse occurred in 12/36 patients (33%) in the HSCT group versus 79/110 (72%) in the control group. NRM in the HSCT cohort was zero at 100 days, 7% at one year and 15% at 3 years (1 patient died of chronic GVHD and 1 died of pneumonia). RFS is shown in the picture. RFS of transplant patients remains superior if we only used control patients treated in the same time frame in which the transplants were performed (ie, year 2001 to 2004; p=0.0003) Conclusion: These results indicate improved survival with HSCT and support the conduct of a randomized comparison of chemotherapy versus allogeneic HSCT using Busulfan Fludarabine preparative regimen for AML in CR1. Figure Figure

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