No Benefit of Adding High-Dose Melphalan (HDM) Suppported by Autologous Stem Cell Transplantation (SCT) over Treatment with Conventional Induction, HD ARAC Consolidation, and Auto SCT (Busulfan + HDM) for Acute Myelogenous Leukemia (AML) under 60: First Results of the Randomized AML 2001 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 608-608 ◽  
Author(s):  
B. Lioure ◽  
A. Pigneux ◽  
C. Recher ◽  
F. Witz ◽  
T. Lamy ◽  
...  
Keyword(s):  
Early Death ◽  
Myelogenous Leukemia ◽  
High Dose ◽  
Marrow Graft ◽  
Prognostic Features ◽  
Frequent Use ◽  
Significant Difference ◽  
First Results ◽  
High Dose Melphalan

Abstract From 11/2001 until 04/2005, 832 patients (median age 46, 18–60) with AML (previous diagnosis of myelodysplasia or myeloproliferative disorder, and M3 excluded) were 1st randomized to received induction with continuous IV ARAC (200 mg/m2, x 7d) and Daunorubicin (D: 60 mg/m2 x 3d) OR Idarubicin (I: 8 mg/m2 x 5d). If marrow blasts > 5% on D15, 2nd induction course was applied (D: 35 mg/m2 x 2d OR I: 8 mg/m2 x 2d plus ARAC 1 g/m2 x 4 doses over 2d). After achieving CR, all patients received low dose consolidation (D: 60 mg/m2 x 2d OR I: 12 mg/m2 x 2d plus SC ARAC 100 mg/m2 x 7d). Patients with HLA-identical sibling receive a T-replete alloSCT: either conventional (bone marrow graft, TBI-cyclophosphamide, ciclosporin-methotrexate) if age ≤ 50 = arm M; or non myeloablative (NST: peripheral blood, Busulfan (Bu)-Fludarabin-Thymoglobulin®, ciclosporin alone), AFTER intensive consolidation (idem below) if age 51–60 = arm m. A small subgroup of patients (3 % patients in CR) with a donor but low-risk prognostic features (favorable cytogenetics, no hyperleucocytosis, CR after 1 induction) did not receive 1st line alloSCT but intensive consolidation then a 2nd HD ARAC course; alloSCT was therefore considered for relapse = arm C. Other patients proceed to 2nd randomization: intensive consolidation (D: 60 mg/m2 x 2d OR I: 12 mg/m2 x 2d plus ARAC 3 g/m2 x 8 doses over 4d) PLUS 1 autoSCT (Bu 16 mg/kg over 4d + HDM 140 mg/m2) = arm A; or intensive consolidation PLUS 2 autoSCT (HDM 200 mg/m2 THEN Bu 16 mg/kg over 4d + HDM 140 mg/m2) = arm B. After 1st randomization (D vs I), no difference was observed between 2 arms regarding age, leukocytosis or cytogenetic subgroups: favorable (t8;21) or inv16: D = I 13%), intermediate (D 66%, I 59%), defavorable (5, 7, complex, 11q23 except t(9;11) or 3q; D 21%, I 28%). Use of both anthracyclins results in same CR rate (D 83% vs I 85%); early death (3%); projected EFS (D 46% vs I 50%, p = 0,28) and OS (D 61% vs I 64%) at 2 years. Noteworthy was the more frequent use of 2nd induction course to obtain CR with D (30%) as compared with I (22%). 78% of all patients in CR proceeded to 2nd randomization or were assigned to alloSCT arms (33 % of them). Actual results concern 550 patients with 15 months follow-up. No benefit was observed with addition of HDM 200 for 2y projected DFS (A 53% vs B 49%) or OS (A = B 68%). Toxic death rate was higher in arm B, accounting for 18% total deaths vs 6% in arm A. Conventional alloSCT results in better 2y DFS than combined arms A+B (M 71% vs A+B 52%, p=0,007) thought 2y OS advantage remains non significant (M 77% vs A+B 68%, p=0,06). No significant difference was observed between conventional and NST (2y DFS 62%, OS 68%). Advantage for NST over autoSCT arms was non significant for DFS (p=0,24) and OS. Same results are obtained if considering only patients aged > 50 : 2y EFS (m 62% vs A+B 50%, p=0,27) and OS (m 68% vs A+B 65%). In conclusion: conventional alloSCT remains the best consolidation treatment for patients ≤ 50 with AML in CR1; NST after intensive consolidation seems promising for older patients and may extend use of alternative sources of alloSCT; HDM course adds no benefit for these patients. Data with more than 2 years follow-up will be presented.

Allogeneic Stem Cell Transplantation (SCT) with Non Myeloablative Conditioning Regimen (NST) Following Intensive Consolidation May Be Equivalent to Conventional alloSCT and Superior to autoSCT for Patients over 50 with Acute Myeloid Leukemia (AML) in 1stCR: First Results of the AML 2001 Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 319-319 ◽  
Author(s):  
B. Lioure ◽  
J. Delaunay ◽  
D. Blaise ◽  
N. Milpied ◽  
P. Guardiola ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Phase Iii ◽  
Late Relapse ◽  
Marrow Graft ◽  
Hematopoietic Stem ◽  
Prognostic Features ◽  
Significant Difference ◽  
First Results ◽  
Alternative Sources

Abstract From 11/01 until 04/05, 832 patients (median age 46, 18–60) with AML (previous diagnosis of myelodysplasia or myeloproliferative disorder, and M3 excluded) were included in prospective phase III AML 2001 trial. After achieving CR, research to identify an HLA-identical sibling was performed for all patients as they received low dose consolidation (Daunorubicin (D): 60 mg/m2 × 2d OR Idarubicin (I): 12 mg/m2 × 2d plus SC ARAC 100 mg/m2 ×7d). 33 % patients had a donor then could proceed to a T-replete alloSCT: either conventional if age ≤ 50 (bone marrow graft; conditioning regimen: TBI (12 Gy 6 fractions over 3d) - cyclophosphamide (60 mg/kg × 2d); GvHD prophylaxis: ciclosporin-methotrexate d1+3+6) = arm M; or NST if age 51–60 (peripheral blood; Busulfan (oral Bu 4–8 mg/kg over 2d) - Fludarabin (30 mg/m2 × 4d) – Thymoglobulin® (2,5 mg/kg × 2d); ciclosporin alone), AFTER intensive consolidation (D: 60 mg/m2 × 2d OR I: 12 mg/m2 × 2d plus ARAC 3 g/m2 × 8 doses over 4d) = arm m. A small group of patients with a donor but low-risk prognostic features (favorable cytogenetics, no hyperleucocytosis, CR after 1 induction = 3% CR1 patients) didn’t receive 1st line alloSCT but intensive consolidation then a 2nd HD ARAC course; alloSCT was therefore considered at relapse = arm C. Patients without donor proceed to intensive consolidation then 1 or 2 autoSCT (1st after HDM 200 mg/m2 according to randomization, then Bu 16 mg/kg over 4d + HDM 140 mg/m2 for all patients) = arms A + B; they were combined for analysis as no difference was observed for DFS and OS. Actual results concern 532 patients with 15 months follow-up (A + B = 367; M = 111; m = 54). Median age was different between 3 groups (A + B = 46; M = 40; m = 54) as no difference was observed regarding leukocytosis or cytogenetic subgroups: favorable (t8;21) or inv16: A + B = 15%; M = 11%; m = 11%), intermediate (A + B = 72%; M = 78%; m = 67%), defavorable (5, 7, complex, 11q23 except t(9;11) or 3q; A + B = 13%; M = 11%; m = 22%). Conventional alloSCT results in better 2y DFS than autoSCT arms (M 71% vs A+B 52%, p=0,007) thought 2y OS advantage remains non significant (M 77% vs A+B 68%, p=0,06) as toxic death rate is higher (36% all deaths in arm M vs 14 % in arms A + B). No significant difference was observed between conventional alloSCT and NST (2y DFS 62%, OS 68%). Advantage for NST over autoSCT arms was non significant for DFS (p=0,24) and OS. Same results are obtained if considering only patients aged > 50: 2y EFS (m 62% vs A+B 50%, p=0,27) and OS (m 68% vs A+B 65%). After NST, toxicity accounts for 25% deaths, as relapse rate is 40% at 2y with no late relapse thereafter (vs 48 % at 2y and 61 % at 4y in arms A + B). In conclusion: 1) conventional alloSCT remains the best consolidation treatment for patients ≤ 50 with AML in CR1 despite higher toxicity; 2) NST after intensive consolidation seems promising: for older patients as toxicity is lower than conventional alloSCT, as few late relapse are observed in comparison with chemotherapy or autoSCT approaches; 3) NST may extend use of alternative sources of allogeneic hematopoietic stem cells to propose alloSCT approach for the majority of patients ≤ 60 with AML in CR1. Data with more than 2 years follow-up will be presented.

Single Versus Tandem High Dose Therapy (HDT) Supported with Autologous Blood Stem Cell (ABSC) Transplantation Using Unselected or CD34-Enriched ABSC: Long-Term Results of a Two by Two Designed Randomized Trial in 225 Young Patients with Multiple Myeloma (MM). for the Group “Myelome-Autogreffe”, Caen, Creteil, Limoges, Paris, Strasbourg, France.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2320-2320 ◽  
Author(s):  
Jean-Paul Fermand ◽  
Kristell Desseaux ◽  
Jean Pierre Marolleau
Keyword(s):  
Randomized Trial ◽  
Disease Progression ◽  
Conflicts Of Interest ◽  
Autologous Blood ◽  
Prospective Trial ◽  
Early Death ◽  
Long Term Results ◽  
High Dose ◽  
Significant Difference

Abstract Abstract 2320 Poster Board II-297 In 1996, we initiated a multicenter prospective trial where patients aged under 56 with newly diagnosed symptomatic MM were randomly assigned up-front to receive either a single HDT (HDT1) or two sequential HDT (HDT2). In addition, all patients were independently randomized to be transplanted with unselected ABSC (unselected arm) or CD34-enriched ABSC (CD34 arm). We presented here updated data of this factorial 2*2 design trial, based on a median follow-up of 123 months.In all cases, patients first received one or 2 courses of high dose steroid containing regimens and ABSC were thereafter mobilized by cytoxan (CTX) (4 g/m2) and lenograstim (10 mg/kg/d). When appropriate (CD34 arm), part of collected ABSC were selected using the Isolex®300i system. The selection procedure resulted in a median purity of 95% (65-100) and in a more than two log tumor cell depletion. In the HDT1 arm, HDT was preceded by 3 monthly courses of a VAD-like regimen and combined a multi-drug regimen (carmustine, etoposide, melphalan 140 mg/m2 (MLP 140) and CTX 60 mg/kg) with a TBI (12 grays in 6 fractions). Patients treated in the HDT2 arm received MLP 140 alone (always supported by unselected ABSC) followed 2 to 3 months later by a second MLP 140 combined with etoposide (30 mg/kg) and 12-gray TBI. In both arms, TBI including HDT were supported with unselected or CD34 enriched ABSC. Two hundred and twenty-five patients were included in the study. Baseline characteristics of the four groups were close. All analyses were performed in intent to treat basis. In HDT groups, treatment completion rates were satisfactory, with 6/112 transplants not performed in the HDT1 group (allotransplant n=1, refusal n=1, mobilisation failure n=1, early death due to disease progression n=3) and 9/113 second transplant not performed in the HDT2 group (allotransplant n=2, mobilisation failure n=3, relapse post first transplant n=1, early death due to disease progression n=3). In the HDT1 and HDT2 groups, median time to TBI-including transplant was 4 months and 4.5 months, respectively.Present analysis did not show any significant difference in terms of early mortality, disease response and outcome of patients included in the two HDT groups. Early death rates (within 9 months post randomization, including toxic deaths and fatal progressive diseases) were 12% and 7% in the HDT1 and the HDT2 arms, respectively. At one year post-randomization, 32 (35 %) patients in the HDT1 and 32 (37 %) patients in the HDT2 groups were still in unmaintained CR or VGPR. The 2 OS curves were not statistically different (p= 0.60 by the log rank test), neither the EFS curves (p= 0.61). There was no significant interaction between selection CD34 and HDT in terms of outcomes. There was no evidence for benefit of CD34 selection as compared to the use of unselected ABSC. Of note, in the CD34 selected group, incidence of severe infections was increased. In conclusion, with a 10-years median follow-up, results of this randomized trial did not show any significant benefit of single HDT versus tandem HDT. Disclosures: No relevant conflicts of interest to declare.

Bortezomib With High-Dose Melphalan, Arsenic Trioxide, and Ascorbic Acid In a Preparative Regimen For Multiple Myeloma: 5-Year Follow Up

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5547-5547
Author(s):  
A. Megan Cornelison ◽  
Yvonne Dinh ◽  
Manish Sharma ◽  
Nina Shah ◽  
Qaiser Bashir ◽  
...  
Keyword(s):  
Board Of Directors ◽  
High Dose ◽  
Refractory Disease ◽  
Advisory Committees ◽  
Significant Difference ◽  
Preparative Regimen ◽  
First Remission ◽  
High Dose Melphalan

Abstract Background Bortezomib and high-dose melphalan was associated with a higher complete remission (CR) rate in a phase II trial by the IFM group. Four doses of bortezomib 1 mg/m2 IV were given on days -6, -3, +1 and +4. (Roussel M et al. Blood 2010. 115:32-37).In a randomized phase II trial we reported that the addition of bortezomib to a preparative regimen of arsenic trioxide (ATO), ascorbic acid (AA), and melphalan followed by autologous hematopoietic stem cell transplantation (auto-HSCT) failed to demonstrate a statistically significant improvement in CR rate or survival in patients (pts) with newly diagnosed or relapsed multiple myeloma (Sharma M et al. Cancer. 118:2507-15).This study was limited by a short follow up (median 36 months) and inclusion of pts with relapsed and refractory disease. In this retrospective analysis, we evaluated the long-term (5-years) impact of the addition of bortezomib to this preparative regimen in pts who underwent auto-HCT in first remission or with primary refractory disease. Methods Forty-three pts underwent auto-HCT in first remission or with primary refractory disease. All patients received ATO 0.25 mg/kg intravenously on days -9 to -3, AA 1000 mg intravenously on days -9 to -3, and melphalan 100 mg/m2 intravenously on days -4 and -3. Pts received either no bortezomib (n=13), or bortezomib at a dose of either 1 mg/m2 of 1.5 mg/m2 on days -9, -6, and -3. The primary endpoint was CR rate and secondary endpoints were progression free survival (PFS) and overall survival (OS). Results Pt characteristics are shown in the attached Table. The median follow-up for all surviving pts was 61.4 months (range, 15-80 months). Pts in the bortezomib and non-bortezomib arms were matched for age, gender, high-risk cytogenetic abnormalities, time to auto-HSCT, use of bortezomib in induction, and disease burden at auto-HSCT (Table). Only 5 (17%) pts in the bortezomib and 4 (30%) in the non-bortezomib group received maintenance therapy. There was no significant difference in the time to neutrophil engraftment or treatment-related mortality TRM between the bortezomib and non-bortezomib groups. The CR rate in the bortezomib group and the non-bortezomib group was 20% and 53%, respectively (p=0.03). There was no significant difference in rates of CR + very good partial remission (VGPR), or CR + VGPR + partial remission (PR) between the bortezomib and non-bortezomib groups (p=0.72 and 1.00, respectively). The median PFS in the bortezomib group and the non-bortezomib group was 25.4, and 40.0 months, respectively (p=0.13, Figure 1). The median OS was 61.6 months in the bortezomib group and not reached in the non-bortezomib group (p=0.22, Figure 2). There was no significant impact of high-risk cytogenetics, lactic dehydrogenase (LDH) or b2 microglobulin levels, or maintenance therapy on PFS or OS. Conclusions After long-term follow up of 5 years, the addition of bortezomib to a preparative regimen of ATO, AA, and high-dose melphalan did not result in a significant improvement in CR rate, PFS, or OS. The lack of benefit with bortezomib may be due to the inclusion of ATO and AA in the regimen, or the schedule of bortezomib, which was only given before melphalan. Disclosures: Shah: Celgene: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Qazilbash:Celgene: Membership on an entity’s Board of Directors or advisory committees Other; Millenium: Membership on an entity’s Board of Directors or advisory committees, Membership on an entity’s Board of Directors or advisory committees Other.

A Randomized Phase II Trial of High-Dose Melphalan, Ascorbic Acid and Arsenic Trioxide with or without Bortezomib in Multiple Myeloma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3320-3320 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima M. Saliba ◽  
Matteo Pelosini ◽  
Chitra M Hosing ◽  
Floralyn L Mendoza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Ascorbic Acid ◽  
Arsenic Trioxide ◽  
Phase Ii Trial ◽  
High Dose ◽  
Randomized Phase Ii ◽  
Significant Difference ◽  
Preparative Regimen ◽  
High Dose Melphalan

Abstract Background: There is a role of novel preparative regimens to further improve the outcome after high-dose chemotherapy and autologous hematopoietic stem cell transplantation (ASCT) in multiple myeloma. Arsenic trioxide (ATO) has synergistic activity with melphalan and ascorbic acid (AA) both in vitro and in vivo, and this 3-drug combination was found to be safe and feasible in both conventional and high-dose settings. Bortezomib, a proteasome inhibitor, is an active agent in newly diagnosed or relapsed multiple myeloma in conventional therapy setting. We conducted a randomized phase II trial to determine the safety and efficacy of a combination of ATO, AA and melphalan with or without bortezomib as preparative regimen in patients with myeloma. Methods: Sixty patients were enrolled and 58 patient received ASCT between October 2006 and September 2007. One patient developed respiratory failure and another developed extensive pulmonary embolism after enrollment and did not proceed to ASCT. All 58 evaluable patients received melphalan 100 mg/m2 IV on days -4 and -3, AA 1000 mg/day IV on days -9 to -3 and ATO 0.25 mg/kg IV on days -9 to -3. Patients were randomized to 3 arms; no bortezomib (arm 1), bortezomib 1 mg/m2 on days -9, -6 and -3 (arm 2), and bortezomib 1.5 mg/m2 on days -9, -6 and -3 (arm 3). Patients were also asked to fill out a standardized Quality of Life (QOL) questionnaire at enrollment and at 6 months post-ASCT. Results: Median age of patients in arms 1, 2 and 3 were 61, 59 and 64 years, respectively (p=0.08). Median interval between diagnosis and ASCT were 12.2, 9.6 and 8.8 months, respectively (p=0.3). Cytogenetic abnormalities were detected in 2, 5 and 8 patients in arms 1, 2 and 3, respectively (p=0.08). With a median follow up of 11.4 months (range 5 to 20) post ASCT in surviving patients, cumulative non-relapse mortality was1.7%. Grade 3–4 toxicity was seen in 6 patients in arm 1 (mucositis 3, dyspnea 1, acute renal failure 1, pleural effusion 1), 6 patients in arm 2 (mucositis 3, diarrhea 1, pneumonia 1 and hydronephrosis 1) and 6 patients in arm 3 (pulmonary edema 2, mucositis 1, intestinal obstruction 1, low back pain 1, elevated transaminases 1) (p=0.9). The most common adverse events were nausea, diarrhea and pedal edema. Grade 1–2 weight gain due to fluid retention was seen in 84, 70 and 95% of patients in arms 1, 2 and 3, respectively (p= 0.1). Median time to neutrophil engraftment (ANC >500/dl) was 10 days in each arm. Complete response rates in arms 1, 2 and 3 were 26, 10 and 16%, respectively (0=0.4). Kaplan-Meiers estimates of progression-free survival (PFS) and overall survival (OS) are shown in Figures 1 and 2. Median PFS and OS have not been reached. There was no significant difference in CR, PFS or OS between the 3 arms (p = 0.4, 0.62 and 0.4, respectively). Relapsed disease at ASCT (p=0.003), >12 months interval between diagnosis and ASCT (p=0.05), and cytogenetic abnormalities at diagnosis (p=0.005) predicted a shorter PFS. On a subset analysis, there was no significant difference in PFS or OS between the 3 arms in patients undergoing ASCT in first remission. Fifty-patients submitted their responses to the QOL questionnaire. More patients at 6-month post ASCT reported better overall health (56% vs.12%, p=0.0001). In contrast, more patients at study enrollment reported moderate to severe pain (44% vs. 27%, p=0.09) and debilitating emotional problems (42% vs. 23%, p=0.07). Conclusions: Adding bortezomib to ATO, AA and high dose melphalan is safe and well tolerated as preparative regimen for ASCT in patients with multiple myeloma. Patients with chromosomal abnormalities were predominantly treated in the bortezomib arms without an adverse impact on PFS or OS. Overall QOL indicators showed improvement at 6-month post ASCT. Longer follow up is needed to assess the efficacy of this combination. FIGURE 1 FIGURE 1. FIGURE 2 FIGURE 2.

Mature results of a randomized trial of two doses of cisplatin for the treatment of ovarian cancer. Scottish Gynecology Cancer Trials Group.

1996 ◽  
Vol 14 (7) ◽  
pp. 2113-2119 ◽  
Author(s):  
S B Kaye ◽  
J Paul ◽  
J Cassidy ◽  
C R Lewis ◽  
I D Duncan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Death Rate ◽  
Randomized Study ◽  
Advanced Ovarian Cancer ◽  
High Dose ◽  
Optimal Balance ◽  
Significant Difference ◽  
First Results ◽  
To Receive

PURPOSE In 1992, we reported the first results of a randomized study in ovarian cancer, comprising two doses of cisplatin and indicated a significant difference (P = .0008) in median survival. Four years later, we now describe the results of this trial. PATIENTS AND METHODS After a median follow-up of 4 years and 9 months, 115 of 159 cases of advanced ovarian cancer, originally randomized to receive six cycles of cyclophosphamide 750 mg/m2 and either a high dose (HD) of 100 mg/m2 cisplatin or a low dose (LD) of 50 mg/m2 (LD) cisplatin, have now died. RESULTS The overall survival for HD and LD patients is 32.4% and 26.6%, respectively, and the overall relative death rate is 0.68 (P = .043). This represents a reduction in overall benefit with longer follow-up compared with the first 2 years (relative death rate of 0.52). Toxicity, particularly neurotoxicity, is still evident in the fourth year (10/31 on HD compared with 1/24 on LD). CONCLUSION Our recommended dose of cisplatin in combination schedule is therefore 75 mg/m2, representing the optimal balance between efficacy and toxicity.

Therapy-Related Myelodysplasia and Secondary Acute Myelogenous Leukemia After High-Dose Therapy With Autologous Hematopoietic Progenitor-Cell Support for Lymphoid Malignancies

2000 ◽  
Vol 18 (5) ◽  
pp. 947-947 ◽  
Author(s):  
Ivana N. M. Micallef ◽  
Debra M. Lillington ◽  
John Apostolidis ◽  
John A. L. Amess ◽  
Michael Neat ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Progenitor Cell ◽  
Myelogenous Leukemia ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
High Dose Therapy ◽  
Hematopoietic Progenitor ◽  
Acute Myelogenous ◽  
Cell Support

PURPOSE: To evaluate the incidence of and risk factors for therapy-related myelodysplasia (tMDS) and secondary acute myelogenous leukemia (sAML), after high-dose therapy (HDT) with autologous bone marrow or peripheral-blood progenitor-cell support, in patients with non-Hodgkin’s lymphoma (NHL). PATIENTS AND METHODS: Between January 1985 and November 1996, 230 patients underwent HDT comprising cyclophosphamide therapy and total-body irradiation, with autologous hematopoietic progenitor-cell support, as consolidation of remission. With a median follow-up of 6 years, 27 (12%) developed tMDS or sAML. RESULTS: Median time to development of tMDS or sAML was 4.4 years (range, 11 months to 8.8 years) after HDT. Karyotyping (performed in 24 cases) at diagnosis of tMDS or sAML revealed complex karyotypes in 18 patients. Seventeen patients had monosomy 5/5q−, 15 had −7/7q−, seven had −18/18q−, seven had −13/13q−, and four had −20/20q−. Twenty-one patients died from complications of tMDS or sAML or treatment for tMDS or sAML, at a median of 10 months (range, 0 to 26 months). Sixteen died without evidence of recurrent lymphoma. Six patients were alive at a median follow-up of 6 months (range, 2 to 22 months) after diagnosis of tMDS or sAML. On multivariate analysis, prior fludarabine therapy (P = .009) and older age (P = .02) were associated with the development of tMDS or sAML. Increased interval from diagnosis to HDT and bone marrow involvement at diagnosis were of borderline significance (P = .05 and .07, respectively). CONCLUSION: tMDS and sAML are serious complications of HDT for NHL and are associated with very poor prognosis. Alternative strategies for reducing their incidence and for treatment are needed.

scholarly journals Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study

Blood ◽  
2016 ◽  
Vol 128 (4) ◽  
pp. 594-602 ◽  
Author(s):  
Tilmann Bochtler ◽  
Ute Hegenbart ◽  
Christina Kunz ◽  
Axel Benner ◽  
Christoph Kimmich ◽  
...  
Keyword(s):  
High Dose ◽  
Al Amyloidosis ◽  
Prognostic Impact ◽  
Favorable Prognosis ◽  
Cytogenetic Aberrations ◽  
Key Points ◽  
Long Term Follow Up ◽  
High Dose Melphalan

Key Points Translocation t(11;14) confers a favorable prognosis in AL amyloidosis patients treated with HDM.

Medulloblastoma: freedom from relapse longer than 8 years — a therapeutic cure?

1991 ◽  
Vol 75 (4) ◽  
pp. 575-582 ◽  
Author(s):  
Mark G. Belza ◽  
Sarah S. Donaldson ◽  
Gary K. Steinberg ◽  
Richard S. Cox ◽  
Philip H. Cogen
Keyword(s):  
Medical Center ◽  
Survival Rates ◽  
Adjunctive Treatment ◽  
High Dose ◽  
Content Type ◽  
Significant Difference ◽  
Long Term Follow Up ◽  
Fine Print

✓ Seventy-seven patients presenting with medulloblastoma between 1958 and 1986 were treated at Stanford University Medical Center and studied retrospectively. Multimodality therapy utilized surgical extirpation followed by megavoltage irradiation. In 15 cases chemotherapy was used as adjunctive treatment. The 10- and 15-year actuarial survival rates were both 41% with an 18-year maximum follow-up period (median 4.75 years). There were no treatment failures after 8 years of tumor-free survival. Gross total removal of tumor was achieved in 22 patients (32%); the surgical mortality rate was 3.9%. No significant difference was noted in the incidence of metastatic disease between shunted and nonshunted patients. The classical form of medulloblastoma was present in 67% of cases while the desmoplastic subtype was found in 16%. Survival rates were best for patients presenting after 1970, for those with desmoplastic tumors, and for patients receiving high-dose irradiation (≥ 5000 cGy) to the posterior fossa. Although early data on freedom from relapse suggested a possible beneficial effect from chemotherapy, long-term follow-up results showed no advantage from this modality of treatment. The patterns of relapse and survival were examined; 64% of relapses occurred within the central nervous system, and Collins' rule was applicable in 83% of cases beyond the period of risk. Although patients treated for recurrent disease could be palliated, none were long-term survivors. The study data indicate that freedom from relapse beyond 8 years from diagnosis can be considered as a cure in this disease. Long-term follow-up monitoring is essential to determine efficacy of treatment and to assess survival patterns accurately.

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