Outcome after second stem cell transplantation for relapsed multiple myeloma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8118-8118 ◽  
Author(s):  
L. Simpson ◽  
R. Verma ◽  
S. Kumar ◽  
M. Lacy ◽  
A. Dispenzieri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Standard Of Care ◽  
Best Response ◽  
High Risk Disease ◽  
Viable Approach ◽  
Median Interval

8118 Background: Autologous stem cell transplantation (ASCT) improves survival and remains the standard of care for patients with newly diagnosed myeloma considered eligible for transplant. However, ASCT is not curative and patients relapse after a median interval of 24–30 months. While new therapeutic options have become available for relapsed MM, repeat ASCT remains an option especially when previously collected stem cells are available. The outcome of pts going to a second SCT in the relapsed setting has not been studied extensively. Methods: We identified pts with myeloma who received a second SCT from a prospectively maintained database. Planned tandem ASCTs were excluded. 56 pts received a second SCT for relapsed MM, including 11 allogeneic SCTs. Among the 45 second ASCTs, 5 were followed by reduced intensity allogeneic SCT and were analyzed with the allogeneic group. Results: The median age at second ASCT was 60.2 yrs (range, 41.3–74.4) and 27 (68%) were males. The median time to second ASCT from diagnosis, first ASCT and relapse were 47.4 mos (22.8–158.6), 36.3 mos (13.5–129.8) and 7.2 mos (1–32) respectively. Among patients receiving second APBSC, 14 (35%) patients were alive with a median follow up of 10.5 mos (1–45 mos). All patients received melphalan conditioning. The median time to neutrophil engraftment was 15 days and platelet engraftment was 16 days. The median hospitalization was 4 days (range 0–33) and there was one transplant related death in the group. The best response included 13 pts with CR (33%), 4 with VGPR (10%), and 19 with PR (48%). MM has relapsed in 22 (55%) pts with a median PFS of 12.5 mos from second ASCT. The median estimated OS from diagnosis, first ASCT and second ASCT were 100.5 mos, 65.9 mos, and 30.6 mos respectively. Among the 16 pts receiving allogeneic SCT, 8 pts (50%) were alive at analysis with a median PFS and OS from transplant of 17.9 mos and 33.5 mos respectively. Conclusions: Second ASCT as salvage therapy for relapsed MM is a viable approach and has a favorable outcome in this selected group of patients. The toxicity, engraftment kinetics, hospitalization and the response rates are comparable to patients undergoing initial ASCT. Allogeneic SCT with or with out a preceding ASCT results in comparable survival in selected patients with high risk disease. No significant financial relationships to disclose.

Immunotherapy with Rituximab after Peripheral Blood Stem Cell Transplantation for Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5232-5232
Author(s):  
Celso Mitsushi Massumoto ◽  
Edilson Pinheiro Junior ◽  
Otávio C.G. Baiocchi ◽  
Ronald Pinheiro ◽  
Adelson Alves
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Clinical Characteristics ◽  
Residual Disease ◽  
High Dose

Abstract Introduction: autologous stem cell transplantation is a potentially curative or may augment the time to progression in Multiple Myeloma (MM) patients. The immunotherapy with rituximab may help control the minimal residual disease after high dose chemotherapy. Twenty percent (20%) of Multiple Myeloma patients express the CD20+ protein and can be target for immunotherapy. Objective: The aim of this study was to evaluate the use of rituximab after autologous stem cell transplantation for Multiple Myeloma. Patients and Methods: eight patients (4 male) with a median age of 53 (range 43–59) years diagnosed with MM. All of them had received at least one previous regimen were enrolled in the protocol study. All patients signed the consent form. Patients in relapse received a salvage regimen with C-VAD n=2 (cyclofosfamide 4 g/m2 e vincristine 0.4 mg/d (d 1–4), doxorrubicin 0.9 mg/m2 (d1-4) e dexametasone 40 mg (d1-4; 9-12; 17–22) or cyclofosfamide (1OO mg/kg, n=7) followed by stem cell harvesting. The preparative regimen was Busulfan 12 mg/kg and cyclofosfamide 120 mg/kg or Melphalan 200mg/m2. Rituximab at a dose of 375mg/m2 weekly x 4 was given every 6 months for 2 years after SCT. The clinical characteristics of the patients are shown on Table 1. Results: the median time to ANC and platelets engraftment was 11 (range 8–12) and 26 (range 17–35) days. Patients have been in CR at a median time of 11 months follow-up. Minor Rituximab-associated toxicities were seen:rigor, fever and short of breath that were controlled with acetaminophen and diphenidramine. Conclusion: the Rituximab given after autologous stem cell transplantation is safe in Multiple Myeloma patients and may prolong time to disease progression. A randomized study is required to evaluate the role of rituximab after ASCT. Table 1 - Clinical Characteristics of Patients Patients Age/gender Status Pre- BMT Status Post- BMT Salvage Tx Prep. regimen ANC/Platelets X1000 MM3/ml Follow-up (months) FRC 57/M PR PR C-VAD BU+MEL 12/28 EXPIRED MB 52/F CR1 CR1 C-VAD BU+MEL 12/60 EXPIRED AM 52/F PR PR C-VAD BU+MEL 9/26 EXPIRED IM 54/M PR CR Cyx2 BU+MEL 12/21 ALIVE GAD 50/F PR CR Cyx2 BU+MEL 12/35 ALIVE SCM 59/M CR CR Cyx2 BU+MEL 10/17 ALIVE MAD 63/F CR CR C-VAD MELPHALAN 12/25 ALIVE JFC 51/M CR CR C-VAD BU+MEL 12/18 ALIVE

Impact of Allogeneic Stem Cell Transplantation as Salvage Therapy After T315I Mutation Detection in Chronic Myeloid Leukemia (CML) and Ph+ Acute Lymphoblastic Leukemia (ALL) Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 645-645
Author(s):  
Franck Emmanuel Nicolini ◽  
Wei Zhou ◽  
Giovanni Martinelli ◽  
Michael J. Mauro ◽  
Andreas Hochhaus ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Mutation Detection ◽  
Treatment Start ◽  
T315i Mutation ◽  
Tki Treatment

Abstract Abstract 645 Background: The development of a BCR-ABL T315I mutation is associated with a poor prognosis and limited therapeutic options. The impact of the mutation on the outcome of stem cell transplantation (SCT) is unknown. Aim: To describe the overall survival (OS) of CML patients in any phase and Ph+ ALL patients who received an allogeneic SCT after developing a T315I mutation after exposure to tyrosine kinase inhibitors (TKI). Methods: We conducted a retrospective, multi-center observational study of 222 CML and de novo Ph+ ALL patients who developed a T315I mutation between 1999 and 2008. Data from the medical records of 33 patients (15% of all patients in the registry) from 9 countries (USA, France, Italy, Germany, Denmark, Singapore, and the UK) who received an allogeneic SCT after T315I mutation detection were included in this study. Results: At the time of diagnosis, the median age was 39 years (range, 16-67); 70% were male; 26 patients were in CML CP, 1 in CML AP, 2 in CML BC, and 4 had Ph+ ALL. The median time between diagnosis and TKI treatment start was 3 months (range, 0-125), between diagnosis and T315I mutation detection was 28 months (range, 3-131), and between TKI treatment start and T315I mutation detection was 19 months (range, 2-64). Five (15%) patients had TKIs as frontline therapy. At the time of T315I detection, 10 patients were in CML CP, 7 in CML AP, 12 in CML BC, and 4 had Ph+ ALL. Hydroxyurea (alone or combined with other treatments) was the most common 1st line treatment (55%) after T315I mutation detection. The median time from T315I mutation detection to SCT was 3 months (range, 0.3-28). At the time of transplant, the median age was 42 years (range, 22-68); 8 patients were in CML CP, 7 in CML AP, 14 in CML BC and 4 had Ph+ ALL; 32 patients received 1 SCT and 1 received 2 SCTs after T315I mutation detection. The source of stem cells was peripheral blood (53%), bone marrow (35%), cord blood (6%), and unknown (6%). 82% were matched donor and 18% were unmatched. The median follow-up time from SCT was 7 months and 15 (55%) patients had died by their last follow-up. The OS of CML CP and CML AP patients was much better than CML BP and Ph+ ALL patients (Fig. 1; logrank, p=.050). The 1-yr OS rates (95% CI) from SCT were 69% (21-91%) for CML CP, 71% (26-92%) for CML AP, 16% (3-39%) for CML BC, and 33% (1-77%) for Ph+ ALL; and the 3-yr OS rates (range) was 69% (21-91%) for CML CP, 71% (26-92%) for CML AP, 0 for CML BC, and 0 for Ph+ ALL. Conclusion: These results suggest that the survival of patients harboring a T315I mutation and treated with allogeneic SCT is dependent on the disease phase at the time of SCT. SCT is the treatment of choice for these CML patients, particularly those in CP and AP.Fig. 1.Overall survival from Allogeneic SCTFig. 1. Overall survival from Allogeneic SCT Disclosures: No relevant conflicts of interest to declare.

Long term follow up of patients with locally advanced triple negative breast cancer treated with adjuvant high dose chemotherapy and autologous stem cell transplantation: A single center experience.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e12590-e12590
Author(s):  
Sani Mohammed Bukari ◽  
Muhammad Usman ◽  
Judith Abrams ◽  
Voravit Ratanatharathorn ◽  
Joseph P. Uberti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
High Risk ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Locally Advanced ◽  
Standard Of Care ◽  
High Dose Chemotherapy ◽  
High Dose

e12590 Background: Adjuvant high dose chemotherapy (HDC) with Autologous Hematopoietic Stem Cell Transplantation (AuSCT) as part treatment of high risk locally advanced breast cancer has remained controversial. Multiple trials reported disease free survival (DFS) without Overall survival (OS) resulting in its abandonment in early 2000s. However, post hoc analysis of these trials consistently reported DFS and OS benefit in young and triple negative breast cancer (TNBC) subgroups. This has not been re-evaluated till date. Recent European registry reports coupled with improved transplant related mortality (TRM) and still poor out-come of standard of care in TNBC subgroup has generated renewed interest. We report long term out-come of locally advanced high risk TNBC treated with HDC and AuSCT treated in Karmanos Cancer Institute from 1995 to 2001 Methods: Majority of the patients were treated with Adriamycin and Taxane based induction chemotherapy. Patients without evidence of metastatic disease proceeded to HDC and AuSCT using Carmustine 600mg/sqm Cyclophosphamide 5.6gm/sqm and Cisplatin 165mg/sqm (STAMP 1 regimen). This is followed with loco- regional radiation per protocol. Results: 72 hormone negative patients with Lymph Node(LN) > 4 or inflammatory breast cancers were selected from 576 treated for advanced or metastatic breast cancer. 33 patients were TNB with HER2 status of 39 patients unknown. Median time from diagnosis to stem cell transplantation was 6 months. Median age at diagnosis was 47yrs. Mean LN involvement was 9 with 90% having (4-20) LN positivity. With median follow up of 16 years,10yrs DFS and OS were both 62.5%. Median follow up for DFS and OS was not reached.TRM was 9% mostly from pulmonary toxicity. Conclusions: This study of locally advanced high risk TNBC treated with adjuvant HDC and AuSCT have high 10yr OS of 62.5% compared to current standard of care. With the current improvement in TRM, reevaluation of this strategy through clinical trials in this subgroup whose outcome remain poor is reasonable.

Imatinib Mesylate (IM), Is an Alternative to Donor Lymphocyte Infusion (DLI) for Chronic Myelogenous Leukemia (CML) in Relapse after Allogeneic Stem Cell Transplantation: A 3-Year Follow-Up Report, on the Behalf of the Société Française de Greffe de Moëlle et de Thérapie Cellulaire (SFGM-TC) and the France Intergroupe de la Leucémie Myéloïde Chronique (Fi-LMC).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1017-1017
Author(s):  
Cecile Pautas ◽  
Frank Nicolini ◽  
Pascal Cony-Makhoul ◽  
Stephane Giraudier ◽  
Dominique Bories ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Imatinib Mesylate ◽  
Cell Transplantation ◽  
Median Time ◽  
Allogeneic Stem Cell Transplantation ◽  
Molecular Remission ◽  
Allogeneic Hsct ◽  
Blastic Phase

Abstract DLI are an efficient treatment for CML in relapse after allogeneic stem cell transplantation, with 60 to 70% of complete response. However, major side effects such has graft-versus-host disease (GVHD) or pancytopenia are frequently observed after this treatment. Imatinib mesylate has also been shown to be effective in a such situation (Blood 2002, 100 (5): 1590–95). In the present study, we report the French experience, with a 3 years median follow-up of 26 patients in relapse of CML after allograft (21 sibling, 4 unrelated, 1 cord blood transplantations). At time of treatment with IM, twenty patients were in chronic phase and 5 only were in molecular relapse, while 4 patients were in blastic phase. Median time from graft to relapse was 36 months (3–132 months) and the median time from relapse to Imatinib was 15 months ( 1–96 months). Ten patients had already received DLI, 14 patients Interferon. Only 6 patients had no treatment prior to IM. With a median follow-up of 32 months (16–44 months), 19 patients are alive and 5 died. The majority of patients in chronic (19/20) phase are alive. At time of last follow-up : Three (11%) patients fail to respond to IM, 2 (8%) have a partial response, 12 (46%) are in CCR with 9/12 in molecular remission, and 4 (15%) patients present relapse (1 blastic phase, 3 molecular relapse). Eleven patients are evaluable for VNTR chimerism, 8(72%) achieved full donor chimerism at last follow-up. IM was well tolerated, and 2 GVHD reactivations were observed but 8 (42%) patients experienced cytopenias requiring drug modulation or withdrawal, and two grade IV toxicities (muscle cramps, cardiomyopathy). Six patients stopped IM (2 toxicities, 4 long term molecular remissions). Four of these patients experienced molecular relapse (3 after 12 months, 1 at 3 months). One patient achieved molecular remission after a new challenge with IM. In conclusion, Imatinib mesylate is efficient and safe treatment for CML in relapse after allogeneic HSCT without reactivating GVHD, and is able to restore full donor chimerism in a majority of responsive patients. A complete and sustained molecular response is obtained in about one third of patients, however molecular relapse is frequent after IM withdrawal. The place of IM and/or DLI for CML in relapse after allogeneic HSCT needs to be addressed prospectively and requires a randomized trail.

scholarly journals Upfront Autologous Stem Cell Transplantation for Newly Diagnosed Elderly Multiple Myeloma (MM) Patients: A Prospective Multicenter Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1989-1989
Author(s):  
Laurent Garderet ◽  
Cyrille Touzeau ◽  
Anne-Marie Stoppa ◽  
Denis Caillot ◽  
Lionel Karlin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Board Of Directors ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Research Funding ◽  
Newly Diagnosed ◽  
Advisory Committees

Abstract Introduction: Previous trials have shown that autologous stem cell transplantation (ASCT) is superior to conventional chemotherapy in terms of remission rate and PFS in younger MM patients. Concerns about toxicity and potential efficacy of ASCT in older MM patients lead most centers to limit ASCT indications to patients aged <65 years. However, at the era of novel induction regimens, and because of better patient selection and supportive care, ASCT may prove to be a valid treatment option even in older MM patients. Therefore, some investigators are questioning the widely used 65 years age limit. Patients and Methods: We prospectively analyzed the outcomes of 56 consecutive MM patients who had received ASCT between September 2012 and September 2014 in 6 institutions in France (protocol ClinicalTrials.gov Identifier: NCT01671826). Patients were newly diagnosed MM. For induction therapy, all patients received a bortezomib-based induction regimen (VD, VTD, VCD, or VRD, 4 to 6 cycles) according to center's local guidelines. Mobilization was performed with G-CSF or G-CSF+cyclophosphamide and plerixafor whenever needed. High-dose chemotherapy consisted of either 140 mg/m2 or 200 mg/m2 Melphalan. A short two months consolidation phase post ASCT was allowed (lenalidomide-dexamethasone, VD, VTD, VCD or VRD). No maintenance treatment was given. Response, disease progression and relapse were defined according to the IMWG uniform response criteria. All patients signed an informed consent form according to the EBMT guidelines. Results: At time of diagnosis, median age was 67 (range, 64-74) years with 23% of patients being >70 years. There were 30 males and 26 females. The immunoglobulin subtype was IgG (n=29), IgA (n=15), light chain (n=10), other (n=2). The Salmon and Durie stage was III in 89% of cases (n=47), and the ISS score was I (n=18; 35%), II (n=19; 37%), III (n=14; 27%). Patients had high risk cytogenetics features (t(4;14) and/or del17p) in 9 cases (16%). 10% of patients had a serum creatinine level >176 micromol/L. None of the patients underwent hemodialysis. The Sorror comorbidity score was 0 (34), 1 (6), 2 (2), 3 (6), 6 (1), unknown (7). The median age at time of ASCT was 68 years, and the median time from diagnosis to ASCT was 5 months. In an intention to treat analysis, out of 56 patients, 6 patients could not proceed to ASCT because of an early infectious death (n=1), serious comorbidity (n=2), disease refractoriness to induction (n=1), and failure to collect an adequate PBSC graft (n=2). A median of 5.31x106/Kg CD34+ cells could be collected. Disease status at time of ASCT was: CR (n=12; 24%), VGPR (n=19; 38%), PR (n=17; 34%), and SD/non-responding (n=2; 4%). The conditioning regimen consisted of 140mg/m² melphalan in 18 cases (36%) and 200mg/m2 in 32 patients (64%). Moreover, 4 patients (8%) received a tandem ASCT. The median time for neutrophils and platelets engraftment was 12 days. The day-100 post ASCT non-relapse mortality was 0% and the 2-year NRM was 4.2% (95% CI:[0.3-18.3]). The overall response rate at day 100 was 96% (CR: 34%, VGPR: 47%, PR: 15%, SD/non-responsive: 4%). At 3 months post ASCT, 82% patients were able to receive the planned post ASCT consolidation treatment. After a median follow-up of 12 months, the estimated progression-free (PFS) and overall survival (OS) rates at 2 years were 76% (95%CI: [61.6-94.1]) and 88% (95%CI: [76.7-100]), respectively. The incidences of infectious complications post ASCT, and response rates were comparable between the two melphalan dose levels (p=0.28). However, in the univariate analysis, the 200 mg/m2 melphalan conditioning group showed a better OS rate compared to the 140 mg/m2 group (1-year OS: 100% vs. 67%; p=0.012). Conclusion: These prospective multicenter results indicate that ASCT is a safe and effective treatment modality for elderly, but fit MM patients at the era of novel induction agents. Of note, patients above age 70 did not experience a worse prognosis. Thus, age per se should not be used as an exclusion criterion for ASCT. Longer follow-up data will be presented, but these results already set the frame for a randomized comparison to the non-transplant approaches in this patients' subgroup. Disclosures Garderet: Bristol-Myers Squibb: Consultancy. Touzeau:AbbVie: Research Funding. Stoppa:Janssen: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria. Karlin:Celgene: Honoraria; Janssen: Honoraria; BMS: Honoraria; Amgen: Honoraria; Sandoz: Honoraria, Membership on an entity's Board of Directors or advisory committees. Moreau:Celgene, Janssen, Takeda, Novartis, Amgen: Membership on an entity's Board of Directors or advisory committees.

Ruxolitinib As Pretreatment Before Allogeneic Stem Cell Transplantation For Myelofibrosis

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 392-392 ◽  
Author(s):  
Nicolaus Kröger ◽  
Haefaa Alchalby ◽  
Markus Ditschkowski ◽  
Dominik Wolf ◽  
Gerald Wulf ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Allogeneic Stem Cell Transplantation ◽  
Conditioning Regimen ◽  
Unrelated Donor ◽  
Spleen Size ◽  
Rebound Phenomenon

Abstract Introduction We investigate early outcome after allogeneic SCT in 22 patients – male (n = 13) and female (n = 9) – with myelofibrosis who received ruxolitinib prior to transplantation in order to reduce spleen size and constitutional symptoms. Patients and methods The median age of the patients was 59 years (r: 42 – 74 y) and ruxolitinib was given at doses between 2 x 5 mg (n = 5), 2 x 15 mg (n = 5), and 2 x 20 mg (n = 12) before first (n = 19) or second (n = 3) fludarabine-based reduced intensity conditioning from related (n = 2), and matched (n = 14), or mismatched (n = 6) unrelated donor. Thirteen patients had primary myelofibrosis and 9 post ET/PV myelofibrosis. Before ruxolitinib the patients were classified according to DIPSS as intermediate-1 (n = 3), intermediate-2 (n = 14), or high risk (n = 5). Stem cell source was PBSC (n = 21) or bone marrow (n = 1) with a median CD34+ cell count of 7.1 x 106/kg. Before ruxolitinib 21 patients (96%) had constitutional symptoms and all patients had splenomegaly. The median time from start of ruxolitinib to allogeneic SCT was 133 days (r: 27 – 324) and the median treatment duration was 97 days (r: 20 – 316). Most patients (n = 82%) received ruxolitinib until start of conditioning therapy. Four patients (18%) discontinued ruxolitinib between 28 and 167 days before transplantation due to progressive disease or no response (n = 3) or cytopenia (n = 1). Results At time of transplantation 86% had improvement of constitutional symptoms and 45% had major response (>50% palpable) of spleen size, 28% had response of spleen size which was less than 50%, and 27% had no response or progressive spleen size after ruxolitinib treatment. After discontinuation of ruxolitinib at first day of conditioning regimen no “rebound” phenomenon was seen. One patient transformed to sAML before transplantation despite response of spleen size and constitutional symptoms. After busulfan (n = 16), treosulfan (n = 3), or melphalan (n = 3) dose reduced conditioning no graft failure was observed and the median time for leukocyte and platelet engraftment was 15 days (r: 10 – 66) and 17 days (r: 8 – 122) respectively. Acute GvHD I-IV was seen in 50% of the patients which was severe (III/IV) in 18%. During follow-up 4 patients died, 1 patient with sAML at time of transplant due to relapse on day 102 and 3 patients due to therapy-related mortality. One female patient who received a second unrelated HLA-matched transplantation after treosulfan-based regimen died of CMV pneumonitis on day 75. She did not response to ruxolitinib regarding spleen size and constitutional symptoms. A second patient with iron overload and liver fibrosis died of liver toxicity on day 47. This patient initially responded to ruxolitinib but progressed regarding spleen size prior to transplantation. One patient who responded to ruxolitinib regarding constitutional symptoms and spleen size (< 50%) died of GvHD on day 77. The estimated 1-year OS and PFS was 76% (95% CI: 54 – 98%). Conclusion Ruxolitinib reduces spleen size and constitutional symptoms in the majority of patients before allogeneic stem cell transplantation. Discontinuation of ruxolitinib at start of conditioning did not induce rebound phenomenon and did not negatively impact engraftment after transplantation. Longer follow-up is needed to determine late outcome. Disclosures: Wolf: Novartis: Research Funding.

Successful Autologous Stem Cell Transplantation in Patients with Non-Hodgkin’s Lymphoma over the Age of 70 Years.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5290-5290
Author(s):  
Rushdia Z. Yusuf ◽  
Steve McAfee ◽  
Bimalangshu R. Dey ◽  
Beow Yeap ◽  
Thomas R. Spitzer ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Autologous Stem Cell Transplantation ◽  
Large Cell ◽  
Exclusion Criterion ◽  
Related Mortality

Abstract Autologous stem cell transplantation (SCT) is a potentially curative procedure for patients with relapsed lymphoma (NHL). Over 60% of the cases arise in adults over 60 years of age. We retrospectively analyzed the outcomes of patients &gt;60 years old who received high dose busulfan (Bu) and cyclophosphamide (Cy) and autologous SCT for NHL. Stem cells were mobilized with G-CSF with or without chemotherapy. Patients received a dose-adjusted regimen of Bu 0.8 mg/kg IV (n=17) or 1mg/kg po (n=9) q 6 hours x 14 doses starting on Day -7 and Cy 60 mg/kg IV q day on days -3 and -2. In overweight patients, IV Bu doses were calculated based on ideal body weight and oral Bu doses and Cy doses were calculated on an adjusted body weight. All patients were treated as inpatients and received our usual supportive care including transfusion support, pneumocystis prophylaxis, antiviral prophylaxis, growth factor support and broad-spectrum antibiotic coverage for febrile neutropenia. 26 consecutive patients &gt; 60 with relapsed NHL underwent autologous SCT at Massachusetts General Hospital between 1995 and February 2005. The median age of the population was 66 (range 60–78) years. 17 (65%) of the 26 patients were females. 15 patients had large cell lymphoma, 2 immunoblastic lymphoma, 3 follicular lymphoma, and 6 mixed small cleaved cell and large cell. All patients had recurrent disease; 7 patients were in a CR and 19 patients in a PR at the time of transplant. The median time from diagnosis to transplant was 32 months. All patients engrafted. The median time to absolute neutrophil count &gt; 500/uL was 10 days (range 9–11) days. The median time to platelet count &gt; 50,000/uL unsupported was 15 (range 12–39) days. The 100-day transplant related mortality was 0%. Patients experienced the following serious toxicities: interstitial lung disease (n=1), seizures in a patient with CNS lymphoma (n=1), venoocclusive disease which resolved (n=2), and transient atrial fibrillation (n=3). With a median follow-up of 22 months (range 4 months–9.5 years), the two year overall survival is 63% and two year progression-free survival is 42%. Six patients above the age of 70 years have been transplanted. 100-day transplant related mortality was 0%. With a median follow up of 25 months, all 6 patients are alive and 3 of 6 are progression free. In conclusion, 1) Bu/Cy is a well-tolerated conditioning regimen for patients with NHL above the age of 60 years, including selected patients over the age of 70; 2) Age alone should therefore not be used as an exclusion criterion for autologous SCT.

High Response Rate and Improved Graft-Versus-Host Disease (GVHD) Following Bortezomib as Salvage Therapy after Reduced Intensity Conditioning Allogeneic Stem Cell Transplantation (RIC allo-SCT) for Multiple Myeloma (MM).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1080-1080
Author(s):  
Jean El-Cheikh ◽  
Mauricette Michallet ◽  
Arnon Nagler ◽  
Hugues de Lavallade ◽  
Frank E. Nicolini ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Disease Progression ◽  
Cell Transplantation ◽  
Median Time ◽  
Salvage Therapy ◽  
Chronic Gvhd ◽  
Efficient Treatment ◽  
Disease Response

Abstract Bortezomib has been shown to be an efficient treatment for MM. Similarly, a potent allogeneic graft-versus-myeloma effect can be induced against MM. However, despite progress in terms of transplant-related mortality, a significant proportion of patients may still relapse or progress after RIC-allo-SCT. This retrospective report describes the results of 37 MM patients who received bortezomib (1.3 or 1.0 mg/m2 intravenously, days 1, 4, 8, and 11) as a salvage therapy after progression following RIC-allo-SCT. Median age was 49 years. All patients (100%) received and failed at least one autologous stem cell transplantation prior to RIC allo-SCT. Median time between the initial diagnosis of MM and allo-SCT was 11 (range, 6–96) months. Patients were not treated in a combined autologous/allo-SCT strategy. Before bortezomib initiation, 14 patients (38%) received and failed DLI. Also, 20 patients (54%) received and failed thalidomide (because of disease progression or toxicity). Overall, 32 patients (86%) received bortezomib salvage in progressive disease, while 5 patients (14%) were in PR. Median time between allo-SCT and bortezomib initiation was 20 (range, 1–65) months. At time of bortezomib initiation, the majority of patients (n=26; 70%) did not have any symptoms of chronic GVHD, while 8 patients (22%) had some form of limited chronic GVHD, and 3 patients (8%) had extensive signs. The median number of bortezomib cycles administered was 6 (range, 1–15). Peripheral neuropathy was frequently observeded after bortezomib (n=13; 35%; 4 grade 2 and 9 grade 1). Mild thrombocytopenia not requiring platelets transfusions was observed in 9 cases (24%). Fatigue was also observed in 7 patients (19%). None of the patient had to discontinue the treatment because of a life-threatening adverse event, and no treatment-related toxic deaths were observed. In terms of GVHD, patients did not experience reactivation or worsening of GVHD symptoms. Interestingly, two patients among the three patients with extensive GVHD signs at the beginning of bortezomib experienced a significant improvement and were staged as limited chronic GVHD at last follow-up. In all, 27 patients (73%; 95%CI, 59%–87%) achieved an objective disease response after starting of bortezomib (7 CR, 7 VGPR, and 13 PR). Prior use of thalidomide and/or DLI did not influence disease response to bortezomib. There was also no difference in disease response when using bortezomib in combination or without dexamethasone. With a median follow-up of 9 (range, 3–42) months from bortezomib initiation, 25 patients (68%; 95%CI, 53%–83%) still had a sustained objective disease response (5 CR, 5 VGPR, and 15 PR). Ten patients (27%) died and 27 are still alive with a median overall follow-up after allo-SCT of 80 (range, 18–153) months. The majority of deaths were directly attributed to disease progression (n=8; 80% of all deaths). Most importantly, patients achieving an objective disease response (CR, VGPR or PR) after introduction of bortezomib enjoyed a significantly higher overall survival as compared to non-responding patients (P=0.002). Collectively, these data demonstrate that bortezomib is a safe and potentially efficient option for MM patients failing RIC allo-SCT.

Stem Cell Transplantation with 90yttrium Ibritumomab Tiuxetan(90YIT) in Non-Hodgkin's Lymphoma (NHL): Observations From PET Pre-Treatment Imaging and Responses in Allografted Refractory Follicular Histologies.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 868-868 ◽  
Author(s):  
Issa F Khouri ◽  
Robyn Harrell ◽  
Rosamar Valverde ◽  
Martin Korbling ◽  
Taghi Manshouri ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Prognostic Value ◽  
Chronic Gvhd ◽  
Study Entry ◽  
Refractory Disease ◽  
Ibritumomab Tiuxetan

Abstract Abstract 868 Background: Relapse continues to be the primary cause of treatment failure in patients (pts) with NHL undergoing transplantation. We have previously reported the adverse prognostic value of PET+ in autologous transplants (AUTO) and disease refractoriness in pts undertaking a non-myeloablative allogeneic transplantation (NST). In order to improve outcome, we and others have previously established the feasibility of addition of 90YIT to the transplant conditioning. Herein, we report the long-tem efficacy of this strategy in 74 pts. Methods: Each pt received a single dose of 90YIT (0.4 mCi/kg on day -14) with BEAM as a conditioning regimen in AUTO candidates [relapsed chemosensitive diffuse large cell b-cell (DLBCL); relapsed chemosensitive follicular (FL) if no matched sibling donor was available; mantle cell (MCL) in first remission; age ≤ 65], or with fludarabine, cyclophosphamide and rituximab (Blood 2008:111:5530) in candidates for NST (relapsed chemosensitive or refractory FL and MCL, transformed NHL if not candidates for AUTO, CLL, up to 50% marrow involvement with disease, age ≤ 70). Results: This cohort included 40 pts (DLBCL=25, FL=11, MCL=3, SLL =1). Median age was 53 (range, 31-65) years. Median prior treatments was 2 (range,1-4). At transplant, 21(52.5%) were in CR, 16 (40%) in PR, and 3 pts (7.5%) with DLBCL had stable disease. Nine pts (22.5%) had elevated LDH and 7 of 38 (18%) were PET +. At study entry, median serum rituximab level was 5mcg/ML (range, 0-56.4), and soluble CD20 serum level was 457 nM/L (range, 20.7-1501). Adverse events were similar to those with BEAM alone, and 4 pts (10%) developed secondary malignancies. Median time to >ANC 500 was 9 (range, 7-12) days and to platelet >20,000/mm3 was 11 (range, 2-90) days. At a median follow-up time of 3.6 (range,1.4 - 4.9) years, the 3-year overall (OS) and progression-free survival rates (PFS) were 78% and 64%, respectively. We were not able to identify important determinants of outcome; this included PET+, serum rituximab and soluble CD20. Although histology had no statistically significant impact, a persistent pattern of relapse over time was observed in FL (PFS at 1-,2- and 4-year were 91%, 64% and 45%, respectively), whereas a plateau was observed in DLBCL at 24 months (PFS of 76%). This cohort included 34 pts (FL=11, CLL=20, DLBCL=2, MCL=1). Median age was 59 (range, 29-70). Eight of the 11 pts with FL had high [n=6 (55%)] or intermediate [n=2 (18%)] FLIPI at study entry; 8 (73%) were PET+, and 6 (55%) had refractory disease (non-responding or progressing to at least two lines of therapies such as R-CHOP or RICE). Seven pts with CLL (35%) had refractory disease; 10 of 16 (62.5%) had unmutated IgVH, and 5 of 14(36%) had p53 mutation. Peripheral blood from HLA-compatible sibling donors was the source of graft in all pts. Tacrolimus and methotrexate were used for GVHD prophylaxis. Median time to ANC >500 was 11(range, 8-17) days, and to platelets > 20,000/mm3 was 10 (range, 0-55 days). Median donor T cells at days 30 and 90 were 90% and 100%, respectively. Cumulative incidence (CI) of acute II-IV GVHD was 32% (none had grade 3, one had grade IV), and the CI of extensive chronic GVHD was 44%. With a median follow-up time of 22 (range, 3-73) months, the PFS rates at 3-year for FL and CLL were 100% and 37%, respectively. The causes of failure in CLL were progression (n=6) and complications related to chronic GVHD (n=2). Conclusions: These data provide evidence that combining 90YIT at 0.4mCI/kg with the conditioning improves outcomes in NHL pts undergoing AUTO or NST, but not in CLL. Our results also represent the first report showing that the combination may overcome the negative prognostic value of PET+ in NHL, and that the addition of 90YIT to NST conditioning can induce long-term remission in relapsed refractory FL without added toxicity. Verification of our results in a larger cohort of pts is highly warranted. Disclosures: Khouri: BiogenIDEC: Research Funding. Off Label Use: The use of 90Yttrium Ibritumomab Tiuxetan in stem cell transplantation.

scholarly journals Factors Predicting Outcome after Allogeneic Stem Cell Transplantation in Primary Refractory Acute Myeloid Leukemia: A Retrospective Analysis of the Gruppo Italiano Trapianto Di Midollo Osseo (GITMO)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 731-731
Author(s):  
Elisabetta Todisco ◽  
Fabio Ciceri ◽  
Boschini Cristina ◽  
Fabio Giglio ◽  
Andrea Bacigalupo ◽  
...  
Keyword(s):  
Stem Cell ◽  
T Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Myeloid Leukemia ◽  
Cell Depletion ◽  
Unrelated Donor ◽  
T Cell Depletion

Abstract Background The outcome of primary refractory (PRF) acute myeloid leukemia (AML) patients is poor with a minor proportion rescued by allogeneic hematopoietic stem cell transplantation (HSCT). The identification of pre-HSCT variables may help to identify PRF AML most likely to benefit from HSCT. The EBMT group reported factors predicting the outcome of 168 patients with PRF AML receiving an unrelated donor stem cell transplantation; 5-years OS was 22% and factors associated to an improved survival were the numbers of chemotherapy cycles (< 3), bone marrow blast infiltration <38% and patient CMVseropositivity. These clinical findings allowed to define 4 prognostic groups with survival rates ranging between 44% and 0% {Craddock, 2011). We performed a similar analysis focusing on PRF AML patients transplanted in Italy between 1999-2012 with a stem cell graft obtained by a sibling, unrelated donor and cord blood unit. Patients and study design We analyzed the clinical outcome of 242 patients transplanted in 26 GITMO centers. Patients disease status at HCST included PRF AML defined as failure to achieve a complete response (CR) after one or more chemotherapy cycles containing active drugs on AML. The cytogenetic and molecular risk was defined according to the European LeukemiaNet. The main clinical and outcome follow up data were retrieved from the GITMO database. The main end-points of the study were overall survival (OS) and leukemia-free survival (LFS). Results The median age at HSCT was 49 years (18-72) and 55% of patients were male. Before HSCT, 58% received ≤ 2 chemotherapy cycles. Median time from diagnosis to HSCT was 6 months (1-19) and in 85% was ≥ 3 months. An intermediate-II/adverse karyotype was detected in 58% of patients, > 25% marrow blast infiltration or any level of peripheral blood (PB) blasts was found in 60% and a pre-HSCT Karnofsky score < 90 was present in 43%. Donors were HLA identical sibling in 48% and matched unrelated in 19%, related mismatched in 19%, unrelated mismatched in 3% and cord blood in 11%. Anti-CMV antibodies were present in 87% of patients and in 65% of the donors. Conditioning regimen intensity was myeloablative or reduced in 69% and 31%, respectively; 49% of patients received T cell depletion (92% in vivo and 8% ex vivo). Neutrophils and platelets engraftment was achieved in 87% of patients after a median of 17 (9-52) and 17 (3-150) days, respectively. In all, 35 (14%) patients died within 30 days from HSCT. Of 207 patients evaluable for response, 138 (66%) achieved CR after a median time of 32 days (range 16-130) from HSCT and 69 did not (33%). Median survival of patient who achieved CR was 10 months while it was 2 months for those who did not. Seventy patients (51%) relapsed after a median time of 3 months (1-31), 64 died of disease, 6 survived and 2 of these latter reachieved CR. Sixty-eight patients (49%) maintained CR, 34(50%) died and 34 survived. A t the last follow up 42 patients were alive, 36 in CR and 6 with disease with a median follow up of 27 months (range 1,8-14). The median OS of the whole patient cohort was 5,7 months. At 3-years, the OS and LFS was 15% and 23% respectively. AGvHD was registered in 39% of patients (grade > 2 in 30% of cases) while cGVHD occurred in 29% (extended in 44% of cases). The 3-years cumulative incidence of NRM was 17%. By univariate analysis, the number of chemotherapy cycles to achieve CR (≤ 2), the time to HSCT (< 3 months), the cytogenetics risk favorable/intermediate I, the number of marrow blasts < 25% or the absence of blasts in the peripheral blood, the PS ≥ 90 and the lack of any form of T cell depletion, were all associated to a better survival. By multivariate analysis, the number of chemotherapy cycles, (Hazard Ratio (HR): 1.51; 95% confidence interval (CI): 1.04–2.19; P=0.029), the lack of T cell depletion (HR: 1.66; 95% CI: 1.15–2.40; P=0.007), the degree of BM or PB blast infiltration (HR: 1.59; 95% CI: 1.01–2.25; P=0.043), and the PS (HR: 1.46; 95% CI: 1.00–2.14; P=0.048) remained significantly associated with survival. On the basis of this multivariate analysis, we set up a new score predicting a different 3 years OS: score 0 (0 or 1 adverse prognostic factor, with 28% survival), score 1 (2 adverse prognostic factor, 17% survival); score 2 (2 or 3 adverse prognostic factors, 10% survival) (Figure 1) Conclusion The clinical outcome of PRF AML remains poor. The new simple clinical GITMO score helps indentifying patients most likely will benefit or not from the HSCT. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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