Sequential radioimmunotherapy with tositumomab/Iodine I131 tositumomab followed by CHOP for mantle cell lymphoma demonstrates RIT can induce molecular remissions

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7560-7560 ◽  
Author(s):  
A. D. Zelenetz ◽  
A. Noy ◽  
N. Pandit-Taskar ◽  
M. Scordo ◽  
I. Rijo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
Alternative Therapy ◽  
Active Agent ◽  
Initial Therapy ◽  
High Dose ◽  
Chop Chemotherapy ◽  
Mantle Cell

7560 Background: Mantle cell lymphoma remains a clinical challenge particularly for pts not candidates for consolidation with ASCT or treatment with leukemia induction regimens. Methods: We investigated sequential radioimmunotherapy (RIT) cytoreduction with tositumomab/Iodine I131 tositumomab followed by CHOP chemotherapy as initial therapy for patients either ineligible for or unwilling to undergo high dose therapy and stem cell transplantation. In addition, pts had to have less than 25% of the intratrabecular bone marrow space involved with lymphoma. Results: Twenty-five patients (pts) were enrolled but only 24 were treated with the therapeutic dose of RIT because a manufacturing problem prevented the treatment of one patient. The median age was 66 (45–80), there were 23 men and 2 women. All patients had advanced stage (III/IV) disease and bone marrow was involved in 48% and the GI tract was involved in 48% of the patients. The overall response rate (ORR) to RIT was 83% (CR/CRu 46%; PR 38%). Two pts withdrew consent following the RIT (and are censored from that point); 1 pt with disease progression requiring alternative therapy is included in EFS and OS analyses. Twenty-one pts proceeded to the CHOP consolidation and 19 completed planned therapy (1 pt died of a CVA; 1 pt chose not to complete chemotherapy after two cycles of CHOP). At the completion of delivered therapy the ORR was 86% (CR/CRu 67%, PR 19%). The median follow up is 2.1 years (0.7 to 4.2). The median EFS was 1.4 years though there have been no events beyond 1.7 years with 7 pts at risk; median OS has not been reached (92% at 2.1 years). Minimal residual disease (MRD) was evaluated with a clonotypic PCR (cPCR) capable of detecting about 1:105 tumor cells; this assay was informative in 17 pts. Following induction with RIT 6 pts (46%) were molecularly negative in blood and bone marrow. Despite the increase in clinical CR following CHOP consolidation, no additional pts became molecularly negative. Conclusions: RIT with tositumomab/iodine I131 tositumomab is a very active agent in the treatment of MCL; unfortunately, MRD is not effectively eliminated by subsequent CHOP chemotherapy. We are planning to explore chemotherapy induction followed by RIT. [Table: see text]

scholarly journals Update on mantle cell lymphoma

Blood ◽  
2018 ◽  
Vol 132 (16) ◽  
pp. 1647-1656 ◽  
Author(s):  
Kami Maddocks
Keyword(s):  
Mantle Cell Lymphoma ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
Response Duration ◽  
Standard Of Care ◽  
Initial Therapy ◽  
World Health ◽  
Molecular Features ◽  
Therapeutic Decisions ◽  
Mantle Cell

AbstractMantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma that is most commonly treated with combination chemo-immunotherapy at diagnosis because of the poor prognosis. More indolent presentations have been described including patients who can defer initial therapy without adverse impact on survival. The 2016 World Health Organization updated classification describes 2 major subtypes, classical and leukemic nonnodal MCL, each with unique molecular features and clinical presentations. Although there is no standard of care for MCL, aggressive chemo-immunotherapy regimens containing rituximab and cytarabine, followed by consolidation with autologous stem cell transplantation and maintenance rituximab, are the most used approach in young fit patients, and chemo-immunotherapy, followed by rituximab maintenance, is most commonly used in older patients. Despite the improvement in response durations with currently available therapies, patients will inevitably relapse. A number of targeted therapies are approved in the relapsed setting and are now under evaluation in combination with standard frontline therapy. Although the approval of ibrutinib changed the landscape of therapy for relapsed MCL, prognosis remains poor after progression on ibrutinib supporting the development of ibrutinib combinations to prolong response duration as well as the development of other novel agents for ibrutinib refractory disease. With ibrutinib being incorporated into initial therapy regimens, new options will be needed at relapse. Prognostic markers, such as minimal residual disease, have been shown to correlate independently with outcomes along with predicting relapse, with the potential to guide therapeutic decisions. The future treatment of MCL therapy will need to incorporate therapy based on risk-stratification and nonchemotherapeutic approaches.

T(11;14)(q13;q32) in Mantle Cell Lymphoma Patients Is Present Only on Mature Malignant Cells. Fluorescence-Activated Cell Sorting and Fluorescence in Situ Hybridization Analysis

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4405-4405
Author(s):  
Vladimir I. Vorobyev ◽  
Evgenii’ M Gretsov ◽  
Tatyana N Obukhova ◽  
Elena V Domracheva ◽  
Yuri Yu Lorie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
Mantle Cell Lymphoma ◽  
Cell Sorting ◽  
Cell Lymphoma ◽  
Acid Mixture ◽  
High Dose ◽  
Fish Analysis ◽  
Fluorescence Activated Cell Sorting ◽  
Mantle Cell

Abstract Abstract 4405 Background: Mantle cell lymphoma (MCL) is a distinct incurable B-cell neoplasm with a median survival of 3 to 5 years. t(11;14)(q13;q32) is the hallmark of the disease leading to overexpression of protooncogene cyclin D1. At least 60% of MCL patients have unmutated VH genes. Chemoresistance to conventional treatment and continuous disease relapses even after high dose therapy and autologous stem cell transplantation define the clinical course of the disease. A possible cause of this frequent failures may be that t(11;14)(q13;q32) occurs in early hematopoietic precursors, capable of multilineage differentiation. Aim: evaluation of t(11;14)(q13;q32) in different hematopoietic lineages of MCL patients. Methods: Bone marrow mononuclears from 12 MCL patients (including pleomorphic and blastoid variants) were sorted by Fluorescence-Activated Cell Sorting (BD FACSVantage SE) to divide the following cell lineages: CD45+CD34+ (progenitor cells); CD45+CD5+CD19+light chain Ig (mantle cell lymphoma); CD45+CD5-CD19+ (normal B-cells); CD45+CD14+ (monocytes); CD45+CD3+ (T-cells); CD45-GlyA+ (erythrokaryocytes) and granulocytes by light scattering, excluding CD14+CD45+ cells. The purity of sorted cells was checked by flow cytometry (BD FACSCanto II) and correlated to the number of sorted cells – if there were more than 50 thousands cells the purity was more than 92% (usually more 97%), but if there were less than 20 thousands cells the purity was 80% (never less). After sorting cells in the test-tube were washed from the PBS, fixed in methanol and glacial acetic acid mixture and layered onto slides by Cytospin centrifuge (Cellspin II Tharmac). The probes have been denatured at 75°C for 2 minutes, and hybridized with dual fusion LSI IGH-CCND1 probes (Vysis Inc.) at 37°C for 17–20 hours. Signals were visualized with Olympus IX-61 microscope with triple filter cube (DAPI / FITC / TexasRed). Results: t(11;14)(q13;q32) was present in 97% of sorted mantle cell lymphoma cells (range 84–100%), whereas in cells of all other lineages including normal B-cells t(11;14)(q13;q32) was not found at all. However, direct assessment of t(11;14)(q13;q32) in CD34+CD45+ cells and in normal B-cells was difficult due to the small number of these cells. In one case (classic variant MCL) we have sorted two “independent” cell populations 1 log different in the level of expression CD5: CD5dimCD19+ and CD5+CD19+. In both subpopulations t(11;14)(q13;32) was detected in 98,5% cell nuclei, indicating no correlation between CD5 level and fusion gene expression. In three cases using together FACS and FISH we were able to detect the population of MCL cells in bone marrow as small as 0,1–0,05%, whereas histology examination and standard FISH analysis failed to detect bone marrow involvement. Conclusion: Out data give evidence for the absence of t(11;14)(q13;q32) in early hematopoetic cells. FACS allows increase FISH sensitivity in 100–1000 times. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Minimal Residual Disease Monitoring By 8-Color Flow Cytometry in Mantle Cell Lymphoma Is Complementary to Q-PCR Monitoring and Will Facilitate Pre-Emptive Treatment: An EU-MCL and Lysa Study

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1657-1657
Author(s):  
Morgane Cheminant ◽  
Stephanie Schmit ◽  
Aurore Touzart ◽  
Coralie Derrieux ◽  
Marie-Hélène Delfau-Larue ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Flow Cytometry ◽  
Mantle Cell Lymphoma ◽  
Patient Management ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
Clinical Relapse ◽  
Color Flow ◽  
Mantle Cell ◽  
Minimal Residual

Abstract Introduction: Mantle Cell Lymphoma (MCL) is characterized by frequent blood and bone marrow involvement. It has been demonstrated that use of Minimal Residual Disease (MRD) quantification in blood and/or bone marrow might be helpful in patient management. Gold standard MRD is based on Q-PCR clone specific amplification of IgH VDJ or IgH-BCL1 rearrangements, but these are relatively complex and time consuming and over half of the positive results are in a grey zone of borderline positivity. Flow cytometry (FCM) is more rapid and better adapted to individual patient management if quantitatively reproducible, but insufficiently sensitive when only 4 colors are used. We therefore developed a universal, 8-color, EuroFlow inspired, FCM strategy, which we compared with classical Q-PCR MRD in 61/97 patients included in (and 1 treated according to) the EU-MCL Younger and Elderly prospective trials who underwent Q-PCR MRD monitoring at Necker Hospital. Method: Q-PCR MRD from IgH VDJ (n=92) or BCL1-IgH (n=5) was performed prospectively from ficolled blood (PB) or bone marrow, from which residual material was cryopreserved in DMSO for FCM quantitation, using 10 antibodies labelled with 8 fluorochromes for positive and negative (CD45, CD19, CD5, LAIR1, CD11a, IGK, IGL, CD3, CD14 and CD56) gating, after diagnostic phenotyping of fresh material, using the same panel and a EuroFlow B lymphoid screening tube. Sensitivity of both techniques was at least 0.01% (1E-04). FCM was only considered positive if above 0.01%, whereas Q-PCR results were considered positive below quantifiable range (BQR) if borderline, above sensitivity, within Euro-MRD criteria for MRD positivity. BQR samples were separated based on the number of positive, triplicate samples. The objectives were to compare the two techniques and to determine their suitability for regular screening, with a view to pre-emptive treatment on molecular or phenotypic (MRD) relapse. Two patients were treated with Rituximab at MRD relapse, prior to clinical relapse, as proof of principle. Results: A total of 302 blood or bone marrow samples from 62 patients were quantified. Overall, 79% (42/53) of samples positive at or above 0.01% by PCR were also positive by FCM, compared to 29% (19/65) of those below 0.01%, but with at least 2 positive triplicates and virtually none of those with only 1 or no results above sensitivity (1%, 2/184). Quantification of the paired MRD results positive with PCR and/or FCM were significantly correlated (r2=0.74, P<0.0001). Amongst the 62 patients, 30 have relapsed and 19 have died. Nine relapsing patients (including one off protocol patient treated and monitored at initial and second MRD relapses) had sufficient MRD points to assess the capacity of PB Q-PCR or FCM to predict future clinical relapse sufficiently to justify pre-emptive treatment at MRD relapse. Clinical relapse was preceded by MRD relapse in 9/10 relapses by Q-PCR and 7/9 by FCM. Six of the 9 relapsing patients had achieved Q-PCR negativity in at least one PB sample. The mean latency for prediction by Q-PCR, when considering any increase in positivity to at least 2 positive triplicates as positive, was 11.3 months (range 1-24mths) and 5.4 months (0.5-11) when only results above 0.01% were considered positive. The equivalent latency by FCM was slightly shorter, at 6.5 months (0.5-21) Pre-emptive treatment of 2 patients at MRD relapse, prior to clinical relapse allowed re-establishment of molecular complete remission and a durable second remission in at least one with sufficient follow-up (Cf Fig.). Figure 1 Figure 1. Conclusion: Eight color flow cytometry is a promising alternative to classical clone-specific Q-PCR strategies in monitoring therapy in MCL, with an excellent correlation (29/31, 94%) for MRD levels of at least 0.1% and acceptable correlation at 0.01-0.1% (13/22, 59%). While less sensitive at very low levels on cryopreserved material, FCM may clarify the clinical relevance of low-level borderline positivity; however it remains to be determined prospectively which technique will have greater prognostic value in patient management. FCM sensitivity will be improved by prognostic testing of fresh whole blood or bone marrow, and this pilot data clearly justifies such studies. Finally, MRD relapse precedes clinical relapse by several months, justifying pre-emptive treatment, monitored by prospective FCM and IgH Q-PCR within clinical trials. Disclosures Dreyling: Roche: Honoraria, Research Funding.

scholarly journals Mantle Zone Cell Lymphomas. New Opportunities for Diagnosis and Treatment (Epidemiological Research)

2020 ◽  
Vol 9 (4) ◽  
pp. 261-265
Author(s):  
E. I. Kankumasheva ◽  
Ch. Kh. Valiakhmetova
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Molecular Genetic ◽  
Epidemiological Data ◽  
Patient Specific ◽  
High Dose ◽  
Rare Type ◽  
Genetic Characteristics ◽  
Mantle Cell

Introduction. Mantle cell lymphoma is a rare type of B-cell non-Hodgkin lymphoma. According to statistics the incidence of this disorder amounts to 2-3 per 100,000 people; this is about 6% of all non-Hodgkin lymphomas. It has been established that various molecular genetic characteristics of mantle cell lymphoma patients may present opportunities for a patient-specific approach to the disease prognosis and treatment strategy.Materials and methods. The paper presents a retrospective analysis of 45 mantle cell lymphoma patients treated at the GAUZ RKOD of the Ministry of Healthcare from 2015 until now. The data used in the analysis included clinical examination, lab panels, PET CT, tumour and bone marrow biopsy specimen cytology, histology and immunohistochemistry. We analysed the epidemiological data, the patients’ clinical presentation characteristics, treatment approaches, immediate and long-term outcomes.Results and discussion. We have established that the pathological process most frequently involves bone marrow (44%) and spleen (41%). The MIPI scores distribution was as follows: high in 14 (30%), medium in 20 (45%), low in 11 (41%). Ki67 was recorded at under 30% in four cases, in others it amounted to over 30%. In 2015–2017 patients were treated with the R-CHOP protocol with the following support with rituximab. PFS averaged at 20 months, 8 (17%) of patients remain in lasting remission (since 2015). In 2017 the R-BAC (high dose cytarabine for SCT candidates) and R-B (for the elderly and comorbid patients) became protocols of first line. Since 2018 eight patients have undergone auto-SCT (at the first late recurrence) as a treatment consolidation stage. As of now 13 patients have been examined in federal centres for del17p and the TP53 mutation.Conclusion. We have demonstrated the need for and the option of treatment depending on the results of molecular genetic testing of mantle cell lymphomas.

Quantitative assessment of molecular remission after high-dose therapy with autologous stem cell transplantation predicts long-term remission in mantle cell lymphoma

Blood ◽  
2006 ◽  
Vol 107 (6) ◽  
pp. 2271-2278 ◽  
Author(s):  
Christiane Pott ◽  
Carsten Schrader ◽  
Stefan Gesk ◽  
Lana Harder ◽  
Markus Tiemann ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Mantle Cell Lymphoma ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
High Dose ◽  
Negative Group ◽  
Molecular Remission ◽  
Positive Group ◽  
Mantle Cell

Abstract To evaluate the prognostic impact of minimal residual disease (MRD), quantitative real-time polymerase chain reaction (RQ-PCR) of clonal IGH rearrangements was performed in 29 patients with mantle cell lymphoma (MCL) treated with high-dose radiochemotherapy and autologous stem cell transplantation (ASCT). Fourteen of 27 patients evaluable for MRD after ASCT achieved complete clinical and molecular remission, whereas 13 patients had detectable MRD within the first year after ASCT. Molecular remission after ASCT was strongly predictive for improved outcome, with a median progression-free survival (PFS) of 92 months in the MRD-negative group compared with 21 months in the MRD-positive group (P < .001). Median overall survival (OS) was 44 months in the MRD-positive group and has not been reached in the MRD-negative group (P < .003). In multivariate analysis, molecular remission and bulky disease were independent prognostic factors for PFS (P = .001 and P = .021, respectively). While cyclophosphamide, doxorubicin, vincristine, prednisolone (CHOP)–like cytoreduction had only modest influence, ara-C–containing mobilization and myeloablative radiochemotherapy significantly reduced MRD. Quantitative MRD measured in the stem cell products of 27 patients was not predictive for molecular remission. We conclude that sequential quantitative monitoring of residual disease after ASCT is a powerful indicator for treatment outcome in MCL and defines subgroups of patients with a significantly different prognosis.

scholarly journals Rituximab/bendamustine and rituximab/cytarabine induction therapy for transplant-eligible mantle cell lymphoma

2020 ◽  
Vol 4 (5) ◽  
pp. 858-867 ◽  
Author(s):  
Reid W. Merryman ◽  
Natasha Edwin ◽  
Robert Redd ◽  
Jad Bsat ◽  
Matthew Chase ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Residual Disease ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Pooled Analysis ◽  
High Dose ◽  
Phase 2 ◽  
Mantle Cell ◽  
High Dose Cytarabine

Abstract The addition of high-dose cytarabine to rituximab/bendamustine (RB) induction could improve outcomes for transplant-eligible patients with mantle cell lymphoma (MCL). We conducted a pooled analysis of 2 phase 2 trials and an off-trial cohort each testing 3 cycles of RB and 3 cycles of rituximab/high-dose cytarabine (RC) followed by autologous stem cell transplantation (ASCT) among untreated, transplant-eligible patients with MCL. Dana-Farber Cancer Institute (DFCI) and Washington University in St. Louis (WUSTL) led separate phase 2 trials testing sequential and alternating cycles of RB/RC, respectively. Patients treated at DFCI with sequential RB/RC off trial were retrospectively identified. Minimal residual disease (MRD) was assessed in the DFCI trial. A total of 88 patients (23 DFCI trial, 18 WUSTL trial, and 47 off trial) received RB/RC; 92% of patients completed induction, and 84% underwent planned consolidative ASCT. Grade 3 or 4 adverse events among trial patients included lymphopenia (88%), thrombocytopenia (85%), neutropenia (83%), and febrile neutropenia (15%). There were no treatment-related deaths during induction and 2 following ASCT. Among 87 response-evaluable patients, the end-of-induction overall and complete response rates were 97% and 90%, respectively. After a median follow-up of 33 months, 3-year progression-free survival and overall survival were 83% and 92%, respectively. Patients undergoing MRD testing experienced prolonged MRD negativity after ASCT with emergence of MRD occurring in only 1 patient who subsequently relapsed. RB/RC followed by ASCT achieves high rates of durable remissions in transplant-eligible patients with MCL. These trials were registered at www.clinicaltrials.gov as #NCT01661881 (DFCI trial) and #NCT02728531 (WUSTL trial).

scholarly journals Comparative outcome of initial therapy for younger patients with mantle cell lymphoma: an analysis from the NCCN NHL Database

Blood ◽  
2012 ◽  
Vol 119 (9) ◽  
pp. 2093-2099 ◽  
Author(s):  
Ann S. LaCasce ◽  
Jonathan L. Vandergrift ◽  
Maria A. Rodriguez ◽  
Gregory A. Abel ◽  
Allison L. Crosby ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Initial Therapy ◽  
Outcome Data ◽  
High Dose ◽  
Stem Cell Rescue ◽  
Non Hodgkin Lymphoma ◽  
Mantle Cell ◽  
Cancer Network

AbstractFew randomized trials have compared therapies in mantle cell lymphoma (MCL), and the role of aggressive induction is unclear. The National Comprehensive Cancer Network (NCCN) Non-Hodgkin Lymphoma (NHL) Database, a prospective cohort study collecting clinical, treatment, and outcome data at 7 NCCN centers, provides a unique opportunity to compare the effectiveness of initial therapies in MCL. Patients younger than 65 diagnosed between 2000 and 2008 were included if they received RHCVAD (rituximab fractionated cyclophosphamide, vincristine, adriamycin, and dexamethasone), RCHOP+HDT/ASCR (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone + high-dose therapy/autologous stem cell rescue), RHCVAD+HDT/ASCR, or RCHOP. Clinical parameters were similar for patients treated with RHCVAD (n = 83, 50%), RCHOP+HDT/ASCR (n = 34, 20%), RCHOP (n = 29, 17%), or RHCVAD+HDT/ASCR (n = 21, 13%). Overall, 70 (42%) of the 167 patients progressed and 25 (15%) expired with a median follow-up of 33 months. There was no difference in progression-free survival (PFS) between aggressive regimens (P > .57), which all demonstrated superior PFS compared with RCHOP (P < .004). There was no difference in overall survival (OS) between the RHCVAD and RCHOP+HDT/ASCR (P = .98). RCHOP was inferior to RHCVAD and RCHOP+HDT/ASCR, which had similar PFS and OS. Despite aggressive regimens, the median PFS was 3 to 4 years. Future trials should focus on novel agents rather than comparing current approaches.

Update of a GITIL Cohort Study: Frontline High Dose Sequential Chemotherapy with Rituximab and Autologous Stem Cell Transplantation Induces a High Rate of Long-Term Remissions in Patients with Mantle Cell Lymphoma

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1282-1282 ◽  
Author(s):  
Sergio Cortelazzo ◽  
Michele Magni ◽  
Corrado Tarella ◽  
Michael Mian ◽  
Atto Billio ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Cohort Study ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
High Dose ◽  
Sequential Chemotherapy ◽  
Mantle Cell ◽  
Group 2 ◽  
Group 1

Abstract We updated a cohort study with the aim of evaluating if an up-front Rituximab supplemented high-dose sequential chemotherapy (R-HDS), supported by autologous bone marrow transplantation (ASCT) can induce log-term remissions in Mantle Cell Lymphoma (MCL), with an acceptable toxic profile. From 1997 to 2005, 77 consecutive MCL patients, <61 year old, considered suitable for ASCT in 11 Italian cancer centres were enrolled in this study (Group 1). Their clinical outcome was compared with that of 79 age-matched historic controls treated between 1978 and 1999 with standard-dose anthracyclin or fludarabine containing regimens (group 2). The majority of both groups had an advanced stage, bone marrow infiltration and >1 IPI risk factors, while >1 extranodal sites prevailed in Group 1 and a poor ECOG-PS in Group 2. After 2–3 cycles of either doxorubicin- or cisplatin-containing chemotherapy, Group 1 received R-HDS including: HD-cyclophosphamide (CTX) 7 gr/sqm and HD-Ara-C (2 g/sqm every 12 hours for 6 days), followed by HDS HD-melphalan (180 mg/sqm) and/or HD-mitoxantrone plus melphalan (60 and 180 mg/sqm) and ASCT. Rituximab (375 mg /sqm) was given for a total of 6 doses, twice after HD-CTX and HD-Ara-C, as in vivo purging before CD34+ cells harvest and twice after ASCT. Sixty-nine patients (90%) in Group 1 completed the planned program and a median number of 6.3 x 10^6 cells CD34+/kg were transplanted. In Group 2, 85% of patients received the planned chemotherapy. The CR rate was 86% in Group 1 and 35% in Group 2 and the treatment-related mortality was 1.3% and 0.8%, respectively. Moreover, in Group 1, 4 patient developed sMDS, and 4 died of solid tumors (n=3), or septic shock (n=1). After a median follow-up of 50 months (range 3–111) in Group 1 and 37 months (range 1–141) in Group 2, the rate of 1st CCR was 65% and 14%, respectively. The 5-year projected OS, EFS and DFS were 74%, 61% and 70%, in Group 1 and 31%, 14% and 25%, in Group 2, respectively. Cox multivariate analysis failed to identify within potential prognostic markers factors predictive for OS and EFS. In conclusion, R-HDS induces long-term remissions with a manageable toxicity in patients with newly diagnosed MCL. Studies comparing this program with other intensive regimens are needed for ascertaining the role of R-HDS in the treatment of this otherwise incurable disease.

Transplantation for mantle cell lymphoma: is it the right thing to do?

Hematology ◽  
2013 ◽  
Vol 2013 (1) ◽  
pp. 568-574 ◽  
Author(s):  
Michael E. Williams
Keyword(s):  
Mantle Cell Lymphoma ◽  
Randomized Clinical Trials ◽  
Cell Lymphoma ◽  
Treatment Plan ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
Initial Therapy ◽  
High Dose ◽  
Cell Death Pathway ◽  
Mantle Cell

Abstract Mantle cell lymphoma (MCL) is a unique subtype of non-Hodgkin lymphoma that is both biologically and clinically heterogeneous. A variety of biomarkers, the achievement of minimal residual disease negativity after initial therapy, and the MCL International Prognostic Index (MIPI) are associated with patient outcome, although none has as yet been used for routine treatment stratification. Given the lack of widely accepted and standardized treatment approaches, clinical trial enrollment should always be considered for the initial therapy of MCL. Outside of the trial setting, younger and transplantation-eligible patients with newly diagnosed MCL who require treatment should first be considered for a rituximab + a high-dose cytarabine–containing regimen, followed by autologous stem cell transplantation consolidation in first remission. Symptomatic elderly and nontransplantation-eligible individuals typically receive rituximab + bendamustine, or R-CHOP (rituximab + cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/prednisolone) followed by maintenance rituximab, the latter a treatment plan that has demonstrated extended response duration and survival. Promising early results for consolidation approaches with proteasome inhibitors and immunomodulatory drugs are now being tested in randomized clinical trials. The availability of highly active BCR signaling pathway inhibitors and cell death pathway modulation via BH3 mimetics, among other novel agents, promise to rapidly expand treatment options, change existing treatment paradigms, and further improve outcomes for MCL patients.

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