Multiple Myeloma In Complete Remission Research Articles

Conditioning regimen using busulfan plus melphalan in hematopoietic stem cell transplantation

Conditioning regimen using busulfan plus melphalan in hematopoietic stem cell transplantation

Multiple Myeloma In Complete Remission After Autologous Stem Cell Transplantation: Impact of Bone Marrow Plasma Cell Assessment by Conventional Morphology on Disease Progression

AbstractAbstract 2946 Background:The achievement of complete remission (CR) is the crucial step for a long-lasting response and prolonged survival after autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM). The European Group for Blood and Marrow Transplantation (EBMT) criteria for CR include the negativity of serum and urine immunofixation (IFE) and less than 5% of bone marrow plasma cells (BMPCs). Additionally, the International Myeloma Working Group (IMWG) has even proposed a stringent CR category, which requires to rule out the clonal nature of the BMPCs. However, few studies have addressed this issue in patients with MM and negative IFE. The aim of the present study was to determine the impact of plasma cell count in the bone marrow aspirate on the long-term outcome of patients with MM with negative IFE after ASCT. Methods:Thirty-five patients (16M/19F; median age at ASCT 55 years, range 26–68) with MM who underwent ASCT from March 1994 to December 2008, were studied. All patients had achieved a negative serum and urine IFE after high dose therapy with melphalan-based regimens. Bone marrow aspirate was performed when negative serum and urine IFE was achieved and at least three months from ASCT (median 3.24 months). The analysis was based on microscopic revision for May-Grünwald-Giemsa stained bone marrow smears performed according to standard procedures. BMPC percentage was calculated independently by two observers counting 500 bone marrow total nucleated cells in random areas from two different slides (1000 cells on each patient). Results:Median BMPCs percentage was 0.8 (range 0.1–5.8). Only two patients had more than 3% BPMCs. These results are in contrast with a recent report from the Mayo Clinic group, where 14% of the patients with MM and negative IFE had 5% or more BMPCs. In univariate Cox-model regression analysis, the number of BMPCs significantly correlated with progression-free survival (PFS)(p=0.021) with no impact on overall survival (OS)(p=0.92). This statistical significance on PFS was retained in the multivariate analysis, when baseline prognostic factors such as age, hemoglobin level, serum creatinine, β2-microglobulin and Durie-Salmon stage were added to the model (p=0.003). To establish the best predictive cut-off for progression and survival, a receptor-operator curve (ROC) analysis was developed. It showed the value of 1.5% BMPCs, with a sensitivity of 53%, specificity of 90% and area under the curve of 0.66 for predicting progression. Ten patients had more than 1.5% BMPC, and 25 equal or less than 1.5% BMPC. Median PFS was 8.5 years (CI 95% 2.6 to 14.3) and was not reached in patients with ≤1.5% BMPCs versus 3.1 years in patients with >1.5% BMPCs, with a hazard ratio probability to progression of 3.02 (CI 95% 1.18 to 9.71)(p=0.016) in the group with more than 1.5% of BMPCs (Figure 1). Median OS was not reached in patients with ≤1.5% compared with a median of 9.7 years in those with more than 1.5% BMPCs (p=0.195) (Figure 2). It is likely that serological CR with very low percentage of BMPCs (i.e. ≤1.5%) is equivalent to negative MRD assessed by MFC or molecular studies. In fact, all 8 patients in continued CR between 9 and 16 years beyond ASCT (“operational cures”) are in the group with ≤1.5% BMPCs, while all patients in the group with >1.5% BPMC have relapsed within the first 9 years from ASCT (Figure 1). Conclusion:The percentage of BMPCs in patients with MM in CR after ASCT is a strong predictor of progression. Bone marrow morphology examination is an easy, inexpensive, and non-time consuming test and it should be the first step in the estimation of the residual tumor mass in patients with MM in CR after ASCT. [Display omitted] [Display omitted] Disclosures:Rosiñol:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Cibeira:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Blade:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Oligoclonal Bands In Patients with Multiple Myeloma In Complete Remission After Induction Chemotherapy: Strong Association with the Use of Novel Agents

AbstractAbstract 2945 Background:The emergence of oligoclonal bands is a well recognized event after autologous stem cell transplantation in multiple myeloma (MM). These atypical serum immunofixation (IFE) patterns are associated with good prognosis, likely due to a durable immune reconstitution. They can appear with novel immunomodulatory drugs such as lenalidomide, but its prevalence with other induction treatments has not been reported. Aims:To determine the prevalence of serum and/or urine immunoglobulin oligoclonality in patients with MM in CR after primary therapy with cytotoxic agents or with new induction chemotherapy regimens incorporating novel drugs up-front. Methods:Thirty-three patients (15M/18F; median age at diagnosis 59 years, range 25 to 89) with MM in CR after different induction regimens were studied. Initial baseline demographics, clinical and laboratory data, treatment and follow-up were collected. An oligoclonal band was defined as the presence of a serum and/or urine IFE monoclonal spike different either in heavy and/or light chain component from the original myeloma protein. Results:The initial clinical and laboratory findings as well as the induction treatments are shown in the table 1. Eighteen patients (54.5%) received induction with conventional chemotherapy and 15 (45.5%) with novel agents. In the latter group, the induction regimen was based on combinations of glucocorticoids with lenalidomide (26.7%), thalidomide (26.7%), bortezomib (33.3%) or bortezomib plus lenalidomide (13.3%). In the overall series, 11 out of the 33 patients (33.3%) developed an oligoclonal band. These abnormal bands observed in the IFE pattern lasted from 2.2 to 55.7 months (median 11.5 months).Four patients (36.4%) had a fluctuating oligoclonal pattern during their follow-up while the remaining showed a single oligoclonal immunoglobulin. The most frequent isotype seen in oligoclonal bands was IgG-κ (72.7%), as it was previously described after ASCT. In the group treated with cytotoxic agents, the prevalence of oligoclonal bands was observed in 2 patients (11.1%), both of them had been treated with cyclophosphamide and dexamethasone. In contrast, induction with novel drugs resulted in 9 out of 15 patients (60%) developing oligoclonal bands in serum and/or urine (chi-square test 2-sided, p=0.003). Interestingly, five patients with oligoclonal humoral response have already relapsed (45.5%). In four of them, relapse was coincident with the disappearance of the previous oligoclonality, while in the remaining case the disappearance of the oligoclonality preceded relapse in six months. Conclusions:This is the first report showing a significantly different frequency of oligoclonal bands in patients with MM in CR after conventional cytotoxic therapy versus induction incorporating novel agents. This difference is likely due to a greater antimyeloma effect, a strongest immune reconstitution resulting from the effect of novel drugs, or both. With the progressive use of these drugs, the CR rate and consequently the proportion of patients who develop an oligoclonal immune response with oligoclonal bands will likely increase. However, the mechanism associated with the emergence of the oligoclonal bands as well as its prognostic impact is still unknown and deserve further investigation.Table 1Patient characteristicsVariableTotal group (n=33)Cytotoxic drugs group (n=18)Novel drugs group (n=15)Median age, y (range)59ü(25–89)57.9ü(25–89)61.4ü(47–79)Male/female, n15/188/107/8Heavy-chain component (%)IgG27.316.740IgA27.327.826.7Only light chains30.338.920IgD12.116.76.7IgM306.7Light-chain (%)κ48.55066.7λ51.55033.3 Disclosures:Cibeira:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Rosiñol:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Blade:Janssen-Cilag: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Emergence of oligoclonal bands in patients with multiple myeloma in complete remission after induction chemotherapy: association with the use of novel agents

The emergence of oligoclonal bands is associated with a favorable outcome after autologous stem cell transplantation in multiple myeloma. The aim of this study was to determine the prevalence of immunoglobulin oligoclonality in 33 patients with multiple myeloma in complete remission achieved with primary therapy with either cytotoxic agents (n = 18, 54.5%) or new induction regimens incorporating novel drugs (n = 15, 45.4%). Eleven patients (33.3%) developed oligoclonal bands. In the group treated with novel agents, this oligoclonal immune response was observed in 60% (9 of 15) of the patients versus only 11.1% (2 of 18) of those given cytotoxic therapy (P = 0.003). This is the first report showing a different frequency of oligoclonal humoral response in patients in complete remission achieved after conventional cytotoxic therapy versus induction incorporating novel agents. This difference could be due to a higher antitumor effect associated with the use of novel drugs, a stronger immune reconstitution, or both.

IgA pemphigus associated with monoclonal gammopathy completely resolved after achievement of complete remission of multiple myeloma with bortezomib, cyclophosphamide and dexamethasone regimen

Monoclonal gammopathy-associated IgA pemphigus is a debilitating skin disorder with inconsistent response to treatment. A 61-year-old woman with IgA pemphigus and monoclonal gammopathy of unknown significance had been treated unsuccessfully with cyclophosphamide/dexamethasone and then with rituximab. When the monoclonal gammopathy progressed to multiple myeloma, the patient received treatment with cyclophosphamide/doxorubicin/dexamethasone but there was no clinical response. Second-line therapy with a thalidomide/cyclophosphamide/dexamethasone combination led to severe exacerbation of the skin disorder. However, therapy with a combination regimen that included bortezomib, cyclophosphamide and dexamethasone resulted in complete and durable remission of multiple myeloma and IgA pemphigus. This suggests that bortezomib-based therapy is useful for the treatment of the rare dermatologic disorder associated with IgA gammopathy.

A Case of Multiple Pulmonary Plasmacytomas after Complete Remission of Multiple Myeloma

Extramedullary plasmacytoma (EMP) is a rare disorder that typically occurs in the upper airway. Although the condition rarely arises in the lungs, a few cases have been reported. Here, we report a case of pulmonary plasmacytoma in 66-year-old man, who had been treated with VAD (vincrestine, adriamycin, dexamethasone) chemotherapy for multiple myeloma. The patient had been declared clear of multiple myeloma after 4 cycles of chemotherapy. Three months later, the patient had multiple masses visible on computed tomography (CT) and on positron emission tomography-computed tomography (PET-CT) with hot uptake. Subsequent studies using CT-guided needle biopsy and immunohistochemical stain showed pulmonary plasmacytoma. Bone marrow biopsy, serum, and urine M protein tests were repeated, showing no evidence of multiple myeloma. Pulmonary plasmacytomas, as extramedullary plasmacytomas, were considered an isolated manifestation of multiple myeloma recurrence. We treated the patient with concurrent chemoradiotherapy and the pulmonary plasmacytomas regressed dramatically.

Abnormal serum free light chain ratio in patients with multiple myeloma in complete remission has strong association with the presence of oligoclonal bands: implications for stringent complete remission definition

AbstractThe prevalence of an abnormal serum free light chain (FLC) ratio in 34 patients with multiple myeloma in complete response (CR) after hematopoietic stem cell transplantation was studied. Fourteen of 34 patients (41.2%) showed an abnormal FLC ratio. The frequency of abnormal FLC ratio in patients with or without oligoclonal bands was 72.7% versus 26%, respectively (P = .023). The median value of FLC ratio was 2.55 (95% confidence interval, 1.89-3.20) in patients with oligoclonal bands versus 0.87 (95% confidence interval, 0.70-1.04) for those with no oligoclonal bands (P = .011). This is the first report showing that the presence of oligoclonal bands in patients with multiple myeloma in CR frequently results in an abnormal FLC ratio. Because an oligoclonal immune response is associated with a good outcome, our results question the current definition of stringent CR and support that the prognostic impact of oligoclonal bands should be also assessed on multivariate analysis.

Complete remission in multiple myeloma examined as time-dependent variable in terms of both onset and duration in Total Therapy protocols

AbstractLandmark analyses are used to investigate the importance for survival of achieving complete response (CR), an important initial goal of myeloma therapy. With median times to CR in Total Therapy (TT) trials of approximately 1 year, this approach excludes a sizeable fraction of patients dying before such a landmark. To permit inclusion of all trial participants, we investigated the prognostic implications of both onset and duration of CR as time-dependent variables. Superseding the adverse effects of cytogenetic abnormalities and other standard prognostic parameters, both failure to achieve CR (non-CR) and, especially, loss of CR (los-CR) were independently associated with inferior survival in TT1, TT2, and TT3 protocols. In the context of gene array–defined risk, available in TT2 and TT3 subsets, both los-CR and non-CR terms were retained in the survival model as dominant adverse variables, stressing the prognostic importance of sustaining CR status, especially in high-risk disease.

天然型インターフェロンα (HLBI)をMelphalan/Prednisolone大量間欠療法に併用し完全寛解を達成した多発性骨髄腫の1例

天然型インターフェロンα (HLBI)をMelphalan/Prednisolone大量間欠療法に併用し完全寛解を達成した多発性骨髄腫の1例

Plasmocitoma testicular bilateral secundario. Aportación de un caso y revisión de la literatura

Testicular plasmacytoma is a very unfrequent plasma cells neoplasm. It is usually an incidental autopsy finding devoid of clinical expression, but it presents sometimes as part of a multiple myeloma and is exceptionally its only location. Bilateral involvement is extremely unfrequent. We report the case of a 58 years old man diagnosed with multiple myeloma in complete remission who complains about progressive enlargement of both testicles. After ultrasonography and PAAF, bilateral testicular plasmacytoma is diagnosed. Treatment includes surgery (orchiectomy), radiotherapy and chemotherapy. Prognostic is worse when multiple myeloma is associated.

Rapid complete remission in multiple myeloma with bortezomib/thalidomide/dexamethasone combination therapy following development of tumor lysis syndrome

Rapid complete remission in multiple myeloma with bortezomib/thalidomide/dexamethasone combination therapy following development of tumor lysis syndrome

Complete remission of multiple myeloma after autoimmune hemolytic anemia: Possible association with interferon‐α

A patient with multiple myeloma (MM) was being maintained on human recombinant interferon-alpha (INF-alpha) after VAD and autologous bone marrow transplantation (pretreated with melphalan). An episode of immune thrombocytopenia and (Coombs positive) autoimmune hemolytic anemia (AIHA) was noted while on maintenance INF-alpha, which remitted when it was withdrawn. Following this event, he achieved a state of stable disease that persists (more than 3 years) with no specific myeloma treatment. This sequence of events suggests a relationship between an immunological reaction induced by INF-alpha and the prolonged phase of stable disease.

P.2.a.014 Rapid effect of escitalopram in a behavioural model of depression: the chronic escape deficit

The chronobiological circadian behaviour in serum levels of β-microglobulin has been investigated in three groups of subjects: (A) 6 healthy controls; (B) 6 patients with untreated multiple myeloma; (C) 6 patients with multiple myeloma in complete remission after polychemotherapy. From all subjects, under the same standard life conditions, venous blood samples were drawn at 4-hour intervals starting from midnight during the span of a whole day. Circulating serum β2-microglobulin levels were determined by RIA method. The time-related data were analyzed by chronograms and the “mean-group cosinor” method. A significant circadian rhythm for serum β2-microglobulin was detected in the control group, with a peak in the morning hours, and in untreated patients, with a peak in the afternoon hours. No significant rhythm was found in treated patients with multiple myeloma. A significant mesor reduction was noted in patients with complete remission, correlated with the absence of circadian rhythm, in respect to untreated patients. These data suggests that serum levels of β2-microglobulin could be related to the neoplastic plasma cell proliferation and to the effect of therapy, and that the circadian evaluation could be used as a guide in monitoring myeloma patients.

Congestive heart failure: revealing light chain deposition disease

We report a case of light chain deposition disease associated with multiple myeloma revealed by congestive heart failure. Endomyocardial biopsy showed Congo red negative deposits and lambda light chain deposits by the immunofluorescence method. After chemotherapy with melphalan and prednisone, complete remission of multiple myeloma and major improvement in cardiac condition were observed.

Drug resistance of secondary acute myeloid leukemia with megakaryoblastic features and p190 BCR-ABL rearrangement

A 46-year-old female presented with acute myeloid leukemia during complete remission of multiple myeloma after extensive treatment with alkylating agents. Leukemic blasts expressed CD34, platelet esterase and gp IIIa. RT–PCR analyses of peripheral blood cells detected a p190 type BCR-ABL rearrangement and high levels of MDR1. The patient expired during neutropenia shortly after induction chemotherapy. Autopsy revealed persistent blasts in the bone marrow, spleen and liver. 'Secondary' acute myeloid leukemia with megakaryoblastic features and p190-type BCR-ABL rearrangement has not previously been reported. The possibility that the combination of a BCR-ABL rearrangement with overexpression of MDR1 may have contributed to the treatment-refractory course is discussed.

Diurnal variations of serum β2-microglobulin in multiple myeloma

The chronobiological circadian behaviour in serum levels of β-microglobulin has been investigated in three groups of subjects: (A) 6 healthy controls; (B) 6 patients with untreated multiple myeloma; (C) 6 patients with multiple myeloma in complete remission after polychemotherapy. From all subjects, under the same standard life conditions, venous blood samples were drawn at 4-hour intervals starting from midnight during the span of a whole day. Circulating serum β2-microglobulin levels were determined by RIA method. The time-related data were analyzed by chronograms and the “mean-group cosinor” method. A significant circadian rhythm for serum β2-microglobulin was detected in the control group, with a peak in the morning hours, and in untreated patients, with a peak in the afternoon hours. No significant rhythm was found in treated patients with multiple myeloma. A significant mesor reduction was noted in patients with complete remission, correlated with the absence of circadian rhythm, in respect to untreated patients. These data suggests that serum levels of β2-microglobulin could be related to the neoplastic plasma cell proliferation and to the effect of therapy, and that the circadian evaluation could be used as a guide in monitoring myeloma patients.