High Dose Cyclophosphamide (HD CY) without Hematopoietic Stem Cell Transplantation (HSCT) in Refractory Severe Autoimmune Diseases: 11 Year Experience in Over 100 Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3412-3412
Author(s):  
Amy E. DeZern ◽  
Michelle Petri ◽  
Douglas Kerr ◽  
Daniel Drachman ◽  
Adam Kaplin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Autoimmune Diseases ◽  
Disease Activity ◽  
Median Time ◽  
Neutrophil Count ◽  
Median Number ◽  
High Dose ◽  
Durable Response ◽  
Hematopoietic Stem

Abstract Abstract 3412 Poster Board III-300 Introduction High-dose cyclophosphamide (HD CY) is a potent immunosuppressive agent that is used as conditioning for HSCT in most patients with both hematologic malignancies and autoimmune diseases. HD CY is highly toxic to lymphocytes, but spares hematopoietic stem cells because of their abundant levels of aldehyde dehydrogenase (the primary mechanism of CY inactivation). We and others have shown that HD CY without stem cell support can induce durable remissions in a variety of severe autoimmune diseases. Here, we report the long term follow-up of 124 patients with a variety of severe autoimmune diseases treated with HD CY. Methods From August 1996 through August 2008, 124 consecutive patients with severe, refractory autoimmune diseases (excluding acquired severe aplastic anemia) were treated with HD CY (50mg/kg/d) for 4 consecutive days without HSCT. Six days after the last dose of CY, all patients received granulocyte colony stimulating factor (5 μg/kg/day) until the neutrophil count exceeded 0.5 × 109/liter. Response was defined as a decrease in disease activity in conjunction with a decrease or elimination of immune modulating drugs. Relapse was defined as worsening disease activity and/or a requirement of an increase in dose or administration of a new immunosuppressive medication. Results The most common diseases treated with HD CY included lupus (n=42), multiple sclerosis (MS, n=32), myasthenia gravis (n=14) scleroderma (SSC, n=10), autoimmune hemolytic anemia (n=9) and pemphigus (n=9). The median follow up is 47 (range 1-127) months. All patients experienced rapid hematopoietic recovery: an absolute neutrophil count (ANC) > 500/μL was achieved at a median of 13 (range 8-22) days after the last dose CY and the median duration of an ANC < 500/μL was 9 (range 4-23) days. The median time to last platelet transfusion after completion of CY was 13 (range 0-33) days and the median time to last packed red blood cell transfusion was 12 (range 0-24) days. The median number of PRBC transfusions was 2 (range 0-27) and the median number of platelet transfusions was 2 (range 0-18.) The overall treatment related mortality was 0.8% with the lone death occurring in a non-neutropenic SSC patient on day 51 after HD CY. Median number of hospitalized days was 4 (range 0-55) days. The overall response rate was 94% with 42% of responders maintaining a durable response at the time of analysis. Durability of response seemed to vary according to the underlying disease and/or disease severity. The actuarial event-free survival (EFS) at 60 months is 10.6% for SLE, 31% for MS, 42.1% for MG, 50% for AIHA, 33% for pemphigus, and 25% for the other diseases. Interestingly, disease activity improved from pre-HD CY in virtually all patients even at the time of relapse, as many patients became responsive to immunosuppressive agents that were previously ineffective in controlling their disease. Discussion HD CY with or without HSCT has a potent disease modifying effect in wide variety of autoimmune disorders. These data suggest that eliminating HSCT after HD CY maintains both its efficacy and safety. The duration of cytopenias compares favorably with HSCT, especially when factoring in the mobilization phase of HSCT. Furthermore, eliminating mobilization and HSCT may have at least theoretical advantages in that the overall duration of the procedure is shortened, any toxicity associated with mobilization is avoided, and the potential of reinfusing autoreactive lymphocytes with the autograft is averted. Disclosures Jones: Accentia: Patents & Royalties. Brodsky:Accentia: Patents & Royalties.

Evaluation of Safety and Efficacy of Different Stem Cell Mobilization Regimens in 110 Patients with Light Chain Amyloidosis

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 3709-3709 ◽  
Author(s):  
Marion Hansberg ◽  
Stefan O Schoenland ◽  
Anja Mangatter ◽  
Sascha Dietrich ◽  
Peter Dreger ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Light Chain ◽  
Median Number ◽  
Lower Amount ◽  
Hematological Toxicity ◽  
High Dose ◽  
Al Amyloidosis ◽  
Hematopoietic Stem ◽  
Cd34 Cells

Abstract Introduction: High-dose melphalan (HDM) with autologous hematopoietic stem cell transplantation (SCT) is an effective treatment for patients (pts) with systemic light chain (AL) amyloidosis. Most centers use granulocyte colony-stimulating factor (G-CSF) alone for mobilization of peripheral blood stem cells. The application of mobilization chemotherapy (MC) together with G-CSF might have some advantages, e.g. a higher amount of collected SC and the reduction of the plasma cell load prior to HDM therapy. We have retrospectively analyzed all pts with AL amyloidosis admitted to our centre who received SC mobilization until 2007. Patients and methods: 110 pts received mobilization therapy. Median age was 56 years (range, 35–69 years). Major eligibility criteria were cardiac disease < NYHA stage III and performance status (PS) < 3. Prior to mobilization, 55 pts (50%) had been pre-treated with induction chemotherapy, including 19 pts who had received melphalan. MC was performed with a combination of cyclophosphamide (1g/m2)/adriamycin (60 mg/m2)/dexamethasone (160 mg) (CAD) in 82 pts. The remaining pts received ifosfamide (12 g/m2, Ifo, n=14) or other chemotherapies (n=7). G-CSF (5 ug/kg/day) was started on day 8 after start of MC. Mobilization with G-CSF alone (10 ug/kg/day) was performed in 11 pts (patientxs choice, pts after cardiac transplant). Patients were retrospectively analyzed regarding toxicity and efficacy of SC mobilization as well as hematological reconstitution after HDM. Results: No patient died during mobilization therapy and leukapheresis (LP). Median NCI grade of non-hematological toxicity was 2 and significantly depended of advanced age, lower Karnofsky performance scale and application of Ifo (p<0.05, Table 1). After CAD cardiac toxicity > NCI grade 3 was observed in 3 pts. Main problems of HD-ifo were worsening of kidney function in 8 pts and occurrence of encephalopathy in 7 pts. Due to AL amyloidosis progression 3 pts could not proceed to SC collection and further 5 pts with successful SC collection were not transplanted, respectively. SC mobilization was successful (> 2 × 106 CD34+/kg body weight (BW)) in 105 pts (95%), 4 pts had to be mobilized twice. The median number of collected SC was 8 × 106 CD34+/kg BW (range, 0–46) with a median LP of 1. Previous melphalan treatment and G-SCF mobilization alone were significantly associated with a reduced number of collected SC (p<0.01, Table 1). HDM with SCT was performed in 100 pts with a transplant-related mortality of 3%. Hematological reconstitution was regular: median time to ANC > 1.0/nl 13 days (range, 9–27 days), median time to platelets > 20/nl 11 days (range, 8–102 days). Of note, only one patient received G-CSF post SCT. There was a trend for faster leukocyte recovery for pts receiving more than 6,5 × 106 CD34+ cells/kg BW compared to < 3 × 106 CD34+ cells/kg BW (12 vs. 14 days, p=0.1). One year after SCT 13 pts (16% of evaluable pts) had a reduced platelet count (<150/nl) with a minimum value of 54/nl. This was associated with a lower amount of transplanted SC (p<0.05). Our results differ from those published by Gertz et al., Am J Med, 2002 regarding number of LP (median 2.5) and time to platelet engraftment (14 days). Conclusion: Our analysis shows that MC with CAD is safe and very effective in pts with AL amyloidosis. More than 95% of the CAD pts could proceed to HDM and had a fast and sustained hematological reconstitution after SCT. Due to the non-hematological toxicity Ifo administration can not be recommended. Mobilization with G-CSF alone is also effective and safe but results in lower amount of collected SC. MC with CAD as part of an intensive therapy approach including IC with new agents should be further evaluated in clinical trials. Mobilization therapy (number of pts) Median number of LP Median number of CD34+ cells/kg BW collected Median NCI grade of nonhematological toxicity G-CSF (n=11) 1 (1–2) 5 (0–11) 0 (0–3) CAD (n=82) 1 (1–5) 9 (0–37) 2 (0–4) Ifo (n=14) 1 (1–4) 19 (5–46) 3 (0–3) Mobilization therapy (number of pts) Median number of LP Median number of CD34+ cells/kg BW collected Median NCI grade of non- hematological toxicity G-CSF (n=11) 1 (1–2) 5 (0–11) 0 (0–3) CAD (n=82) 1 (1–5) 9 (0–37) 2 (0–4) Ifo (n=14) 1 (1–4) 19 (5–46) 3 (0–3)

scholarly journals Survival in Patients Who Underwent HLA-Haploidentical Stem Cell Transplantation in Two Centers in Colombia

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 32-32
Author(s):  
Lisbeth Ramirez ◽  
Juan Manuel Herrera ◽  
Angela María Peña ◽  
Maria Luna-Gonzalez ◽  
Claudia Marcela Chalela ◽  
...  
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Retrospective Study ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Median Time ◽  
Clinical Characteristics ◽  
High Dose ◽  
Post Transplantation ◽  
Hematopoietic Stem

Introduction: Allogeneic hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for several malignant and non-malignant hematological diseases. However, sometimes it is challenging to find human leukocyte antigen (HLA)-matched related or unrelated donors, especially in minority populations such as Hispanics. Transplantation of T cell replete HLA haploidentical graft (HaploHCT) followed by a high dose post-transplantation cyclophosphamide (PTCy) to eradicate alloreactive T cells is an option for populations with low donor availability. HaploHCT has emerged as an effective and safe strategy in this population (Luznik L et al. BBMT 2008), but data in Hispanics is scarce. Objective: The aim of our study was to describe the clinical characteristics and assess overall survival at 100 days, 1- and 3-years of patients who underwent haploHCT in two Colombian reference centers. Methods: An observational retrospective study was conducted at two tertiary referral centers in Colombia. Patients who underwent haploHCT at Clinica FOSCAL and Centro Medico Imbanaco between January 2013 and January 2020 were selected. Demographic and clinical characteristics where analyzed using descriptive statistics. The Kaplan-Meier method was used to assess overall survival (OS) rates and the log-rank test was used to compare survival rates between groups. All data were analyzed using R statistical software®. Results: Seventy-six patients were included. Mean age at transplantation was 34 years (range 18-60). Forty-two (57.89%) patients were female. Average body mass index was 19.86kg/m2. The majority of patients (57%) had a pre-transplantation ECOG performance status of 2. The most common indication for haploHCT was acute lymphoblastic leukemia (55.26%), followed by acute myeloid leukemia (23.64%). A sibling was the donor in 69.74% of the cases. Forty-seven (61.84%) patients were ABO-matched group. Peripheral blood stem cells were the graft source in 96% of the patients. The average number of infused CD34+ cells was 11.15 x 106/kg. Fludarabine-melphalan was the most commonly used conditioning regimen (57%), followed by fludarabine-busulfan-thiotepa (39%). Graft-versus-host disease (GVHD) prophylaxis consisted of PTCy (50 mg/kg/day) on days 3 and 4 after HCT and a calcineurin inhibitor plus mycophenolate mofetil from day 5 to day 35 post-HCT. Median time to neutrophil engraftment (neutrophils &gt; 0,5x109/L) was 15 days (range 10-33), while platelet engraftment, defined as as the second day of unsupported platelet count of ≥20 × 109, occurred at a median time of 13 days (range 5-38) post-transplantation. On day 28 post-HSCT, 93.4% of the patients had achieved 100% chimerism. OS was 91% (95%CI 84-97.5) at 100 days, 81% (95%CI 72-90) at 1-year, and 77% (95%CI 68-88) at 3-years after HaploHCT. C onclusion: The results of our haploHCT retrospective study in a Hispanic population are comparable to several other cohorts that have reported similar outcomes of haploHCT compared to HLA-matched HCT. The OS rates reported in our study suggest that haploHCT is a viable option in patients without an HLA-matched related or unrelated donor available, especially in populations with lower rates of suitable donors. Acknowledgements: We deeply thank Gonzalo Gutiérrez García, M.D. for his leadership and guidance implementing the haploHCT program in Clinica FOSCAL. Disclosures Peña: Roche: Honoraria. Salazar:Janssen: Honoraria; Novartis: Honoraria. Sandoval-Sus:MorphoSys US: Consultancy; Janssen: Consultancy; Massive Bio: Consultancy; Celgene: Speakers Bureau. Sossa:Novo: Honoraria; Takeda: Honoraria; Astellas: Honoraria; Roche: Honoraria.

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

Long-Term Follow-Up of Patients Treated with Bortezomib Alone and in Combination with Dexamethasone as Frontline Therapy for Multiple Myeloma.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 796-796 ◽  
Author(s):  
Sundar Jagannath ◽  
Brian G.M. Durie ◽  
Jeffrey Lee Wolf ◽  
Elber S. Camacho ◽  
David Irwin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Survival Rate ◽  
Median Time ◽  
Response Rate ◽  
Sensory Neuropathy ◽  
High Response Rate ◽  
High Dose ◽  
Phase 2 ◽  
Frontline Therapy

Abstract Introduction: Novel therapeutic agents, such as bortezomib (VELCADE®; btz), thalidomide, and lenalidomide, are being used in combination with dexamethasone (dex) as frontline therapies in MM. Phase 2 and 3 trials with limited follow-up have reported a high response rate and feasibility of high-dose therapy and stem cell transplantation (HDT-SCT). Here we present longer follow-up on our phase 2 trial of btz±dex as frontline therapy. Methods: Patients (pts) with measurable disease and KPS ≥50% received btz 1.3mg/m2 on days 1, 4, 8 and 11 of a 3-week cycle for up to 6 cycles. Oral dex 40mg was added on the day of and day after btz for pts achieving &lt; partial response (PR) after 2 cycles or &lt; complete response (CR) after 4 cycles. Responses were assessed using European Group for Blood and Marrow Transplantation criteria, with the addition of near CR (nCR; CR but positive immunofixation). Results: 48 pts were accrued and were evaluable for response; a further 2 registered on the trial declined to proceed. Median age was 60 years, 46% were male, 64% had IgG and 21% IgA, and 50% were Durie-Salmon stage III. At the end of btz±dex treatment, overall response rate (ORR; CR+nCR+PR) was 90% with 19% CR/nCR; an additional 8% achieved a minimal response (MR). Response to btz alone was rapid; response rate by end of cycle 2 was 50%, including 10% CR/nCR. Dex was added for 36 (75%) pts: 17 at cycle 3, 18 at cycle 5, and 1 at cycle 6. Addition of dex improved best responses to btz in 23 (64%) pts, with 12 improving from stable disease to MR or PR, 9 from MR to PR, 1 from PR to nCR, and 1 from nCR to CR. Median time to best response was 1.9 months. For all 48 pts, with a median follow-up of 24 months, median time to alternative therapy (TTAT) was 7 months (range: 2–25; this includes pts who went on to HDT-SCT), and median overall survival (OS) has not been reached; 1-year survival rate was 90%. For pts not proceeding to HDT-SCT, median TTAT was 22 months, median OS has not been reached; 1-year survival rate was 80%. 23/48 pts proceeded to HDT-SCT. Median CD34+ harvest was 12.6 x 106 cells/kg (range: 5.1–40.4 x 106) from a median of 2 collection days (range: 1–8). All pts had complete hematologic recovery; median time to neutrophil (ANC &gt;1000/mm3) and platelet (&gt;100,000/mm3) engraftment was 11 days (range: 8–13) and 17 days (range: 10–98), respectively. In the 23 HDT-SCT pts, median TTAT and OS have not been reached; post-transplant 1-year survival rate was 90%. The most common grade ≥2 adverse events for btz±dex were sensory neuropathy/neuropathic pain (37%), fatigue (20%), constipation (16%), nausea (12%), and neutropenia (12%). Two pts developed grade 4 events (1 neutropenia, 1 thrombocytopenia). Conclusion: Btz±dex is an effective frontline therapy for MM, with an ORR of 90%, including 19% CR/nCR, and OS rate of 80% at 1 year. The treatment is well tolerated and toxicities were manageable and reversible. Addition of dex to btz provides improved responses. TTAT for patients not undergoing HDT-SCT was 22 months. The regimen does not prejudice subsequent HDT-SCT; stem cell harvest and engraftment were successful in all pts proceeding to transplant. Consolidation with HDT-SCT further increases the response rate and durability of response. Btz+dex is being compared to VAD as induction therapy prior to HDT-SCT in a phase 3 study.

Durable Remission with Salvage Autotransplants in Patients with Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1227-1227
Author(s):  
Nina Shah ◽  
Khawaja Fraz Ahmed ◽  
Sofia Qureshi ◽  
Jatin Shah ◽  
Robert Z Orlowski ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Median Time ◽  
Chromosomal Abnormalities ◽  
Retrospective Chart Review ◽  
Progression Free Survival ◽  
High Dose ◽  
Hematopoietic Stem ◽  
Remission Duration

Abstract Abstract 1227 Poster Board I-249 Background In comparison with single autologous hematopoietic stem cell transplantation (auto HCT), tandem autologous HCT has resulted in longer event-free and overall survival in randomized trials for patients with newly diagnosed multiple myeloma (MM). Most myeloma patients, however, only receive a single auto HCT. Many of these patients are eligible for a second auto HCT as salvage at the time of relapse. We evaluated the outcome of salvage auto HCT for MM patients treated at our institution. Methods We performed a retrospective chart review and identified 62 MM patients (38 males, 24 females) who received a second auto HCT as salvage between 1/3/1992 and 11/4/2008.. Preparative regimen was high-dose melphalan alone or in combination with other chemotherapy agents, including busulfan, topotecan and bortezomib. Three patients received a combination of thiotepa, busulfan and cyclophosphamide. Results Median interval between the first and salvage auto HCT was 21 months (range 2-81). Median age at salvage HCT was 55 years (37-73) and median prior treatment regimens were 4 (range 2-16). Twelve patients had chromosomal abnormalities on conventional cytogenetic studies. Patients received a median CD34 cell dose of 4 ×106 / kg (range 2.3-11.2). Fourteen patients (22%) experienced grade 3 or higher toxicity after the salvage auto HCT. Two patients died within 100 days with a TRM of 3%. Median time to neutrophil engraftment was 10 days (8-38). Responses after salvage auto HCT were as follows: CR+ near CR 15%, PR 48%, with an overall response rate of 63%. Twenty-seven (44%) patients received post auto HCT maintenance therapy. Median follow-up from salvage HCT was 25 months. Kaplan-Meier estimates of median progression-free survival and overall survival (OS) were 15.5 and 43.3 months, respectively. Median time to progression after the first and salvage auto HCT was 20 and 12 months, respectively, with total remission duration of 32 months from two HCTs. Median OS from the time of diagnosis was 72 months, comparable to reported results with tandem auto HCT. At last follow up, 20 patients were alive and in remission. Conclusions In selected MM patients a second auto HCT for salvage therapy is well tolerated with acceptable toxicity. The combined remission duration and overall survival are comparable to outcomes with tandem autotransplants. Disclosures Qazilbash: Cephalon: Speakers Bureau.

Outcome of IgD Myeloma After Autologous Hematopoietic Stem Cell Transplantation.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4354-4354
Author(s):  
Sofia Qureshi ◽  
Manish Sharma ◽  
Chitra Hosing ◽  
Floralyn L Mendoza ◽  
Jatin Shah ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Renal Insufficiency ◽  
Stem Cell Transplantation ◽  
Median Time ◽  
Partial Remission ◽  
Progressive Disease ◽  
High Dose ◽  
Hematopoietic Stem ◽  
High Dose Melphalan

Abstract Abstract 4354 BACKGROUND Multiple Myeloma (MM) is a clonal disorder of plasma cells characterized by monoclonal immunoglobulin (Ig) secretion. Immunoglobulin D (IgD) MM constitutes <2% of all myeloma cases and is characterized by a younger age, male predominance, frequent extra osseous disease, amyloidosis, renal insufficiency and a poor prognosis. We retrospectively analyzed the outcome of patients with IgD myeloma transplanted at our institution. METHODS Between August 1988 and June 2008, 15 patients with IgD MM (13 males, 2 females) received autologous hematopoietic stem cell transplantation (auto HCT) at MD Anderson Cancer Center. Twelve patients received high-dose melphalan (200 mg/m2) as preparative regimen; 3 patients received high-dose melphalan in combination with other agents. RESULTS At diagnosis 7/15 (47%) patients had Durie-Salmon stage III disease, 6/15 (40%) had serum creatinine ≥2 mg/dl and 6/15 (40%) had hypercalcemia. Median age at the time of auto HCT was 53 yrs (range 38–64 yrs) and median interval between diagnosis and auto HCT was 12.6 months (range 3-75 months). Prior to auto HCT 11 patients achieved a partial remission (PR), one had a very good partial remission (VGPR), 2 had minimal response (MR) and one patient had no response to induction. Median follow-up in surviving patients was 25 months. Median time to neutrophil engraftment (ANC > 500/dl) was 10 days (range 9–15 days) and for platelet engraftment (>20,000/dl) was 11 days (range 8–16 days). Non-relapse mortality at 100 days was 0%. Complete responses were seen in 6/15 (40%) patients; 3 converted from PR to CR, 2 from MR to CR and one from VGPR to CR. Only one patient progressed within 3 months of auto HCT. Kaplan-Meiers estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 38% and 64%, respectively. Median time to progression was 18 months. One patient with complex cytogenetics including deletion 13q had disease progression 7 months following an auto HCT. He subsequently received an allogeneic transplant, achieved stable disease status and died 11 months later due to progressive disease. Another patient received a second auto HCT for relapse, but died 3 months later due to progressive disease. CONCLUSIONS Patients with IgD MM, despite a higher incidence of renal insufficiency and hypercalcemia at diagnosis, can safely receive auto HCT, with overall response rates, PFS and OS comparable to other MM subtypes. Disclosures: Shah: Celgene, Amgen, Novartis, Elan: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Hematopoietic Stem Cell Transplantation for Severe Aplastic Anemia Using Alemtuzumab and Cyclophosphamide as Conditioning Regimen.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3198-3198
Author(s):  
Fernanda Lodi ◽  
Gustavo Teixeira ◽  
Antonio Vaz Macedo ◽  
Rosana Lamego ◽  
Simone Silva Magalhaes ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Aplastic Anemia ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Median Number ◽  
Off Label Use ◽  
Hematopoietic Stem ◽  
Off Label

Abstract Abstract 3198 Poster Board III-135 Introduction Cyclophosphamide (Cy) with/without antithymocyte globulin (ATG) as conditioning regimen for allogeneic hematopoietic stem cell transplantation (AlloHSCT) is the treatment of choice for young patients with severe aplastic anemia (SAA). In developing countries, and particularly in Brazil, ATG costs limit its use in AlloHSCT for SAA patients. Alternative low-cost regiments, like busulfan (BU) with Cy as conditioning regimen is still associated with a significant rate of rejection, especially in heavily transfused patients, and long-term infertility. Alemtuzumab (Cam) was reported as an alternative to ATG for SAA patients, with similar activity and a lower cost. Material and Methods In order to study the effect of the combination of Cy and Cam, we reviewed all AlloHSCT performed for SAA using this conditioning regimen. Between April 2007 and Mai 2009, fifteen patients with SAA (defined by Camitta criteria) underwent an AlloHSCT in our institution. Median age at transplantation was 25 (range 5-42) years. All but one patient had positive CMV serology. Median number of transfusions was 20 (range 10-67). One patient received a second AlloHSCT due to a late (> 4 years) graft rejection. Patients received an unmanipulated bone marrow (n=11) or peripheral blood (n=4) graft as stem cell source and all but one patient were transplanted with an HLA-identical sibling. Median number of nucleated cell infused was 2.86 (range 1.65-6.50)x10 8/kg. Cyclosporin alone (n=10) or in combination with methotrexate (n=5) was used as GVHD prophylaxis. Results Thirteen out of 15 patients presented neutrophil recovery with a median time to > 0.5×10 9 neutrophil/L of 23 (range 13-30) days. Platelet recovery (> 20×10 9 platelets/L) occurred in thirteen patients with a median time of 16.5 (range 9-45) days. Acute graft versus host disease (GVHD) was observed in just one patient (grade II). None of 12 patients alive 100-days after AlloHSCT presented chronic GVHD. Seven patients presented CMV reactivation. One patient did not engrafted and other presented a late (14 months) rejection. One patient became pregnant after alloHSCT and gave birth to a healthy child. With a median follow-up of 315(range 4-782) days, two patients died and the estimate 1-year overall survival rate is 87%. One patient died due to complications of a CNS bleeding that occurred hours before marrow infusion and the other of GI infection while still on neutropenia. Conclusion Use of cyclophosphamide and alemtuzumab as conditioning regimen is a valid option in SAA patients undertaking AlloHSCT, with significant lower rates of acute and chronic GVHD. Nevertheless, a longer follow-up is required to properly evaluate rejection incidence. Disclosures Off Label Use: Drug: Alemtuzumab Off-label Use: Aplastic Anemia.

Phase II Prospective Multicenter Study of Treosulfan Based Reduced Intensity Conditioning In Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies From 10/10 HLA Identical Unrelated Donor

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2353-2353 ◽  
Author(s):  
Mauricette Michallet ◽  
Mohamad Sobh ◽  
Stephane Morisset ◽  
Nathalie Tedone ◽  
Jacques-Olivier Bay ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Cumulative Incidence ◽  
Unrelated Donor ◽  
Reduced Intensity Conditioning ◽  
Hematopoietic Stem ◽  
Cd34 Cells ◽  
Grade Ii ◽  
Reduced Intensity

Abstract Abstract 2353 Background: The key point in allogeneic hematopoietic stem cell transplantation (allo-HSCT) is to find the optimal balance between the graft-versus-host disease (GVHD) and the graft-versus-leukemia (GVL) effect particularly in the unrelated HSCT settings, without forgetting the important role of conditioning. Objective: To evaluate the toxicity and efficacy of a new reduced intensity conditioning regimen including Treosulfan, followed by allo-HSCT from a 10/10 HLA identical unrelated donor. Materials and Methods: This prospective study included adult patients presenting a hematological malignancy in need of allo-HSCT using a 10/10 HLA identical unrelated donor. Accepted diagnoses were: CML in 1st chronic phase (CP) resistant to imatinib, in 2nd CP or in complete remission (CR) after blast crisis. Multiple myeloma (MM) or chronic lymphocytic leukemia (CLL) in stage B or C in response after relapse post-auto-HSCT. Acute lymphocytic or myeloid leukemia (ALL, AML) patients in CR1 at high risk or <CR1. Myelodysplasic syndrome (MDS) with poor prognostic factors. The conditioning included: Treosulfan 12g/m2/day intra-venous (day-6 to day-4), fludarabine 30mg/m2/day intra-venous (day-6 to day -2) and ATG 2.5 mg/kg/day (day-2 to day-1). GVHD prophylaxis used cyclosporine A oral (5mg/kg/day) or iv. (3mg/kg/day) from day-1. Peripheral stem cells after mobilization by G-CSF were used as HSC source. Results: Between February 2005 and July 2009, 56 patients were included in 5 different French centers, 30 (54%) males and 26 females with a median age of 57 years (18-65.5). There were 38 (68%) myeloproliferative disorders [29 AML (14 in CR1, 14 CR2 & 1<CR), 8 MDS (1CR1 and 7<CR) and 1 CML in CR1] and 18 (32%) lymphoprolifative disorders [9 MM in PR, 6 CLL (2CR1 & 4PR) and 3 ALL(1CR1 & 2CR2)]. Among 45 explored for cytogenetics, 23 (51%) were normal and 22 with poor prognostic. Before transplantation, two patients did not receive any previous treatment, 21 received 1 line, 22 two lines and 11 > 2 lines. For sex-matching, 49% of patients were sex-mismatched (half of them were F>M). For CMV, 43% were -/-, 25% +/+, 28% +/&minus; and 1% -/+. For ABO matching, 52% were compatible, 24% major incomp. & 24% minor incopm. The median time between diagnosis and allograft was 15 months (4-168). The median number of infused CD34+ cells was 6.5 × 106/Kg(1-17.2) Fifty-four (96%) patients engrafted with a median time to neutrophils (>0.5G/l), and platelets (>50G/l) recovery of 16 days (4-86), 11 (4-82) respectively. Seventeen patients developed aGVHD grade ≥II (8 grade II, 2 grade III & 7 grade IV) with a cumulative incidence at 3 months of 31% (25-38). The cumulative incidence of cGVHD was, at 12 months: 32% (25-39) limited and 6% (2-10) extensive; at 18 months: 34% (27-47) limited and 8% (5-12) extensive. After a median follow-up of 13 months (1-57), the median overall survival (OS) was not reached with a 3 years probability of 52% (38-71). The median time of event free survival (EFS) was 15 months (8 - 57) with a 3-years probability of 47% (35-64). The cumulative incidence of relapse at 3 years was 25% (19-31) and the cumulative incidence of transplant-related mortality (TRM) at 12, 18 and 36 months was 20% (16-27), 23% (16-29) (same at 18 & 36 months) respectively. At the last follow-up, 22 patients died, 7 due to relapse and 15 due to TRM (5 pneumonia, 4 GVHD, 1 secondary malignancy and 6 other causes). We showed in a univariate analysis a higher 3-years OS of patients in CR1 (65%) compared to those <CR1 (44%) at transplantation with a significant better benefit for AML patients (76%). Patients with active cGVHD seem to benefit for the GVL effect on OS with a high significant difference (HR=0.2 (0.1-0.6) p=0.002). The multivariate analysis studying age, sex matching, ABO compatibility, CMV matching, type of disease, CD34+ cells number, cytogenetics, number of previous treatments, disease status and interval diagnosis-allo-HSCT showed: a negative significant impact of both minor ABO incompatibility (p<0.001) and CMV+/&minus; (p=0.01) on OS, a negative significant impact of patients <CR (p=0.03) on relapse. There was no impact of studied factors on TRM. Conclusion: We showed very promising results in terms of OS, relapse and TRM with an impressive GVL effect, in heavily pre-treated patients and transplanted using unrelated donors. Treosulfan appears to be a good choice for conditioning especially with a better outcome in AML patients in CR1. Disclosures: No relevant conflicts of interest to declare.

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