High-dose chemotherapy with autologous stem cell transplantation for multiple myeloma: what predicts the outcome? Experience from a developing country

We analyzed the results of 108 patients (78 males and 30 females) with multiple myeloma who underwent autologous stem cell transplantation (ASCT). The median age of patients was 52 years (range, 26-68 years). High-dose melphalan (200 mg/m(2)) was used for conditioning. In all, 66 (61%) patients had evidence of chemo-sensitive disease before transplant. After ASCT 79.6% of patients responded: complete response 36%, very good partial response 29.6%, and partial response 13.9%. Complete response rate was higher for patients with chemo-sensitive disease; 33 of 66 (50.0%) patients achieved complete response compared with 7 of 42 (14.3%) patients with progressive disease, P<0.01. Response rates to ASCT were significantly low for patients with Hb 5.5 mg/l, International Staging System stage III at diagnosis and >12 months interval from diagnosis to transplant. Grade III-IV mucositis was the major regimen-related toxicity. At a median follow-up of 70 months, the median overall survival and event free survival (EFS) were 71 and 42 months, respectively. Estimated overall survival and EFS at 60 months were 54.4+/-0.05% (s.e.) and 49.3+/-0.05% (s.e.), respectively. Survival was significantly better for patients with pre-transplant chemo-sensitive disease and for those who achieved complete response following transplant.     

IgD multiple myeloma—a clinical profile and outcome with chemotherapy and autologous stem cell transplantation

IgD myeloma accounts for 2% of myeloma subtypes and has higher incidence of complications and a poorer outcome. The characteristics and outcomes of 25 patients with IgD myeloma (2.6% of all myeloma patients), including 11 patients treated with autologous stem cell transplantation (ASCT) are reported. The presenting features were not unique for myeloma, but it appears that the commonest presenting symptom was bone pain in 20 (80%) patients. Other associated disorders were B-CLL in —1 patient and hairy cell leukemia in another. Three patients had a marked increase in bone marrow reticulin. Three (out of a total of 9) patients had 13q deletion (1 by cytogenetics and 2 by interphase fluorescence in situ hybridisation [FISH]), while 2 patients had a complex karyotype. A total of 11 patients were treated with ASCT, while 14 patients had chemotherapy alone. The response to treatment was: in the ASCT group 2 had a complete response (CR) and 9 had a good partial response (PR), while in the chemotherapy group 6 had a good PR with no CRs. The median overall survival (OS) and progression-free survival (PFS) after autologous peripheral blood stem cell transplantation (APBSCT) has not yet been reached after a median follow up of 4 years. The median PFS after chemotherapy was 1.23 years (95% CI 1.02–1.44). The mean OS transplantation was 5.09 years compared with 2.03 years for those treated with chemotherapy alone. However, this difference was not statistically significant (log rank p=0.09). This small series appears to suggest that outcome for IgD myeloma remains poor with chemotherapy and appears to be superior with ASCT, and larger studies are needed to confirm these findings.     

Mikulicz’s disease with severe thrombocytopenia following autologous stem cell transplantation in a multiple myeloma patient

We report the first case of Mikulicz’s disease (MD) occurring 2 years after autologous peripheral blood stem cell transplantation (PBSCT) for multiple myeloma (MM). A 70-year-old man developed bilateral enlargement of parotid and submandibular glands. The patient had previously received 2 courses of autologous PBSCT for IgG-κ type MM, and had been stable for 2 years. This salivary gland enlargement was initially felt to represent a recurrence of MM, since along with gland swelling, IgG was also elevated. However, repeated biopsy of the left submandibular gland revealed chronic sclerosing sialadenitis rather than plasmacytoma. Results of salivary gland scintigraphy, serological testing, and absence of sicca symptoms also supported the diagnosis of MD. Concurrently, the patient developed severe thrombocytopenia (0.8 × 10⁴/μl). Bone marrow biopsy showed abundant megakaryocytes, suggesting enhanced platelet destruction. After high-dose steroid and immunoglobulin therapy, the platelet count gradually returned to normal with complete resolution of the salivary gland enlargement. No apparent signs of MM recurrence were documented during these clinical events.     

Post-remission treatment for adult patients with acute lymphoblastic leukemia in first remission: is there a role for autologous stem cell transplantation?

Allogeneic stem cell transplantation (alloSCT) or autologous SCT (autoSCT) and intensive consolidation/intensification courses plus maintenance chemotherapy for 1 to 2 years are currently the major options for post-remission treatment of adult patients with acute lymphoblastic leukemia (ALL) in first remission. Comparison of their value with respect to relapse prevention, disease-free survival, and overall survival has been impossible until recently when the results of several randomized trials became available. Herein, we try to dissect data from these randomized trials to evaluate the role of autoSCT in patients with ALL in complete remission. Five prospectively randomized trials were found in which patients with a family donor were eligible for an alloSCT and the remaining patients were randomized between autoSCT and continuation chemotherapy. In addition, in two prospectively randomized trials all patients with a donor were eligible for an alloSCT and the remaining patients were eligible for autoSCT. Using intention to treat, in the majority of ALL studies alloSCT is superior to autoSCT or intensive continuation chemotherapy. It still has to be determined which subgroups of ALL benefit most of allogeneic transplantation, since in some trials the advantage of allogeneic transplantation was confined to the standard-risk ALL patients and in other trials to the high-risk patients. With respect to the role of autoSCT compared to continuation chemotherapy, both treatment modalities show equal, although for high-risk ALL inferior, overall survival chances. In one large trial the disease-free survival in the autoSCT arm was inferior to that in the chemotherapy arm. This finding may eventually have an impact on the overall survival rate. Currently, the main benefit of autoSCT may be its short duration compared with the continuation chemotherapy regimen.     

Benefit from autologous stem cell transplantation in primary refractory myeloma? Different outcomes in progressive versus stable disease

Background

Several studies of autologous stem cell transplantation in primary refractory myeloma have produced encouraging results. However, the outcome of primary refractory patients with stable disease has not been analyzed separately from the outcome of patients with progressive disease.

Design and Methods

In the Spanish Myeloma Group 2000 trial, 80 patients with primary refractory myeloma (49 with stable disease and 31 with progressive disease), i.e. who were refractory to initial chemotherapy, were scheduled for tandem transplants (double autologous transplant or a single autologous transplant followed by an allogeneic transplant). Patients with primary refractory disease included those who never achieved a minimal response (≥25% M-protein decrease) or better. Responses were assessed using the European Bone Marrow Transplant criteria.

Results

There were no significant differences in the rates of partial response or better between patients with stable or progressive disease. However, 38% of the patients with stable disease at the time of transplantation remained in a stable condition or achieved a minimal response after transplantation versus 7% in the group with progressive disease (P=0.0017) and the rate of early progression after transplantation was significantly higher among the group with progressive disease at the time of transplantation (22% versus 2%; P=0.0043). After a median follow-up of 6.6 years, the median survival after first transplant of the whole series was 2.3 years. Progression-free and overall survival from the first transplant were shorter in patients with progressive disease (0.6 versus 2.3 years, P=0.00004 and 1.1 versus 6 years, P=0.00002, respectively).

Conclusions

Our results show that patients with progressive refractory myeloma do not benefit from autologous transplantation, while patients with stable disease have an outcome comparable to those with chemosensitive disease. (ClinicalTrials.gov:{"type":"clinical-trial","attrs":{"text":"NCT00560053","term_id":"NCT00560053"}}NCT00560053)     

Rituximab long-term maintenance therapy after autologous stem cell transplantation in patients with B-cell non-Hodgkin’s lymphoma

Treatment of B-cell non-Hodgkin’s lymphomas (NHL) with either Rituximab alone or in combination with cytotoxic chemotherapy has been effective without major side effects. Thus, Rituximab maintenance therapy after autologous peripheral blood stem cell transplantation (PBSCT) might represent an improvement in NHL therapy. We therefore retrospectively analyzed the efficacy and side effects of monthly long-term Rituximab maintenance therapy after PBSCT in 27 patients with NHL. In median 10 infusions of Rituximab were given after PBSCT in time intervals of 1 month. Molecular monitoring of t(14;18) was performed using nested as well as quantitative real time polymerase chain reaction (RT-PCR) based on the LightCycler technology. Side effects according to common toxicity criteria (CTC) > II did mainly affect the hematopoietic system. In total, 10 patients (37%) suffered form grade III–IV hematotoxicity. Except for two patients with cutaneous Varicella–Zoster infection no serious infectious complications (CTC grade III/IV) occurred. No patient died because of treatment-related causes. This adverse event data compared favorably to the published data. Three patients had t(14;18) nested RT-PCR positive results before Rituximab therapy and converted to negativity after Rituximab therapy. We conclude that a prolonged Rituximab maintenance therapy after PBSCT with monthly administration is reliable and safe.     

What is the role of up-front autologous stem cell transplantation in mantle cell lymphoma?

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Ideal or actual body weight to calculate CD34+ cell doses for autologous hematopoietic stem cell transplantation?

The number of CD34+ cells infused influences the speed of hematologic recovery post-transplant. There are limited data on whether ideal (IBW) or actual (ABW) body weight should be used to calculate CD34+ cell dose. We compared the correlation between recovery to 0.5 x 10(9)/l neutrophils and the CD34+ cell dose based upon ABW as well as IBW in 87 patients autografted for cancer. ABW was >or=25% over IBW in 43% of patients. The median number of CD34+ cells administered was 3.6 x 10(6)/kg ABW and 4.2 x 10(6)/kg IBW. The time to neutrophil recovery was 8-15 days (median 10). There was a stronger inverse correlation between CD34+ cell dose/IBW and neutrophil recovery (r(2)=0.308; P<0.0001) than between CD34+ cell dose/ABW and neutrophil recovery (r(2)=0.267; P<0.0001). The median time to neutrophil recovery was comparable for those receiving >or=2 x 10(6)/kg CD34+ cells/kg IBW as well as ABW (10 days) and those receiving >or=2 x 10(6)/kg CD34+ cells/kg IBW but <2/kg ABW (10 days), but was significantly slower for those receiving <2 x 10(6)/kg CD34+ cells/kg IBW (12 days). These data show that the CD34+ cell dose based on IBW is a better predictor of neutrophil recovery after autotransplantation.     

High-dose thiotepa,etoposide and carboplatin as conditioning regimen for autologous stem cell transplantation in patients with high-risk Hodgkin’s lymphoma

Abstract

Background: Autologous stem cell transplantation (ASCT) generally provides good results in Hodgkin’s lymphoma (HL). We studied a high-dose chemotherapy regimen based on thiotepa, etoposide and carboplatin (TECA).

Methods: Fifty-eight patients with advanced HL were treated with thiotepa, etoposide and carboplatin for transplant induction.

Results: The overall response rate was 79·3% (39 CR: 67·2%; and 7 PR: 12·1%); 12 patients (20·1%) were non-responders. The 5-year overall survival rate was 77·6%; five initially responder patients relapsed within the first 5 years of follow-up and underwent salvage therapy.

Conclusion: The TECA conditioning regimen for ASCT in HL results in a good anti-HL effect, positive response to treatment and high 5-year overall survival rate. It was also well tolerated and did not induce excessive toxicity, suggesting that TECA may be a very useful conditioning regimen for HL.     

The autologous bone marrow mononuclear cell transplantation by intracoronary route treat patients with severe heart failure after myocardial infarction

Objective To investigate the chronic effects of intracoronary autologous bone marrow mononuclear cell (BM-MNCs) transplantation in patients with refractory heart failure (RIHF) after myocardial infarction. Methods Thirty patients with RIHF (LVEF<40%) were enrolled in this nonrandomized study, autologous BM-MNCs (5.0±0.7)×107 were transplanted with via infarct-related coronary artery in 16 patients and 14 patients received     

Interleukin-2 and granulocyte–macrophage–colony-stimulating factor immunomodulation with high-dose chemotherapy and autologous hematopoietic stem cell transplantation for patients with metastatic breast cancer

Immunomodulation with cytokines was used to improve the result of high-dose chemotherapy (HDC)/autologous hematopoietic stem cell transplantation (AHST). We examined the use of IL-2 and growth factors for mobilization, ex vivo activation of peripheral blood stem cell (PBSC) and maintenance therapy after HDC/AHST in metastatic breast cancer. Eligible patients with metastatic breast cancer for HDC/AHST were assigned to 1 of 3 protocols for PBSC mobilization: G-CSF (group 1); IL-2 + G-CSF (group 2); or IL-2 + G-CSF + GM–CSF (group 3). HDC with cyclophosphamide, carmustine and thiotepa was given from day ?7 to ?5. PBSCs were treated ex vivo with IL-2 for 24 h and reinfused on day 0. Maintenance therapy included low-dose IL-2, followed by 2 courses of intermediate-dose IL-2. GM–CSF was given from day 1 until neutrophil recovery. Thirty-four patients (10 in group 1, 14 in group 2, and 10 in group 3) were included. Comparable numbers of CD34⁺ cells were collected from all 3 groups; incremental increases of CD3⁺ cells were collected from groups 1 to 2 and to 3 (p = 0.03). Major adverse effects from IL-2 were fever, hypotension and fatigue; no treatment-related mortality was seen. At a median follow-up of 790.5 days (range 150–2,722 days), median progression-free survival was 434 days and median overall survival was 1,432 days. Estimated 3-year progression-free and overall survival rates were 31 and 57%. Our study suggested that the use of IL-2 and growth factors immunomodulation with HDC/AHST was feasible with comparable survival rates.     

Allogeneic stem cell transplantation in patients with de novo diffuse large B-cell lymphoma who experienced relapse or progression after autologous stem cell transplantation: a Korea–Japan collaborative study

Patients with diffuse large B-cell lymphoma (DLBCL) who failed autologous stem cell transplantation (auto-SCT) generally have a poor prognosis. Allogeneic stem cell transplantation (allo-SCT) has been implemented to overcome this problem. We report clinical outcomes of allo-SCT in patients with de novo DLBCL who failed auto-SCT from four hospitals in Korea and Japan. Thirty patients were included. The median age was 39 (range, 22–59) years. The 5-year event-free survival (EFS) and overall survival (OS) after allo-SCT were 37.9 % and 42.6 %, respectively. There was only a single event beyond 12 months in the Kaplan-Meier curve of EFS. Non-relapse mortality (NRM) was reported in five patients (16.7 %). In the multivariate analysis, the risk factors for EFS were prior chemotherapy lines ≥ 5 (p?=?0.010) and chemo-resistant disease (p?=?0.007). The risk factors for OS were chemo-resistant disease (p?=?0.024) and Eastern Cooperative Oncology Group performance status 2 (p?=?0.005). NRM was associated with prior chemotherapy lines ≥ 5 (p?=?0.042), chemo-resistant disease (p?=?0.009), and poor performance status (p?<?0.001). In conclusion, allo-SCT showed considerable efficacy in patients with DLBCL whose disease was relapsed or progressed after auto-SCT. Our data suggest that allo-SCT could be a viable treatment option if patients have fewer lines of prior chemotherapy, chemo-sensitive disease, and/or good PS.     

(18)F-deoxyglucose PET: useful in the management of patients with stem cell transplantation for lymphoma?

(18)F-deoxyglucose (FDG) positron emission tomography (PET) and more recently FDG PET/computed tomography (CT) has become an important tool in the management of patients with Hodgkin and non-Hodgkin lymphoma. It adds metabolic and functional information to conventional anatomical imaging, mainly assessed by CT. Especially for the detection of early response to treatment and prognostic considerations, this type of information seems better suited than anatomical information. Consequently, the ability of FDG PET to predict the outcome in patients with stem cell transplantation (SCT) for lymphoma has been tested in several studies. Results in patients with autologous SCT have been promising, and pretransplant FDG PET is likely to become routine in this group of patients. The evaluated study investigates, for the first time, the predictive value of pretransplant FDG PET in allogeneic SCT, as well as the utility of FDG PET for the follow-up of these patients. All 80 patients included in the prospective study had reduced-intensity conditioning. In contrast to FDG PET before autologous SCT, there was no correlation at all between pretransplant FDG PET results and the outcome after allogeneic SCT. This reflects the fact that other or additional reasons, especially the graft-versus-leukemia effect, are substantial for the outcome of allogeneic SCT in comparison with autologous SCT. Follow-up with FDG PET after reduced-intensity allogeneic SCT was significantly more sensitive than CT to detect disease progression or relapse, and was useful in guiding treatment in the situation of disease relapse.