Patients with Immunoglobulin Light Chain Amyloidosis (AL) Undergoing High Dose Chemotherapy with Autologous Stem Cell Transplantation (ASCT) have Superior Outcomes As Compared to Patients with Multiple Myeloma (MM)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 600-600
Author(s):  
Kirupananthan Seenithamby ◽  
Angela Dispenzieri ◽  
Martha Q Lacy ◽  
Shaji K. Kumar ◽  
Francis K Buadi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Plasma Cell ◽  
Conditioning Regimen ◽  
Complete Response ◽  
High Dose ◽  
Data Set ◽  
Risk Of Death ◽  
Hematologic Response ◽  
Significant Difference ◽  
Disease Specific

Abstract Abstract 600 Background: Both MM and AL are plasma cell neoplasms. The underlying clone in both diseases appears to be different not only in terms of “tumor burden” but also in terms of their underlying biology. The overall “fitness” of patients with these two diseases is also different, with AL patients having more major organ dysfunction. Therapy for both diseases is directed at killing the underlying clone. ASCT is one method of reducing the clone size and thereby improving overall survival. Post-ASCT outcomes between the two diseases have never been formally compared. Methods: We compiled all patients with a diagnosis of AL or MM who received ASCT at the Mayo Clinic Rochester between June 1996 and January 2011 to compare outcomes. Patients were retrieved from two prospectively maintained clinical transplant data bases (M.A.G.). Differences between groups were compared using Fisher's exact and Wilcoxon tests. Survival was calculated using the method of Kaplan-Meier, and differences between survival outcomes were calculated by log rank. Cox regression modeling was done to determine how non-disease specific variables—i.e. age, time period of ASCT, number of prior regimens, time to ASCT from diagnosis and acquisition of complete response (CR)—affected outcomes. All statistical analyses were performed using JMP (SAS, NC) software. This study was approved by the Mayo IRB. Results: The data set was comprised of 454 patients with AL and 1116 patients with MM. There were significant differences between the two respective groups of patients in terms of number of prior regimens (0 vs 1, p<0.0001), time to ASCT (3.95 months vs 7.20 months, p<0.0001), intensity of conditioning regimen (non-attenuated in 69.4% vs 89.1%, p<0.0001), serum creatinine (1.1mg/dl vs 1mg/dl p<0.0001), creatinine clearance (72.5 ml/minute vs 80 ml/minute p<0.0001), albumin (2.61g/dl vs 3.50g/dl, p<0.0001) CRP (0.40mg/dl vs 0.63mg/dl p<0.0001), LDH (196 U/l vs 182U/l, p<0.0001), and bone marrow plasmacytosis at transplant (6% vs 9%, p<0.0001). Hematologic response rates were also significantly different between the groups, with higher overall hematologic response in the MM group (90.9% vs 79.5%, p<0.0001) and higher complete response (CR) rates (40.1% vs 29.4%, p<0.0001) in the AL group. With a median follow-up of surviving patients of 68 months, the respective median overall survival (OS) for the AL and MM patients was 113 and 59.5 months, p<0.0001. Notably, the 5-year OS of AL and MM patients achieving CR were 91.4% and 57.7%, respectively, p<0.0001. If only those patients who were transplanted within 1 year of their diagnosis are included in the analysis, the respective 5-year OS of AL and MM patients achieving CR were 90.4% and 61.3%, p<0.0001 (Figure 1). To correct for imbalances in non-disease specific parameters, 3 multivariate analyses were performed using: 1) all patients; 2) only those achieving CR; and 3) only those who achieved a CR and were transplanted within 12 months of their diagnosis (Table 1). Among those patients achieving CR, MM patients had nearly a 4-fold risk of death as compared to patients with AL. Conclusion: Although ASCT is not available to all patients with either AL or MM, there is a significant difference in outcomes based on the diagnosis. Patients with AL who undergo ASCT enjoy a superior survival as compared MM patients undergoing the same procedure. This difference is most notable among those patients who achieve CR suggesting very different plasma cell biology between the two diseases. Disclosures: No relevant conflicts of interest to declare.

Primary Plasma Cell Leukaemia and Autologous Stem Cell Transplantation.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 731-731
Author(s):  
Mary B. Drake ◽  
Simona Iacobelli ◽  
Anja van Biezen ◽  
Jane F. Apperley ◽  
Dietger W. Niederwieser ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Plasma Cell ◽  
Autologous Transplantation ◽  
Cell Leukaemia ◽  
Rank Test ◽  
Tumour Mass ◽  
Data Set ◽  
Significant Difference ◽  
Plasma Cell Leukaemia

Abstract Introduction: Primary plasma cell leukaemia (PCL) is a rare disorder representing less than 5% of malignant plasma cell disease and is associated with a poor prognosis with median survivals in PCL reported at 8 to 12 months, significantly shorter than for Multiple Myeloma even when the comparison is adjusted to compare only with Multiple Myeloma of high tumour mass. Treatment of PCL with alkylating agent-based therapy is ineffective and while polychemotherapy may offer improved survival, results remain disappointing with a few exceptions. Autologous transplantation is now being used widely in the treatment of these patients and this report summarises the European Blood and Marrow Transplant (EBMT) experience of this disorder. Patients and Methods: A retrospective study was carried out with 20844 patients with common type multiple myeloma (58% IgG, 21% IgA and 19% light chain types only) and 272 patients with primary plasma cell leukaemia who underwent first autologous transplantation between 1980 and 2006. All patients were reported to the EBMT registry using MED-A (limited data set) or MED-B (more extensive data set) forms. All autografted patients were included in the study regardless of the availability of complete MED-A or MED-B data. The proportion of patients that could be evaluated for each parameter was noted and the number of evaluable patients included in the result. Comparisons between the two groups were made using Chi-squared test for categorical data and the Mann-Whitney test for continuous data. Overall Survival and Progression-Free Survival were calculated using the Kaplan-Meier method and comparisons were made using the Log-Rank test. Relapse/Progression and Death without relapse or progression probabilities were computed by the proper non-parametric estimator for outcomes with competing risks and compared by the Gray test. Results: There were no significant differences in age and gender of the PCL and myeloma groups. Calcium and albumin were also not significantly different, however, haemoglobin was significantly lower in the PCL group (11g/dl versus 9g/dl - P=0.000) while creatinine was significantly higher in the PCL group - 92 micro mol/l versus 122 micro mol/l - P=0.000). B2 microglobulin was significantly higher in the PCL group which tends to be diagnosed with a more advanced disease. There was no difference in the type of graft used or in the use of total body irradiation but the PCL group were transplanted within a shorter time from diagnosis (6.0 v 7.7 months - P=0.000). While there was no significant difference in engraftment, PCL patients were more likely than myeloma patients to enter CR post-autologous transplantation. Despite this, overall survival for the PCL patients was greatly inferior to the myeloma patients - 62.3 months (CI 60.4–64.3) versus 25.7 months (CI 19.5–31.9 - P=0.000). Poor survival is accounted for by an increase in relapse-related mortality and post-transplant responses of short duration. Conclusion: This is the largest study of plasma cell leukaemia patients ever reported. Our data shows an improved outcome for these patients with use of autologous transplantation but undoubtedly this transplant group represents the fittest of such patients and their outcome is still greatly inferior to comparable myeloma patients.

Comparison of Early and Late Autologous Stem Cell Transplants for Multiple Myeloma: A Single Institution Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 928-928
Author(s):  
Shaji Kumar ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Suzanne R. Hayman ◽  
S. Vincent Rajkumar ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Overall Survival ◽  
Stem Cell ◽  
Plasma Cell ◽  
Complete Response ◽  
High Dose ◽  
Cell Transplant ◽  
Plateau Phase ◽  
Overall Response ◽  
Delayed Group

Background: High dose chemotherapy and autologous stem cell transplant (SCT) remains the preferred therapy for eligible patients with multiple myeloma (MM). Several studies have demonstrated an improvement in median survival with use of SCT. Patients with myeloma may undergo SCT immediately following 4–6 cycles of ‘induction’ therapy or at the time of relapse from the initial plateau phase. Available evidence does not suggest a survival difference between the two approaches. Methods: We retrospectively evaluated our experience with autologous single SCT for MM to compare the results of delayed SCT to early SCT. We identified from our transplant database, 202 patients with MM, who underwent SCT between October 1992 and November 2002. 101 patients, who responded to induction chemotherapy, had stem cells collected in plateau phase, received maintenance chemotherapy and had SCT at the time of first relapse (delayed SCT group). The remaining 101 patients, after initially achieving a response underwent upfront SCT (early SCT group). Patients refractory to initial therapy were excluded from this study. Most of the early transplants were done in the recent years and hence this group has a shorter follow up. Results: The study cohort had a median age of 55 years (range 29 – 72) at diagnosis consisting of 126 males (62%), with no significant demographic difference between the two groups. As expected measures of tumor burden (M protein, B2M and marrow plasma cell percentage) were significantly higher in the delayed group. Plasma cell labeling indices and presence of abnormal cytogenetics were higher in the delayed SCT group as well at transplant. TBI containing regimens were used more often in the delayed group reflecting a difference in the time periods of transplant. There was no difference between the groups in terms of overall response to transplant though complete response rate was higher for the early transplants. (Table). There was no difference in the time to overall response between the groups (P=0.13, Kaplan Meier estimate). Though the median progression free survival (PFS) from transplant was shorter for the delyaed SCT group, the overall survival (OS) from diagnosis of MM was comparable for the two groups (Table). The overall survival estimate at 5 year from diagnosis was 60% for both groups. Conclusions: Review of our experience demonstrates comparable overall survival for an early SCT compared to SCT at the time of relapse. Although there is an advantage for early SCT in terms of more chemosensitive disease as shown by a longer PFS from SCT, there is no benefit in OS from time of diagnosis. Patient preference and other co-morbidities should play a role in the decision regarding timing of transplant. This study has the disadvantage of being retrospective in nature and the two groups being spread over different periods in time. Early (n=101) Delayed (n=101) P Overall Response 100 (99%) 94 (94%) 0.07 Complete Response 43 (42%) 28 (27%) 0.04 Median PFS (From Transplant) 26.7 months 14.8 months <0.0001 Median OS (From diagnosis) 67 months 70 months 0.1

A Comparison of Beam and Yttrium 90 Ibritumomab Tiuxetan (Zevalin®) in Addition to Beam (Z-BEAM) in Older Patients Undergoing Autologous Stem Cell Transplant (ASCT) for B-Cell Lymphomas: Impact of Radioimmunotherapy on Transplant Outcomes.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3043-3043 ◽  
Author(s):  
Amrita Y. Krishnan ◽  
Auayporn Nademanee ◽  
Andrew Raubitschek ◽  
Henry C. Fung ◽  
Arturo Molina ◽  
...  
Keyword(s):  
Overall Survival ◽  
B Cell ◽  
Older Patients ◽  
Cell Lymphoma ◽  
Conditioning Regimen ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Significant Difference

Abstract Background: ASCT is an effective treatment for patients with high risk NHL. However, relapse rates remain high. Attempts at further dose intensification are limited by regimen-related toxicity especially in older patients. Zevalin as a single agent has showed activity in aggressive Non-Hodgkin’s Lymphoma (NHL). We therefore, devised a novel conditioning regimen (Z-BEAM) combining standard dose Zevalin (0.4mci/kg) with high dose BEAM (BCNU 150mg/m2 day-7,-6, cytarabine 800mg/m2 and etoposide 800mg/m2 day-5 to day-2, and melphalan 140mg/m2 day-1). Herein, we provide an update on the study and also retrospectively compare this new conditioning regimen with conventional high dose BEAM in older patients (age >=50). Between 1995 and 2005, 65 patients (BEAM n=32, Z-BEAM n=33) underwent ASCT utilizing these regimens. Patient selection was similar for Z-BEAM and BEAM. Patients received BEAM prior to the opening of the Z-BEAM protocol and similiarly after the Z-BEAM protocol completed accrual. The groups were well matched for most demographics and disease status. Median age: Z-BEAM - 62 yrs (range 50–78), BEAM - 64 yrs (range 50–77); 1st CR/PR pts comprised 45% in the Z-BEAM arm and 34% in the BEAM, > =1st Relapse 42% vs 50% and induction failure 12% vs 15%. (p=0.7). Median number of prior regimens was 3 in the Z-BEAM group vs 2 in the BEAM arm.(p=0.08) 54 % had bulky disease at diagnosis in the Z-BEAM group vs 41% in the BEAM group (p=0.30). Results: Two-year OS was 78% for all pts (95%CI, 67–86). Two-year OS/PFS in the Z-BEAM group was 88%(95% CI, 70–95)/72 %(95% CI, 57–83) respectively vs 65% (95%CI, 48–77)/ 67%( 95CI, 50–79) in the BEAM group (Figure1). Analysis by histology showed that in patients with diffuse large B-cell lymphoma (DLBCL), there was a significant difference in OS/PFS of Z-BEAM vs BEAM, 95% vs 48% at 2 yrs (p=.009)/ 88% vs 48% ( p=0.015). The OS/PFS difference of Z-BEAM vs BEAM in patients with mantle cell lymphoma did not reach significance. The toxicity profile and transplant related mortality was similar in both regimens. Conclusions: Our study suggests that the addition of Zevalin to the BEAM conditioning regimen is feasible and well tolerated in older patients. The favorable outcome of patients treated with Z-BEAM compared with BEAM alone, especially in patients with DLBCL, suggests that prospective study in a randomized trial is warranted. Overall Survival 
 ZBEAM versus BEAM Overall Survival 
 ZBEAM versus BEAM

Bortezomib-Based Induction Therapy Induces Better Responses and Outcomes of Autologous Stem Cell Transplantation in Newly Diagnosed Patients with Multiple Myeloma: The Results of Korean Multiple Myeloma Working Party Retrospective Study, KMM84

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5184-5184 ◽  
Author(s):  
Seok Jin Kim ◽  
Kihyun Kim ◽  
Jae Hoon Lee ◽  
Min Kyoung Kim ◽  
Jae-Yong Kwak ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Induction Therapy ◽  
Conditioning Regimen ◽  
Working Party ◽  
Complete Response ◽  
High Dose ◽  
Significant Difference

Abstract Introduction: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) generally offers improved outcomes compared with conventional chemotherapy in patients with multiple myeloma. The disease status before ASCT such as the achievement of complete response (CR) was also reported as an important prognostic factor in multiple myeloma. Thus, the type and efficacy of induction therapy could affect the treatment outcome of ASCT because these induction chemotherapy regimens are designed to reduce myeloma burden leading to CR before ASCT. A combination chemotherapy regimen, VAD consisting of vincristine, doxorubicin, and dexamethasone is the induction therapy regimen which has been used for a log time. However, many new induction regimens have been used including thalidomide plus dexamethasone, and bortezomib since their efficacy was proven for relapsed or refractory multiple myeloma. However, the efficacy of these new induction therapy regimens and their effects on outcomes of ASCT has rarely been compared to VAD induction therapy. Methods: We performed a retrospective multicenter analysis supported by the Korean Multiple Myeloma Working Party (KMMWP). We have compared the efficacy of induction therapy regimens including VAD chemotherapy, thalidomide-based induction therapy, bortezomib-containing induction therapy, cyclophosphamide-based therapy. We also assessed the effects of these induction therapies on the outcome of ASCT in terms of response, relapse after ASCT, and survival. Results: We analyzed 344 patients who received induction therapy followed by high-dose chemotherapy with single ASCT at 13 hospitals in Korea. Patients who received tandem ASCT or ASCT followed by allogeneic stem cell transplantation were excluded. Their median age at diagnosis was 55 year old (range 20–72). The most common immunophenotype was IgG kappa and lambda (103, and 63 respectively) while 72 patients had light chain disease (kappa 30, lambda 42). 241 patients (70.1%) received VAD chemotherapy as an induction therapy prior to ASCT, and 35 patients (10.2%) received thalidomide-based chemotherapy before ASCT including thalidomide with/without dexamethasone. 46 patients (13.4%) were exposed to bortezomib including bortezomib alone or combined with other agents such as bortezomib, doxorubicin, dexamethasone (PAD). 22 patients (6.4%) received cyclophosphamide-based induction therapy. Age, sex, stage (Durie-Salmon and International staging system), and immunophenotype were balanced among these four groups of patients. Complete response (CR) rate including nCR (near CR) of VAD chemotherapy was 20.3% (49/241). CR rate of bortezomib and thalidomide-based therapy was 43.5% (20/46), and 37.1% (13/35) respectively. Cyclophosphamide-based induction therapy induced 27.2% of CR (6/22). Thus, CR rate of bortezomib-based induction therapy was significantly higher than other regimens (P &lt; 0.05). There was no significant difference in the stem cell harvest and transplantation-related morbidity based on the type of induction therapy. The melphalan-based conditioning regimen was used in all patients, and the dosage of melphalan was from 100mg/m2 to 200mg/m2. There was no difference of conditioning regimen among the four groups. When we assessed the response after ASCT, the results were as follows: VAD group (48 patients with continued CR, 85 patients with induced CR, 55.2% of CR rate), Thalidomide group (20 patients with continued CR, 12 patients with induced CR, 60.0% of CR rate), Bortezomib group (20 patients with continued CR, 12 patients with induced CR, 69.6% of CR rate), and Cyclophosphamide group (5 patients with continued CR, 7 patients with induced CR, 54.5% of CR rate). There was no significant difference in the stem cell harvest and transplantation-related morbidity based on the type of induction therapy. Relapse rate after ASCT was lower in bortezomib group (34.8%) than VAD group (63.1%), cyclophosphamide group (63.6%), and thalidomide group (54.3%). However, there was no significant difference of overall survival among these four groups. Conclusions: Bortezomib-based induction therapy might be more effective for improving CR rate in patients who received single ASCT. A further prospective study should be warranted to confirm whether this augmented response rate with bortezomib-based induction therapy might be translated into survival benefits.

scholarly journals Evaluation of The Effectiveness and Side Effects of Radiotherapy in Patients With Primary Nervous System Lymphoma. A Single Center Experience

2020 ◽  
Vol 7 ◽  
Author(s):  
Timur Koca ◽  
Aylin Fidan Korcum ◽  
Yasemin Şengün ◽  
Melek Gamze Aksu ◽  
Mine Genç
Keyword(s):  
Central Nervous System ◽  
Overall Survival ◽  
Nervous System ◽  
Side Effects ◽  
Disease Free Survival ◽  
Central Nervous System Lymphoma ◽  
Field Size ◽  
High Dose ◽  
Free Survival ◽  
Significant Difference

Aim: In this study, we aimed to evaluate the overall and progression-free survival, the radiotherapy process and the early and late adverse effects in patients who underwent radiotherapy (RT) for primary nervous system lymphoma in our clinic.Method: Between January 2010 and September 2019, 16 patients who received radiotherapy due to primary central nervous system lymphoma in our clinic were examined according to their statistically significant differences in terms of survival and side effects.Results: The median disease-free survival of the patients was 6 months, and the median overall survival was 12.5 months. 18.75% of the patients could not receive chemotherapy but only radiotherapy. Radiotherapy doses were range from 2600 to 5000 cGy. When patients were evaluated in terms of radiotherapy dose, field size and chemotherapy, no statistically significant difference in overall survival was detected. Cognitive disorders were observed as the most common late side effects while the most common acute side effects in patients were headaches.Conclusion: In the treatment of primary central nervous system lymphoma, changes in radiotherapy portals and radiotherapy doses can be predicted in patients who received high-dose methotrexate chemotherapy or not. Furthermore, it has been considered that more comprehensive studies are needed to increase the success of treatment and provide standardization in treatment, especially in patients with elderly and comorbid diseases.

Sarcomatoid Renal Cell Carcinoma: Biologic Behavior, Prognosis, and Response to Combined Surgical Resection and Immunotherapy

1999 ◽  
Vol 17 (2) ◽  
pp. 523-523 ◽  
Author(s):  
Thomas Cangiano ◽  
Joseph Liao ◽  
John Naitoh ◽  
Frederick Dorey ◽  
Robert Figlin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cell Carcinoma ◽  
Surgical Resection ◽  
Median Duration ◽  
Renal Cell ◽  
High Dose ◽  
Risk Of Death

PURPOSE: Sarcomatoid variants of renal cell carcinoma (RCC) are aggressive tumors that respond poorly to immunotherapy. We report the outcomes of 31 patients with sarcomatoid RCC treated with a combination of surgical resection and immunotherapy. PATIENTS AND METHODS: Patients were identified from the database of the University of California Los Angeles Kidney Cancer Program. We retrospectively reviewed the cases of 31 consecutive patients in whom sarcomatoid RCC was diagnosed between 1990 and 1997. Clinical stage, sites of metastasis, pathologic stage, and type of immunotherapy were abstracted from the medical records. The primary end point analyzed was overall survival, and a multivariate analysis was performed to distinguish any factors conferring an improved survivorship. RESULTS: Twenty-six percent of patients were male and 74% were female, and the median age was 59 years (range, 34 to 73 years). Length of follow-up ranged from 2 to 77 months (mean, 21.4 months). Twenty-eight patients (84%) had known metastases at the time of radical nephrectomy (67% had lung metastases and 40% had bone, 21% had liver, 33% had lymphatic, and 15% had brain metastases). Twenty-five patients (81%) received immunotherapy, including low-dose interleukin (IL)-2–based therapy (five patients), tumor-infiltrating lymphocyte–based therapy plus IL-2 (nine patients), high-dose IL-2–based therapy (nine patients), dendritic cell vaccine–based therapy (one patient), and interferon alpha–based therapy alone (one patient). Two patients (6%) achieved complete responses (median duration, 46+ months) and five patients (15%) achieved partial responses (median duration, 36 months). One- and 2-year overall survival rates were 48% and 37%, respectively. Using a multivariate analysis, age, sex, and percentage of sarcomatoid tumor (< or > 50%) did not significantly correlate with survival. Improved survival was found in patients receiving high-dose IL-2 therapy compared with patients treated with surgery alone or any other form of immunotherapy (P = .025). Adjusting for age, sex, and percentage of sarcomatoid tumor, the relative risk of death was 10.4 times higher in patients not receiving high-dose IL-2 therapy. Final pathologic T stage did not correlate significantly with outcome, but node-positive patients had a higher death rate per year of follow-up than did the rest of the population (1.26 v 0.76, Cox regression analysis). CONCLUSION: Surgical resection and high-dose IL-2–based immunotherapy may play a role in the treatment of sarcomatoid RCCs in select patients.

A Experimental Study and Clinical Result of Prophylaxis aGVHD with Humanized Anti-CD25 Monoclonal Antibody in Haploidentical BMT.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1251-1251
Author(s):  
Shu-Quan Ji ◽  
Hui-Ren Chen ◽  
Heng-Xiang Wang ◽  
Hong-Min Yan ◽  
Mei Xue ◽  
...  
Keyword(s):  
Median Time ◽  
Conditioning Regimen ◽  
Control Group ◽  
High Dose ◽  
Marrow Graft ◽  
Hla Antigen ◽  
Hematopoietic Stem ◽  
Gvhd Prophylaxis ◽  
Significant Difference

Abstract Between February 1999 and March 2004, eighty-seven patients with high risk leukemia, age 3–50 (median 19 year), who needed urgent transplant but no HLA-matched or single HLA-antigen mismatched donors available, received unmanipulated HLA haploidentical BMT. The 87 patients were classified as follows AML 27 (CR1 in 7, CR2 in 15 and 5 in relapse), All 38 (CR1 in 4, CR2 in 30 and 4 in relapse) , CML 22 ( 4 in CP, 12 in AP and 6 in BP). All donors were HLA-haploidentical relatives who had at least two major histocompatibility complex antigen mismatched with the recipients. 87 patients underwent haplo-BMT with G-CSF primed BM as stem cells. All patients received a same conditioning regimen including high dose Ara-C, Cyclophosphamide, antithymocyte globulin and total body irradiation to provide both immunosuppression and myeloablation. GVHD prophylaxis consisted of anti-thymocyte globulin, cyclosporin A, methotrexate and mycofenolate mofitel. 72 patients underwent the transplants with the addition of CD25 mAb (Basiliximab Novartis) for GVHD prophylaxis designated as CD25 mAb group. Basiliximab 20mg each by 30min intravenous infusion on 2 hours before transplantion and day 4 after transplantaion. The other 15 patients without Basiliximab for GVHD prophylaxis were as the control group. The two group of patients were comparable in disease status, HLA-disparity and median age of patients. Immunophenotyping, limited dilution assay and colony forming assays were used to measure the effect of Basiliximab on the subsets of lymphocytes, cytotoxic T lymphocyte precursors (CTLp) and hematopoietic cells. All donors were primed with G-CSF at 3-5ug/kg/d for 7 days and the marrow cells were harvested on the eighth day. G-CSF donor priming significantly increased CD34+ and colony forming progenitors in the marrow grafts. More importantly, it significantly reduced lymphocytes and reversed CD4+/CD8+ lymphocyte ratio in the grafts. Both of group who were treated with and without Basiliximab had similar marrow graft contents. All patients established trilineage engraftments.The median time to achieve an absolute neutrophil count 0.5x109/L was 19 days (range, 13 to 24 days). The median time to achieve platelets above 20x109/L was 22 days (range, 16 to 32 days). Between the two groups were no differences in engraftment. Incidence of grades II–IV acute GVHD were 13.9% with GVHD-related deaths 6.9% in Basiliximab group and 33.3% with 20% GVHD-related deaths in control group. There were a significant difference between the anti-CD25 mAb treated Vs non-treated group.Forty-nine patients who survived over 12 months were eligible for the evaluation of cGVHD. 12 patients developed extensive cGVHD, one in control group and eleven in Basiliximab group. 49 were alive in CR during a median follow-up of 30 months (range3–64 months), 42 in Basiliximab group and 7 in control group. Basiliximab significantly decreased alloreactive CTLp by 10–100 fold in limiting dilution assays. It had no effect on hematopoietic stem and progenitor cells as determined by in vitro colony-forming assays.The addition of basiliximab as aGVHD prophylaxis effectively reduced severe lethal aGVHD in haplo-BMT. It is possible to selectively eliminate or reduce the number of alloreactive T cells with anti CD25 antibody, which results in prevention of or a reduction in the severity of GVHD.

Treatment of Steroid-Resistant Acute GvHD with OKT3 and High-Dose Steroids Versus High-Dose Steroids Alone.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 141-141
Author(s):  
Stefan Knop ◽  
Holger Hebart ◽  
Alois Gratwohl ◽  
Ernst Holler ◽  
Jane F. Apperley ◽  
...  
Keyword(s):  
Conditioning Regimen ◽  
Infectious Complications ◽  
Response To Treatment ◽  
High Dose ◽  
Steroid Resistant ◽  
Organ Systems ◽  
Incidence And Mortality ◽  
Significant Difference ◽  
One Year ◽  
Disease Free

Abstract Despite new conditioning regimens and introduction of novel immunosuppressants in hematopoietic cell transplantation (HCT), acute graft-versus-host disease (aGvHD) remains an often life threatening complication. Methylprednisolone (MP) 2 mg/kg body weight (BW) per day is the initial standard treatment with escalation to high-dose MP (10 mg/kg BW per day) for non-responders. Recently, we demonstrated OKT3 muromonab to be an effective second-line and subsequent salvage treatment. Response duration, however, was frequently short-lived in those extensively pretreated patients and inversely correlated with duration from allografting. In the current randomized multicenter trial we investigated high-dose MP (HD-MP) versus OKT3 5 mg per day plus HD-MP. Primary endpoints were response to treatment after 100 days and survival at one year from HCT. Secondary endpoints were side effects and incidence of infectious complications. Patients with resistant °II to IV aGvHD on standard MP following allogeneic HCT were randomized to HD-MP or OKT3 + HD-MP after exclusion of other severe HCT-related complications. Eighty patients from 6 transplant centers were enrolled. Median age for the 40 patients who received OKT3 + HD-MP was 40 (range, 19 – 65) years and for the 40 patients who received HD-MP 39 (range, 19 – 56) years. There was no statistical significant difference between the groups for severity of aGvHD (°II vs. °III/IV); stem cell source (bone marrow vs. peripheral blood progenitor cells); GvHD prophylaxis (CSA vs. ATG+CSA); and conditioning regimen (TBI/Cy vs. Bu-Cy). However, significantly fewer HCTs in the OKT3 + HD-MP group were from HLA-identical siblings. Currently, 62 subjects are evaluable for response. In both arms, reduction of severe and proportional increase of moderately-severe aGvHD was observed with resolution of all °IV cases until day +30. However, significantly more patients in the OKT3 + HD-MP became disease-free (°0) by day +100 when compared to patients treated with HD-MP alone: 39.3 % vs. 20.6 % (p=0.03). In the OKT3 + HD-MP group relative increase of disease-free patients was higher for all organ systems at all time points when compared to patients on HD-MP treatment without reaching statistical. With respect to infectious complications, the incidence of both bacterial and viral infections was slightly and for invasive aspergillosis significantly higher in the HD-MP when compared to the OKT3 + HD-MP group (20.6 vs. 10.7 %; p=0.025). Treatment related mortality was higher in the HD-MP group when compared to the OKT3 + HD-MP group by days +30 (32.3 vs. 10.7 %) and +100 (55. 9 vs. 39.3 %). However, this did not translate into a significantly better one-year survival with the currently evaluable patients: one-year survival for the HD-MP group was 32.4 % and for the OKT3 + HD-MP group 46.4 %. (p=0.72). We conclude that OKT3 + HD-MP results in higher response rates for patients with steroid-resistant aGvHD and thus leads to a better immune reconstitution after HCT what is reflected by reduced incidence and mortality of infectious complications. Final results of the trial will be presented.

Autologous Transplant Event-Free Survival (EFS) Following Failure of CHOP-Rituximab (CHOP-R) for Diffuse Large B-Cell Lymphoma (DLBCL) Is the Same as the EFS Following Failure of CHOP Alone.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 890-890 ◽  
Author(s):  
Julie M. Vose ◽  
Philip J. Bierman ◽  
James C. Lynch ◽  
Gregory Bociek ◽  
James O. Armitage
Keyword(s):  
Overall Survival ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Autologous Stem Cell Transplantation ◽  
Chemotherapy Resistance ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
High Dose

Abstract Several studies have now identified that the addition of rituximab (R) to CHOP chemotherapy has increased the complete response, EFS, and overall survival (OS) for patients with previously untreated DLBCL. However, concerns of increased resistance of DLBCL following failure of CHOP-R and the inability to salvage those patients with high-dose chemotherapy and autologous stem cell transplantation have been raised. In an attempt to address this issue, we evaluated 103 patients with high risk, relapsed, or refractory DLBCL receiving high-dose chemotherapy and autologous stem cell transplantation at our center between 1999 and 2003. Fifty-six (54%) of the patients received CHOP as their initial induction therapy and 47 (46%) received CHOP-R. The patients ranged in age from 20–73 years (median 50). Sixty patients were male and 43 female. Sixty two of the patients were transplanted < 12 months from diagnosis and 41 were transplanted ≥ 12 months from diagnosis. The patients had received a median of 2 prior therapies (range 1–4). The majority (81%) were chemotherapy sensitive at the time of transplantation. The median follow-up of surviving patients is 27 months ( range 3–74). All patients received a BEAM (C) - based regimen [carmustine, etoposide, cytarabine, melphalan or cycylophosphamide] +/− anti-CD20 monoclonal antibodies. There was no difference in the 2-year EFS for patients failing CHOP vs. CHOP-R (60% vs. 68%, p=0.49). In addition, there was no difference in the 2-year overall survival (OS) of patients failing CHOP vs. CHOP-R (72% vs. 68%, p=0.63). In a multivariate analysis, the only factor predicting for an event (relapse or death) post-transplant was having received ≥ 2 prior chemotherapies (Relative Risk (RR) 7.5, p=0.048) and predicting for death from any cause was chemotherapy resistance (RR 2.5, p=0.037) and an increased lactic dehydrogenase at transplant (RR 4.1, p=0.002). The additional use of a monoclonal antibody with the transplant regimen did not significantly impact outcome in this analysis. This study demonstrates that patients with DLBCL failing CHOP-R are able to be salvaged with high-dose chemotherapy and autologous stem cell transplantation and have a similar 2-year EFS and OS as patients being transplanted following CHOP failure.

Long-Term Follow-Up of a Randomized Phase III Multicenter Study Comparing a Standard Versus an Intensified Conditioning Regimen for High-Dose Chemotherapy in Patients with Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 945-945
Author(s):  
Roland Fenk ◽  
Peter Schneider ◽  
Martin Kropff ◽  
Ali-Nuri Huenerlituerkoglu ◽  
Ulrich Steidl ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Stem Cell ◽  
Conditioning Regimen ◽  
High Dose Chemotherapy ◽  
Phase Iii ◽  
Study Endpoint ◽  
Primary Study ◽  
High Dose ◽  
Significant Difference

Abstract High-dose chemotherapy (HDT) improves the outcome of patients with multiple myeloma (MM) in comparison to conventional chemotherapy. Dose-escalating strategies including tandem HDT are currently evaluated to further improve remission rates and survival of patients. Therefore we conducted a randomized multicenter trial to compare an intensified conditioning regimen with the current standard high-dose melphalan. The primary study endpoint was response rate, with overall survival (OS), event-free survival (EFS) and toxicity analysed as secondary endpoints. Between 1997 and 1999 a total of 56 patients with stage II and III disease, who were matched for age (median 56 years), number of previous therapies (median time from diagnosis to transplant 7 months) and different risk factors (beta2-microglobulin, LDH, CRP, cytogentic abnormalities, chemoresistant disease, IgA-subtype, renal impairment), were randomized. All patients received 2 courses of oral idarubicine/dexamethasone and 2 courses of intravenous cyclophosphamide/adriamycine in combination with G-CSF followed by peripheral stem cell collection. Thirty patients were treated with melphalan 200mg/m2 (HD-M) whereas 26 patients received idarubicine 42mg/m2, melphalan 200mg/m2 and cyclophosphamide 120mg/kg (HD-IMC) followed by autologous blood stem cell transplantation. Acute toxicity was higher with HD-IMC, including 5 (20%) treatment-related deaths due to infections versus none (0%) in the HD-M group. This lead to early termination of the study. Severity of mucositis (grade III-IV 19 vs. 8 pts., p=0.001), CRP (20 vs. 7 mg/dl, p<0.001), days of fever (11 vs. 3, p<0.001), days with iv-antibiotics (13 vs. 4, p<0.001), number of erythrocyte-transfusions (6 vs. 2, p<0.001), number of platelet-transfusions (16 vs. 4, p<0.001) and days to granulocyte engraftment (18 vs. 11, p=0.007) were significantly higher after HD-IMC. After a follow-up of 5 years analysis restricted to patients surviving the first 30 days after HDT showed a trend to higher response rates (CR+vgPR: 47% (95%CI 24–72%) vs. 35% (95%CI 18–56%), PR 37% (95%CI 17–63%) vs. 48% (95%CI 29–68%) and time-to-progression (median 31 vs. 15 months, p=0.1) in the HD-IMC treatment arm in comparison to HD-M, but there was no significant difference in EFS and OS (median 22 vs. 30, p= 0.31 and 66 vs. 66 months, p=0.8, respectively). Univariate analysis demonstrated that LDH levels > 200 U/L (p=0.04) and chemoresistant disease (p=0.05) were a bad prognostic factor for EFS. Beta2-Microglobulin levels > 5mg/dl (p=0.01), abnormal conventional cytogenetics (p=0.02) and LDH levels > 200 U/L (p=0.03) were predictive for an inferior OS. In conclusion intensified conditioning for HDT had an intolerable high treatment-related mortality and did not improve EFS and OS in patients with multiple myeloma.

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