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AbstractMinimal residual disease (MRD) has emerged as an important prognostic maker in patients with multiple myeloma at different stages of their treatment. Moreover, it is being increasingly incorporated as an endpoint in various clinical trials. Since maintenance therapy is an integral part of myeloma treatment, especially in the upfront setting post autologous transplantation, it is imperative to understand the role of MRD testing in the maintenance stetting. This review aims to examine the utility and dynamics of MRD testing in order to elucidate its prognostic role and possible incorporation in clinical decision making processes. [ABSTRACT FROM AUTHOR]

Cytarabine-containing chemoimmunotherapy followed by autologous transplantation and rituximab maintenance achieves durable remissions for most patients with mantle cell lymphoma (MCL). However, patients with TP53-mutated disease have poor outcomes with standard approaches. We previously reported that allogeneic stem cell transplantation (alloSCT) achieved durable remissions in MCL, however follow-up among patients with TP53-mutated disease was limited. Here we report extended follow-up of the overall cohort (n = 36) and TP53-mutated subset (n = 13) (median follow-up 10.8 and 4.2 years, respectively). Estimated overall survival was 56% at 10 years for the overall cohort and 59% at 4 years for the TP53-mutated subset. Among patients with TP53-mutated disease, no relapses occurred beyond 6 months post-transplant. Survival after post-alloSCT disease relapse was poor (median 2.1 years). These data confirm that alloSCT can be curative in MCL, including patients with TP53-mutated disease, and should be considered for earlier utilization in this subgroup for whom conventional chemoimmunotherapy is ineffective. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) is a rare, B-cell non-Hodgkin's lymphoma with a highly heterogeneous presentation that ranges from an indolent disease to an extremely aggressive one. Several clinical and biological prognostic markers can assist in determining the aggressiveness of the disease. Such as MIPI, Ki-67, and TP53, NOTCH1, and CDKN2A mutations. While aggressive chemoimmunotherapy regimens combining rituximab and cytarabine, followed by autologous stem-cell transplantation yield the most promising results, this treatment is too toxic for older patients. Several lower-intensity regimens have shown efficacy in older patients with reduced toxicity profiles. However, older relapsed/refractory patients have an extremely poor outcome. In the last several years, there is a major trend toward chemotherapy-free regimens, targeted therapies such as BTK, BCL-2 and PI3K inhibitors, and immunotherapies such as lenalidomide and CAR-T, which can provide a promising strategy for older patients. Herein we review the current therapies for older MCL patients, chemotherapy regimens, targeted therapies, and immunotherapies. [ABSTRACT FROM AUTHOR]

Tandem ASCT has been suggested as a valid approach to improve the prognosis of patients with MM and HR cytogenetic. In this observational, retrospective study, 213 patients with newly diagnosed MM and HR cytogenetic in 35 hospitals from the Spanish Myeloma Group underwent single or tandem ASCT between January 2015 and December 2019 after induction with VTD/VRD. HR cytogenetic was defined as having ≥1 of the following: del17p, t(4;14), t(14;16) or gain 1q21. More patients in the tandem group had R-ISS 3 and >1 cytogenetic abnormality at diagnosis. With a median follow-up of 31 months (range, 10–82), PFS after single ASCT was 41 months versus 48 months with tandem ASCT (p = 0.33). PFS in patients with del17p undergoing single ASCT was 41 months, while 52% of patients undergoing tandem ASCT were alive and disease free at 48 months. In conclusion, tandem ASCT partly overcomes the bad prognosis of HR cytogenetic. [ABSTRACT FROM AUTHOR]

There is no established standard treatment for relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in patients who are not eligible to receive an intensive treatment. The combination of rituximab gemcitabine and oxaliplatin (R-GemOx) is widely used in this population but data are scarce. We retrospectively collected the data of 196 patients with R/R DLBCL treated with R-GemOx in two French centers over a period of 15 years. The median age of the population was 72 years (range, 24–89), 63% of the patients had an international prognostic index of 3 or higher and 57% were refractory to the last treatment. At the end of R-GemOx treatment, 33% of the patients obtained a complete response. The median progression-free survival (PFS) of the population was 5 months and the median overall survival (OS) was 10 months. Several factors were predictors of unfavorable survival: age over 75 years, international prognostic index of 2 or higher, refractory disease and de novo DLBCL. The median PFS and OS of the patients who obtained a complete response were 22 months and 40 months, respectively. The most significant toxicities were grade 3–4 hematological toxicities (31% of patients). Given its efficacy and tolerability, R-GemOx can be used in patients ineligible for intensive treatment and serve as a basis for new regimen combinations. [ABSTRACT FROM AUTHOR]

We evaluate the safety of bendamustine as a bridge to stem cell transplantation (SCT) in patients with relapsed/refractory lymphoma and residual disease after salvage therapy. Thirty-four subjects without complete responses (CR) received bendamustine 200 mg/m2/day for 2 days followed 14 days later by SCT. Sixteen subjects in partial remission (PR) with maximal FDG-PET SUVs ≤8 prior to bendamustine received autologous SCT, while 13 with suboptimal responses were allografted. Five subjects did not proceed to transplant. No bendamustine toxicities precluded transplantation and no detrimental effect on engraftment or early treatment-related mortality (TRM) was attributable to bendamustine. At 1 year, 75% of auto-recipients and 31% of allo-recipients were alive with CR. Two subjects in the autologous arm developed therapy-related myeloid neoplasia (t-MN). In conclusion, a bendamustine bridge to SCT can be administered without early toxicity to patients with suboptimal responses to salvage chemotherapy. However this approach may increase the risk of t-MN. (NCT02059239). Supplemental data for this article is available online at . [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (auto-SCT) is an established treatment option in patients with non-Hodgkin lymphoma (NHL). In this prospective multicenter study, the effect of infused blood graft cellular composition on post-transplant outcome was analyzed in 129 NHL patients. Higher graft CD34+ cell content (>2.5 × 106/kg) correlated with better progression-free survival (PFS) (p=.009) and overall survival (OS) (p=.004). Higher graft CD34+CD133+CD38– counts (>0.08 × 106/kg) were also linked with better PFS (p=.03) and OS (p=.004), and these survival benefits retained in multivariate analyses. Higher infused CD3+CD4+ cell count (>37 × 106/kg) predicted better PFS (p=.013) and OS (p=.007) in multivariate analysis. Autograft cellular composition seems to impact outcome in NHL patients. These observations regarding composition of optimal graft in autologous setting should be validated in an independent patient series or in a randomized study. [ABSTRACT FROM AUTHOR]

The treatment of classic Hodgkin lymphoma (HL) is a success in onco-hematology. Despite the high cure rate of HL with initial therapy, 5–10% of patients are primary refractory and 10–20% will eventually relapse. The standard treatment for these patients is salvage chemotherapy and autologous stem cell transplantation (ASCT). Only about half of these patients will benefit from this procedure. The prognosis of relapsed refractory (rr) HL has improved with the introduction of effective drugs. With these options available, identification of reliable risk factors is important to guide treatment over the course of disease. Different variables including performance status, anemia, B symptoms, laboratory abnormalities, treatment intensity before ASCT, response to therapy, and duration of remission, have been analyzed to determine risk for progression-free survival (PFS) and overall survival (OS) after ASCT. This review will discuss the publications analyzing these factors, the validated risk scores useful to identify patients at high risk of progression after ASCT, and will describe future perspectives. [ABSTRACT FROM AUTHOR]

The distinct clinical characteristics of patients at diagnosis of diffuse large B-cell lymphoma (DLBCL), who experience a late relapse compared with those who relapse early, require reappraisal in the era of R-CHOP. Data from the lymphoma registry of the Asan Medical Center between 2002 and 2015 were retrospectively reviewed. Among 846 DLBCL patients treated with first-line R-CHOP and achieved complete response, 169 (20%) relapsed, occurring late (>2 years) in 51 (6%). Compared with early relapses, late relapses were associated with a lower International Prognostic Index score (p=.001), lower incidence of B-symptoms (p=.004), lower lactate dehydrogenase (p=.001), lower stage (I–II; p=.001), and the median overall survival from relapse was significantly longer (2.4 vs. 1.0 years, p=.001). Patients with a late relapse who responded to salvage chemotherapy and received autologous stem-cell transplantation, had higher 5-year survival rate (55.4% vs. 20.2%). Time of relapse and LDH level were independent prognostic factors affecting survival. [ABSTRACT FROM AUTHOR]

Phase II data suggest a benefit to autotransplantation for aggressive T-cell non-Hodgkin lymphoma (T-NHL) in first remission; randomized trials have yet to validate this. We performed a retrospective analysis of aggressive T-NHL patients in the intergroup randomized consolidative autotransplant trial (SWOG 9704). Of the 370 enrolled, 40 had T-NHL: 12 were not randomized due to ineligibility (n = 1), choice (n = 2), or progression (n = 9), leaving 13 randomized to control and 15 to autologous stem cell transplantation (ASCT). Two ASCT patients refused transplant and one failed mobilization. The 5-year landmark PFS/OS estimates for ASCT vs. control groups were 40% vs. 38% (p =.56), and 40% vs. 45% (p =.98), respectively. No difference was seen based on IPI, or histologic subtype. Only 1/7 receiving BCNU-based therapy survived vs. 4/5 receiving TBI. Aggressive T-NHL autotransplanted in first remission did not appear to benefit from consolidative ASCT. This and the 30% who dropped out pre-randomization mostly to progression, suggests that improved induction regimens be developed. [ABSTRACT FROM AUTHOR]

The article discusses the role of plerixafor, a small bicyclam molecule CXCR4 antagonist, in patients with and non-Hodgkin B-cell lymphomas (B-NHL) and multiple myeloma (MM) who had failed the previous mobilization with granulocyte-colony stimulating factor (G-CSF). Topics discussed include remobilization of autologous hematopoietic stem cells, cytotoxic chemotherapy, and hematopoietic recovery.

To evaluate the role of high-dose melphalan plus autologous stem-cell transplantation (ASCT) as consolidation therapy for patients with newly diagnosed multiple myeloma (NDMM) in the era of novel agents, we undertook this meta-analysis. Medline, Embase, the Cochrane controlled trials register, the SCI, ASH, EHA, and ASCO were searched for clinical trials including high-dose chemotherapy plus ASCT for patients with NDMM. Finally, we identified four RCTs of ASCT versus novel agents based consolidations, and 10 single-arm prospective trials of ASCT alone. Pooled analysis indicated that response quality improved further after ASCT in the era of novel agents (≥CR rates of 13% pre-ASCT versus 29% post-ASCT, p =.003). When compared to novel agents containing consolidation regimens, high-dose chemotherapy plus ASCT significantly improved progression-free survival (PFS) (HR =0.56, p <.001). No significant difference in overall survival (OS) was found between them (HR =0.66, p =.22). Of note, subgroup analysis indicated that ASCT could significantly improve OS (HR =0.49, p =.0004) when compared to alkylating agent-based regimens plus lenalidomide consolidation. In summary, response quality and PFS improved further over ASCT in the era of novel agents. ASCT could improve survival than alkylating agent-based regimens plus lenalidomide consolidations for patients with NDMM. [ABSTRACT FROM AUTHOR]

Clinical heterogeneity and predictors of outcome in primary autoimmune hemolytic anemia: a GIMEMA study of 308 patients. Cold agglutinin mediated autoimmune hemolytic anemia is rare condition, constituting approximately the 15% of all autoimmune hemolytic anemia [[4]]. Autologous peripheral blood stem cell harvest and transplant in a patient with cold agglutinin disease secondary to lymphoma. Cold agglutinin mediated autoimmune hemolytic anemia is an uncommon disorder characterized by the presence of cold agglutinins and it is associated with clinical symptoms caused by anemia and agglutination of red blood cells (RBC) in the coolest and peripheral parts of the body causing circulatory disorders such as acrocyanosis, Raynaud-like symptoms and livedo reticularis [[1]]. [Extracted from the article]

Although chemoimmunotherapy improves outcomes for patients with follicular lymphoma (FL), approximately 20% of patients experience early disease progression within two years of treatment and subsequently poor median survival. We conducted a retrospective study to evaluate survival rates of patients with early relapse who were treated with or without autologous transplantation. Of 517 patients with FL and who received chemoimmunotherapy, 152 relapsed and survived a minimum of four months after progression, including 84 (55.3%) with early relapse ≤2 years following initial therapy and 68 (44.7%) with later relapse. Five-year survival was superior for patients who received autologous transplantation compared to non-transplanted patients within the early relapse group (85.4% vs 57.9%, p = .001), but not within the late relapse group (p = .64). Given the limitations of a retrospective study, our study may suggest that the use of autologous transplantation for FL patients who relapse within two years of initial chemoimmunotherapy is associated with improved survival. [ABSTRACT FROM AUTHOR]

In this phase 1 study, we tested increasing doses of total marrow irradiation (TMI) in addition to standard intravenous melphalan at 200 mg/m2 (Mel200) in the conditioning regimen prior to autologous stem cell transplant (ASCT) for multiple myeloma (NCT02043847). Twelve patients aged 18-75 with relapsed myeloma were enrolled in the study and received Mel200 and TMI 3 Gy (n = 3), 6 Gy (n = 3), or 9 Gy (n = 6) prior to transplant. There were no grade 4 extra-hematologic toxicities and a maximum tolerated dose was not reached. Median time to neutrophil and platelet engraftment was 11 and 13 d, respectively. At day 90, 73% of patients were in CR or VGPR. Median progression free survival (PFS) was 449 d and median overall survival (OS) was 966 d. We conclude that TMI at a dose of 9 Gy can be safely combined with Mel200 in therapeutic regimens for autologous transplant. Initial clinical results will prompt a phase 2 study. [ABSTRACT FROM AUTHOR]

In this retrospective study, we quantified the hematogone (normal B-lineage precursor) population by flow cytometric immunophenotyping in post-transplant bone marrow biopsy specimens from adult patients who received an autologous stem cell transplant for either plasma cell myeloma (n = 57) or diffuse large B-cell lymphoma (n = 73). The majority of patients (80%) had <5% marrow hematogones post-transplant. Extreme (>10%) hematogone percentages were quite rare, seen in only four patients, and were not associated with disease progression. There was a positive association between the post-transplant day and hematogone percentage within the first year after transplant, and a negative association thereafter. Plasma cell myeloma patients with ≥5% hematogones in any post-transplant flow cytometry study had a worse overall survival as did plasma cell myeloma patients with increased hematogones (as defined by percentile) at 100 days post-transplant. These findings require further study, ideally in a prospective study design. [ABSTRACT FROM AUTHOR]

Plerixafor, although costly, is added to mobilizing chemotherapy and G-CSF to overcome poor stem cell mobilization. We demonstrate that it can be safely administered mostly once as a single dose in preemptive and rescue settings, leading to apheresis yields of >2 and >4×106CD34 + cells/kg body weight (bw) in 83% and 48%, respectively. Of note, 35/46 (76%) patients showed a substantial benefit with increased peripheral blood (PB) CD34 + cells prior to apheresis (8.84 vs. 1.72/μl,p < .001), and 5-fold increased CD34 + cells collected per single apheresis (2.25 vs. 0.43 × 106CD34+/kg bw, respectively,p < .001). Patients profiting most (76%) vs. less (24%) had >5 vs. <5/μl PB CD34 + cells before plerixafor application, respectively, thus careful patient selection in the latter group is advised. To the best of our knowledge, this is the first report demonstrating that favorable apheresis results can be obtained using this cost-efficient, single fixed-dose plerixafor schedule. [ABSTRACT FROM PUBLISHER]

Brachial plexopathy, also known as Parsonage-Turner syndrome or neuralgic amyotrophy, is an uncommon peripheral neuropathy characterized by acute-onset, dull, severe pain followed by limb weakness and muscle atrophy. Nevertheless, one should look for indirect, subtle findings, best identified in T2-weighted images, such as long-segment enlargement of one or more portions of the plexus, high-intensity signal in the peripheral margins of surrounding muscle groups and muscle atrophy [[17]]. EMG findings characteristic of the syndrome include low sensory nerve action potential, low compound muscle action potential amplitudes and denervation [[17]]. [Extracted from the article]

An introduction is presented in which the editor discusses the role of chemotherapy in high dose in patients with multiple myeloma.

Optimal frontline treatment in younger high tumor-burden risk follicular lymphoma patients remains a challenge given the reduced efficacy of standard immunochemotherapy (R-CHOP) in widespread disease and unclear role of intensive induction. The retrospective non-randomized pair-matched (1:3) analysis compared 48 intermediate/high Follicular Lymphoma International Prognostic Index (FLIPI) patients receiving intensive rituximab sequential chemotherapy (R-SQ) with 144 random controls (R-CHOP) matched for age, FLIPI score, and maintenance delivery. Complete response rates were 91.7% and 74.1%, respectively (p = .038). After a median follow-up of 8.8 (R-SQ) and 6.5 years (R-CHOP), 5-year time to treatment failure, progression-free survival, and overall survival were 80.9%, 83.2%, and 100% and 57.5%, 60.3%, and 92.1% (p = .0044;p = .0047;p = .22), respectively. Intensive treatment was accompanied by higher acute hematologic toxicity and infections, comparable non-hematologic toxicity, and incidence of secondary malignancies. Intensive induction demonstrates superior long-term disease control compared to R-CHOP, with higher acute hematologic toxicity, but without acute treatment-related mortality. Further studies are needed to define ultra-high-risk FL patients benefiting most from treatment intensity. [ABSTRACT FROM PUBLISHER]

The impact of the addition of rituximab to salvage chemotherapy prior to autologous stem cell transplant (ASCT) was evaluated in a retrospective subgroup analysis of NCIC CTG LY.12. Among 414 patients who relapsed following R-CHOP, 96 received salvage chemotherapy alone [R − cohort]; and 318 received rituximab with chemotherapy [R + cohort] following a protocol amendment. The R−cohort had a higher proportion of patients with PS ≥2 and relapse <1 year after R-CHOP. The response rate (45.6% vs. 25.0%,p = 0.0003), CR/CRu (15.7% vs. 4.2%,p = 0.003) and transplantation rate (51.9% vs. 31.3%,p = 0.0004) was higher in the R + cohort. Event-free (27% vs. 22%,p = 0.0954) and overall survival at four years (43% vs. 31%;p = 0.045) were greater in the R + cohort when the patients with best response SD/PD to R-CHOP were excluded. Addition of rituximab to salvage therapy before ASCT appears to improve the response rate, transplantation rate, and overall survival in patients with CD20+ lymphoma who responded to R-CHOP. [ABSTRACT FROM PUBLISHER]

High-dose therapy (HDT) followed by autologous stem cell transplant (ASCT) is the standard treatment for relapsed or refractory non-Hodgkin and Hodgkin lymphoma. Until recently, carmustine, etoposide, cytarabine and melphalan (BEAM) was the most commonly used conditioning regimen in this setting, given its acceptable efficacy and tolerability. Despite reasonable success with BEAM, carmustine is associated with a number of acute and late toxicities. Moreover, recent supply and cost issues for this agent have created an urgent need for alternative conditioning regimens. As such, etoposide and melphalan (VP16/MEL) or busulfan, cyclophosphamide, and etoposide (BuCyE) are currently being used with limited success. A number of novel conditioning regimens that replace carmustine with other agents are under investigation, which may provide effective alternatives to BEAM. In considering novel agents to replace carmustine, bendamustine may provide the best alternative, as demonstrated by the results of a number of phase II, multicenter, controlled studies. [ABSTRACT FROM PUBLISHER]

Limited data is available about the factors affecting early immune recovery or its clinical significance after autologous stem cell transplantation (auto-SCT). We prospectively analyzed factors affecting early immune recovery and outcome among 72 non-Hodgkin lymphoma (NHL) patients. Absolute lymphocyte count 15 d after auto-SCT (ALC-15) ≥ 0.5 × 109/L was associated with the use of plerixafor (p = 0.004), the number of CD34+cells (p = 0.015), and CD34+CD38−cells (p = 0.005) in the grafts. ALC-15 ≥ 0.5 × 109/L was associated with improved overall survival (p = 0.021). In patients with aggressive histology, ALC-15 ≥ 0.5 × 109/L was beneficial in regard to both progression-free survival (p = 0.015) and overall survival (p = 0.002). Early immune recovery seems to be important in transplanted patients with NHL and, therefore, an easy and affordable method for disease-related risk analysis. Patients with aggressive histology and slow immune recovery may need additional post-transplant treatment. [ABSTRACT FROM AUTHOR]

Only 50% of patients with relapsed Hodgkin lymphoma (HL) can be cured with intensive induction chemotherapy, followed by high-dose chemotherapy (HDCT) and autologous stem cell transplant (ASCT). Based on the results of the HDR2 trial two courses of DHAP and subsequent HDCT/ASCT are the current standard of care in relapsed HL. In order to assess the prognostic relevance of DHAP dose density, we performed a retrospective multivariate analysis of the HDR2 trial (N = 266). In addition to four risk factors (early or multiple relapse, stage IV disease or anemia at relapse, and grade IV hematotoxicity during the first cycle of DHAP) a delayed start of the second cycle of DHAP > day 22 predicted a significantly poorer progression-free survival (PFS,p = 0.0356) and overall survival (OS,p = 0.0025). In conclusion, our analysis strongly suggests that dose density of DHAP has a relevant impact on the outcome of relapsed HL patients. [ABSTRACT FROM PUBLISHER]

The authors comment on a study by M. Manna and colleagues which suggested the important role for high-dose therapy and autologous transplants in patients with high-risk follicular lymphoma. Topics include comparison of patients undergoing stem cell transplant early in the course of their disease to those who did not receive a transplant, risk of novel conventional chemotherapies and targeted treatments, and reason that quality of life may be favorably affected by autologous transplantation.

Few studies have evaluated the risk factors for hepatic sinusoidal obstructive syndrome (SOS) in patients with malignant lymphoma receiving autologous stem cell transplantation (ASCT). We retrospectively analyzed 132 malignant lymphoma patients who underwent ASCT. Intravenous busulfan-based conditioning regimens were used in 108 (81.8%) patients. The combination of heparin and ursodeoxycholic acid was used for prophylaxis of SOS. Hepatic SOS was developed in 10 (7.6%) patients at a median of 30 days post-ASCT. In nine (90.0%) patients, SOS was diagnosed after 20 days post-ASCT. Two patients developed severe SOS and eventually died from multiple organ failure. In multivariate analysis, the use of the busulfan-thiotepa conditioning regimen (p = 0.003) and a high pre-transplant serum ferritin level (≥ 950 ng/mL) (p = 0.003) were risk factors for hepatic SOS. The evaluation of pre-transplant serum ferritin may be helpful in determining the most appropriate conditioning regimen with a lower risk of SOS. [ABSTRACT FROM AUTHOR]

Extra-nodal NK/T lymphoma (ENKTL) is rare and more frequently encountered in East Asia. The role of high-dose therapy and autologous stem cell transplantation (HDT-ASCT) for ENKTL is unclear. Twenty-eight evaluable patients who had undergone HDT-ASCT in Europe from 2000–2009 were studied. The median age was 47 years and patients had received a median of two lines of prior therapy. Some 57% of patients were not in complete remission or beyond first complete remission at HDT-ASCT. The 1-year non-relapse mortality (NRM) was 11%; 2-year progression-free survival (PFS) and overall survival (OS) rates were 41% and 52%, respectively. Notably, the 2-year PFS and OS for those with stage III/IV disease were 33% and 40%, respectively, with no relapses beyond 1-year post-HDT-ASCT. This is the largest analysis of HDT-ASCT for patients with ENKTL reported from the Western hemisphere. Survival is comparable to East Asian cohorts and outcomes are encouraging for patients with advanced disease. [ABSTRACT FROM AUTHOR]

The article discusses a study demonstrating an adverse prognostic impact of amplification(1q)[+1q] of bad genes in newly diagnosed multiple myeloma (MM) patients undergoing induction therapy with proteasome inhibitors and/or immunomodulators followed by upfront autologous stem cell transplantation. It discusses cytogenetic abnormalities in MM, use of monoclonal antibodies and histone deacetylase inhibitors to negate impact of +1q and its candidate oncogenes including CKS1B, ANP32E, and BCL9.

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is difficult to treat, with limited therapeutic options. Review of prognostic indices, DLBCL genetic classification, previous rituximab exposure, interval from previous therapy, chemosensitivity to salvage therapy and response on imaging is helpful when deciding upon appropriate candidates for further therapy. For appropriately selected patients, the primary strategy is to obtain remission with salvage therapy and proceed to autologous stem cell transplant (ASCT). However, salvage therapy and transplant conditioning regimens are suboptimal, as are therapeutic options for patients who relapse following ASCT. Recent research highlights the ongoing difficulty in the treatment of relapsed/refractory DLBCL, and novel treatments are needed. [ABSTRACT FROM AUTHOR]

A bortezomib-containing regimen followed by high-dose therapy and autologous stem cell transplant (ASCT) is considered the standard of care for front-line therapy in younger patients with newly diagnosed multiple myeloma (MM). We analyzed the results of ASCT with an intravenous busulfan 9.6 mg/kg and melphalan 140 mg/m2 (ivBUMEL) preparative regimen in 47 patients with newly diagnosed MM who had received bortezomib-based combinations as pre-transplant induction. The overall response rate and complete response after transplant were 100% and 49%, respectively. With a median follow-up of 24.5 months, median overall survival and progression-free survival have not been reached. Mucositis and febrile neutropenia were the most frequent toxicities observed. No case of sinusoidal obstruction syndrome was observed and there was no transplant-related mortality. These results suggest that front-line induction therapy with a bortezomib-based combination followed by ASCT with ivBUMEL is an effective and well-tolerated therapeutic approach for transplant eligible patients with MM. [ABSTRACT FROM AUTHOR]

Mantle cell lymphoma (MCL) remains incurable with conventional chemotherapy without consensus on the optimal initial treatment. We examined our single center experience with frontline therapy for patients with MCL in consecutive cases diagnosed 1995-2011. Among 81 patients, median age was 59 (28% were ≥ 65 years of age), 95% had stage III/IV disease and 54% had a low risk MCL International Prognostic Index score. Thirty-five percent ( n = 28) received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) and 65% received R-HCVAD (rituximab, hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate/cytarabine; n = 53). Forty-one patients were consolidated with autologous stem cell transplant (ASCT). There were no significant differences in 2-year survival for R-CHOP versus R-HCVAD ( p = 0.10) or for ASCT versus observation ( p = 0.06). After controlling for clinical factors, R-HCVAD followed by ASCT was associated with superior progression-free survival (hazard ratio 0.26, 95% confidence interval 0.09-0.75). [ABSTRACT FROM AUTHOR]

The prognosis for patients with central nervous system (CNS) involvement by recurrent or refractory diffuse large B-cell lymphoma is poor, with overall survival (OS) of 4-10 months. High-dose chemotherapy (HDC) and autologous stem cell transplant (ASCT) is a potential treatment alternative. We reviewed patients with recurrent primary (PCNSL) or secondary (SCNSL) CNS lymphoma referred for consolidation HDC-ASCT utilizing thiotepa, busulfan and cyclophosphamide (TBC). Among the 17 patients included, all had achieved a complete remission after salvage induction chemotherapy, which incorporated methotrexate in 82% of patients. Two patients failed stem-cell harvesting and 15 (88%) underwent transplant. The estimated 3-year progression-free survival (PFS) and OS were both 93% (95% confidence interval 61-99%). Median PFS and OS were not reached. There was no transplant-related mortality. These results confirm the benefit of TBC followed by ASCT in select patients with recurrent PCNSL and suggest a potential role for the regimen in those with SCNSL. Further investigation is warranted. [ABSTRACT FROM AUTHOR]

The article discusses a feasibility study and treatment outcome of a conditioning regimen with BCNU, etoposide, cytarabine and melphalan plus amifostine (BEAMaM) for autologous stem cell transplant (ASCT) outpatients with lymphoma. Topics include a list of inclusion criteria for the study, the experimental design, and a discussion of the study results, such as rehospitalization rates, severe mucositis in individuals receiving BEAM, and quality of life (QOL).

In this article the authors discuss the role of autologous stem cell transplant in helping multiple myeloma (MM) patients with extramedullary plasmacytoma (EMPs) overcome a poor prognosis. He cites several studies demonstrating the long-term outcomes in patients with MM without extramedullary involvement versus those with EMPs, such as Wu et al. in a 2009 issue of "Leukemia & Lymphoma," and discusses prognostic factors for progression-free survival (PFS) and overall survival (OS).

Hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone/methotrexate, cytarabine (Hyper-CVAD) chemotherapy exerts deleterious effects on peripheral blood stem cell (PBSC) mobilization. We retrospectively reviewed the use of plerixafor to salvage mobilization in 18 Hyper-CVAD treated patients who initially mobilized poorly with chemotherapy and granulocyte colony stimulating factor (G-CSF). After plerixafor administration the median peripheral blood (PB) CD34 + count rose from 3.74/μL (0-17/μL) to 6.85/μL (0-47.2/μL). The patients collected a median of 1.64 (0.21-5.56) × 106 CD34 + cells/kg with a median number of 3 (1-4) doses in the same collection cycle, and 11 patients reached the 2.0 × 106 CD34 + cells/kg minimum required for transplant. Six patients were remobilized later with G-CSF and plerixafor, and three additional patients reached this goal. For these 14 patients the median number of doses of plerixafor required to reach 2.0 × 106 CD34 + cells/kg was 3 (range 1-4). In conclusion, plerixafor can be utilized successfully in many cases to overcome the effects of Hyper-CVAD on PBSC mobilization. [ABSTRACT FROM AUTHOR]

We evaluated the predictive value of [18F]fluoro-2-deoxy- d-glucose positron emission tomography (FDG-PET) for clinical outcome such as progression-free survival (PFS) and overall survival (OS) in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) prior to and after autologous stem cell transplant (ASCT). FDG-PET/computed tomography (CT) was performed in 39 consecutive patients with relapsed/refractory DLBCL scheduled for ASCT. The median follow-up of surviving patients was 3 years (range 19-66 months). Both pre- and post-ASCT, FDG-PET findings were strongly correlated with PFS and OS ( p < 0.005). The 2-year PFS estimates for FDG-negative versus -positive patients were 84.8% vs. 36.8% (pre-) and 81.1% vs. 13.3% (post-). The 2-year OS estimates in these groups were 95.5% vs. 68.3% (pre-) and 92.7% vs. 57.1% (post-). Patients were classified into three groups according to FDG-PET results before and after ASCT. The median PFS was significantly lower in the +/+ group (13.0 months) as compared with the +/− group (31.0 months, p = 0.021) and the −/− group ( p = 0.000). The regression model showed that the predictive value of FDG-PET before ASCT owed its significance to a very high hazard ratio between patients with positive and negative imaging ( p < 0.01). FDG-PET prior to and following ASCT in patients with relapsed or refractory DLBCL contains prognostic information on long-term clinical outcome. [ABSTRACT FROM AUTHOR]

Granulocyte-colony stimulating factors (G-CSFs) enhance bone marrow (BM) recovery after autologous stem cell transplant (ASCT) in patients with lymphoma and myeloma. Few publications exist that discuss the use of filgrastim biosimilars after ASCT. We conducted a single-center retrospective study in patients with lymphoma and myeloma treated at Brest Hospital to assess the cost reductions related to and the efficiency and safety of filgrastim biosimilars. We identified 65 patients with lymphoma or myeloma treated with filgrastim biosimilars for ASCT and compared 19 parameters of these patients, including BM recovery, side effects, infectious complications and treatment costs, with published historical data on a cohort of 50 patients treated with classic filgrastim. We observed a significant reduction of G-CSF costs in both groups but did not observe a change in total hospitalization costs (representing less than 2% of the costs) between groups. Additionally, we did not observe differences between the two groups in BM recovery, infectious complications, side effects or the other studied parameters. In this retrospective study, the absence of differences between groups after ASCT in lymphoma and myeloma led us to believe that these drugs could be safely and effectively used for such indications without a significant impact on hospitalization costs. A prospective study should be conducted to confirm our results. [ABSTRACT FROM AUTHOR]

There are no uniform guidelines for the treatment of relapsed refractory multiple myeloma (MM), however autologous stem cell transplant (SCT) remains an important treatment modality. Although a number of modifications to high dose melphalan (HDM) conditioning have been evaluated, improvement in overall survival has not been demonstrated. We now report our experience of 23 patients with heavily pretreated MM (median lines of prior treatment 3 [range 1-6]) who underwent SCT with bortezomib and high dose melphalan (BorHDM). The overall response rate (at least partial response [PR]) was 65.4%. Median overall survival (OS) was 24 months. A subset of patients who relapsed ≤ 12 months after initial SCT had significantly longer OS after BorHDM SCT compared to a historical control group who received HDM conditioning alone (14.5 vs. 8 months, respectively, p = 0.011). In summary, BorHDM SCT produces very good response rates in heavily pretreated MM, and may increase survival in the salvage setting in patients who relapse early after initial SCT. We propose that its use should be explored as part of a tandem approach in patients undergoing initial SCT who are at high risk of early relapse. [ABSTRACT FROM AUTHOR]

BEACOPP (bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone) escalated is the preferred upfront Hodgkin lymphoma (HL) treatment in a number of countries. Upon failure, high-dose chemotherapy with autologous stem cell support (HDT/ASCT) is performed, but its effectiveness has not been verified in this setting. We analyzed all Swiss cases of chemosensitive HL autografted after failure of BEACOPP escalated ( n = 22) and compared outcomes with 22 cases of HDT/ASCT following frontline ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) failure. Five-year progression-free survival (PFS) was 76% for ABVD and 42% for BEACOPP escalated ( p = 0.029). Two- and 5-year overall survival (OS) was 90% and 71% for ABVD and 72% and 65% for BEACOPP escalated, respectively ( p = not significant). Three patients in the ABVD and four in the BEACOPP escalated groups underwent allotransplant for relapse after HDT/ASCT. Grade 3-4 toxicities were comparable in both groups. Three cases of therapy-related myelodysplastic syndrome/acute myeloid leukemia (t-MDS/t-AML) were recorded in the BEACOPP escalated group. The acceptable PFS and OS of chemosensitive patients with HL autografted after failure of upfront BEACOPP escalated seem to justify this approach. [ABSTRACT FROM AUTHOR]

Published studies have provided conflicting results regarding the curative potential of high dose chemotherapy and autologous stem cell transplant (HDT/ASCT) for follicular lymphoma (FL). Our objectives were to evaluate the long-term event-free (EFS) and overall (OS) survival rates following ASCT for FL, and to identify predictors of improved outcome. We conducted a retrospective analysis of the first 100 consecutive patients with relapsed or refractory FL treated with HDT/ASCT in Calgary from 1993 to 2008. With a median follow-up of 65 months (range 16-178) post-ASCT, 5-year EFS and OS rates were 56% (95% confidence interval [CI] 46-66%) and 70% (95% CI 61-79%), respectively. A plateau on the EFS curve is evident starting 6 years post-ASCT. Also, the EFS post-ASCT was markedly longer than the 12-month median EFS from last therapy prior to ASCT ( p < 0.0001). Failure of rituximab pre-ASCT was not associated with EFS or OS. Severe toxicities included two early treatment-related deaths, and four late deaths from secondary leukemia. Independent predictors of EFS and OS in multivariate analysis were rituximab therapy within 6 months of ASCT, chemosensitivity and FLIPI (FL International Prognostic Index) score 0-1. In conclusion, our data suggest that over 50% of patients with relapsed/refractory FL who have failed 1-2 prior chemotherapy regimens achieve long-term EFS following HDT/ASCT. [ABSTRACT FROM AUTHOR]

This retrospective study evaluated the secondary clinical risk score at relapse, the prognostic significance of pre-transplant positron emission tomography (PET), and complete remission (CR) assessed by computed tomography (CT) after salvage chemotherapy before autologous stem cell transplant (ASCT) in 76 patients with relapsed/refractory Hodgkin lymphoma (HL). Median follow-up after ASCT was 23 months. Overall 11/20 PET-positive and 14/56 PET-negative patients relapsed after ASCT. In univariate analysis, only PET negativity before ASCT was significantly associated with better 2-year progression-free survival (PFS) (72.7 ± 6.3%% vs. 36.1 ± 11.6%%, p == 0.01) and 2-year overall survival (OS) (90.3 ± 4.1%% vs. 61.4 ± 11.6%%, p == 0.009). Other factors were not significant. In multivariate analysis, none of the evaluated factors were significant for PFS and OS. However, positive pre-transplant PET identified a population with worse PFS and OS at least in univariate analysis. [ABSTRACT FROM AUTHOR]

For patients with relapsed or refractory multiple myeloma (MM) treated with a prior high-dose therapy (HDT) followed by autologous peripheral blood stem cell transplantation (PBSCT), the reapplication of HDT is a widely used salvage strategy. In this retrospective study, we report on 55 patients who were treated with salvage HDT at our institution. The conditioning regimen consisted of melphalan 200  mg/m2 (27%%), melphalan 140  mg/m2 and busulfan 12  mg/kg body weight (40%%), or melphalan 200  mg/m2 and bortezomib 1.3  mg/m2 (33%%). Treatment-related mortality was 5%% and response rates were as follows: 9%% complete remission, 9%% very good partial remission, 56%% partial remission, 11%% minimal response ++ stable disease, and 4%% progressive disease (5%% not assessable). Toxicity was moderate and the median event-free (EFS) and overall survival (OS) were 14 months and 52 months, respectively. The different conditioning regimens did not result in differences in terms of remission rates, EFS and OS, or toxicity. In multivariate analysis a duration of remission of more than 12 months after the first transplant was the only predictive factor for both EFS ( p < 0.0001) and OS ( p  ==  0.0001). In conclusion, salvage HDT followed by autologous PBSCT is an effective treatment option for patients with relapsed or refractory MM, while patients with an early relapse after their first transplant do not benefit from this treatment modality. [ABSTRACT FROM AUTHOR]

Evidence of long-term response to lenalidomide in heavily pretreated patients with multiple myeloma is lacking. This study sought to assess whether long-term responders exist, long-term responders' characteristics, and predictive factors of a long-term response. One hundred and four patients with multiple myeloma treated with lenalidomide and dexamethasone after ≥≥2 therapy lines (median, 3) were analyzed. Long-term response was defined as at least a partial response (≥≥PR) lasting ≥≥12 months. The overall response rate was 73%%, and 80.3%% of the responses were achieved within 5 months. The median response was 14.3 months. Patients evaluable for long-term response numbered 87, and a total of 47%% were long-term responders. Compared to non-long-term responders, long-term responders had better overall survival, less light-chain multiple myeloma, and higher incidence of t(11;14). Previous allogeneic transplant (alloSCT) and the response quality predicted a long-term response. In conclusion, patients treated with lenalidomide can become long-term responders; alloSCT and response quality predict long-term response. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy for the management of immunoglobulin light chain amyloidosis remains an effective and viable treatment technique for selected patients with this disorder. We reviewed the medical records of 434 patients uniformly treated with high-dose chemotherapy and autologous stem cell transplant at Mayo Clinic, Rochester, Minnesota, between 8 March 1996 and 13 April 2010. Outcomes, engraftment, and predictors of early mortality were reviewed. Median survival has not been reached for the patients with a complete response, is 107 months for those with a partial response, and is 32 months for patients with no response ( p < 0.001). The only predictor of survival was cardiac stage ( p < 0.001). The hematologic response rate is predictive for organ response rates. Both hematologic and organ responses are associated with improved survival. [ABSTRACT FROM AUTHOR]

High-dose chemotherapy followed by autologous stem cell transplant (ASCT) leads to durable remissions in approximately half of patients with chemosensitive relapsed or refractory aggressive lymphomas; however, many will relapse despite ASCT secondary to persistent minimal residual disease (MRD) or malignant graft contamination. Post-transplant rituximab may eradicate MRD. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) might enhance the efficacy of rituximab by augmenting antibody-dependent cellular cytotoxicity (ADCC). We hypothesized that given together, rituximab, GM-CSF, and IL-2 might eradicate MRD and improve event-free survival following ASCT. Forty-six patients with relapsed non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) were enrolled. Stem cells were mobilized with G-CSF and GM-CSF following chemotherapy. Following BEAM conditioning, patients received GM-CSF until neutrophil engraftment. Between days + 30 and + 120, patients received one dose of rituximab 375 mg/m2 (cycle 1), followed by three cycles of GM-CSF 250 μg/m2/day SQ days 1–5, IL-2 1.5 × 106 IU/m2/day SQ days 6–12, and rituximab 375 mg/m2 IV day 9, repeated every 21 days. Thirty-eight patients were eligible for post-ASCT immunotherapy. Nine patients completed 1–2 cycles and 21 completed 3–4 cycles; eight patients did not receive post-ASCT immunotherapy. Grade 3–4 neutropenia and grade 3 thrombocytopenia were observed. With a median follow-up of 30 months, the estimated 5-year OS and EFS for all patients eligible for immunotherapy are 65% and 45%, respectively. Post-ASCT immunomodulation with rituximab, IL-2, and GM-CSF was feasible and safe, but not all patients were able to continue on to post-ASCT immunotherapy. [ABSTRACT FROM AUTHOR]

The introduction of high-dose (HD) chemotherapy (CT) and autologous stem cell (ASCT) or bone marrow transplant (ABMT) in the last two decades has improved the prognosis of patients with refractory or relapsed Hodgkin lymphoma (HL) over conventional-dose salvage CT. To evaluate the outcome of adult patients with HL treated with HD CT and ASCT or ABMT after failure or relapse from first-line treatment with CT ± radiotherapy, we report the results of a retrospective analysis in 82 consecutive patients given HD CT and autologous transplant as second-line therapy between October 1984 and December 2006. Thirty-two patients were given sequential high-dose cytoreductive therapy while 50 received other conventional induction regimens. Seventy-three patients with chemoresponsive disease underwent the myeloablative phase, while eight patients had progressive disease during cytoreductive CT. After a median follow-up of 73 months, the 10-year progression-free survival (PFS) and overall survival (OS) were 57% and 51%, respectively. According to response to first-line treatment, PFS and OS were, respectively, 54% and 82% for patients with complete remission (CR) lasting 12 months or more; 49% and 51% for patients with CR less than 12 months; and 47% and 50% for patients who never achieved CR or progressed during first-line CT (induction failure). Response to cytoreductive CT significantly influenced outcome, with PFS and OS being, respectively, 56% and 68% vs. 44% and 47% ( p = 0.009) in patients in CR versus patients not in CR after induction therapy. Treatment was well tolerated, and therapy related mortality was only 3.7%. These long-term results confirm that HD CT and ASCT or ABMT was feasible, safe, and very effective. Therefore, this therapeutic strategy may represent an active salvage approach even in the unfavorable group of patients with induction failure. [ABSTRACT FROM AUTHOR]

High-dose melphalan therapy with peripheral blood stem cell (PBSC) transplantation is a standard treatment for younger patients with untreated multiple myeloma that results in high overall and complete response (CR) rates, and improved event-free and overall survival compared with standard chemotherapy alone. Induction therapy serves to reduce tumor burden prior to stem cell mobilization and thus must not adversely impact stem cell mobilization and harvesting, or engraftment following high dose therapy plus autologous stem cell transplantation. Bortezomib, an approved agent for the treatment of multiple myeloma patients who have received at least one prior therapy, is also being investigated in the frontline setting. Preclinical studies have demonstrated that bortezomib has no toxic effects on stem cells, megakaryocytes or neutrophil precursors, and causes only transient and reversible thrombocytopenia and neutropenia. Clinical studies with bortezomib-based induction regimens have demonstrated no adverse impact on PBSC harvest numbers nor on their quality as defined by engraftment times. These regimens appear to be well tolerated and highly active as induction therapy, with high response rates and consistently high CR rates. Randomized phase 3 studies comparing bortezomib-based regimens with current standard induction therapies are ongoing. [ABSTRACT FROM AUTHOR]

The risk for opportunistic infections is correlated with low CD4+ T lymphocyte counts in patients with HIV. We performed a retrospective analysis in 54 patients with multiple myeloma undergoing high-dose melphalan chemotherapy + autologous peripheral blood stem cell transplantation to better define the value of routine control of CD4+ T lymphocyte counts in this important patient group. In 61% of our patients, CD4+ T lymphocyte counts after recovery from neutropenia were <200/µl and <100/µl in 24% (median = 181/µl). Overall survival, progression-free survival, response to antineoplastic therapy and frequency of post-transplant infections were not significantly different when patients with CD4+ T lymphocyte counts <200/µl and >200/µl were compared. However, overall survival was significantly shorter in the subgroup of 13 patients with very low CD4+ T lymphocyte counts (<100/µl) (P = 0.036). In 79.6% of all patients, at least one infection NCI-CTC grade II - IV developed within 100 days post-transplant. Opportunistic infections were rare. This analysis suggests that patients with CD4+ T lymphocyte counts < 100/µl may have a poorer prognosis. [ABSTRACT FROM AUTHOR]

Lymphoma was first described in 1862 and follicular lymphoma in 1925. Initially considered a benign disorder, and named Brill – Symmers disease after the authors of the original papers, it was rapidly recognized as a malignancy with a variable but often indolent course. Most of its clinical features were described by the early 1940s. Despite discussion about its cell of origin, and in contrast to many other lymphoma subtypes, follicular lymphoma could always be accurately recognized and diagnosed using light microscopy morphological features. B-cell origin was demonstrated in the 1970s and the important role of t(14;18) and bcl-2 gene rearrangement in the pathogenesis of follicular lymphoma was established shortly thereafter. The etiology of follicular lymphoma, the reason for marked geographic variation in its incidence, the role of alternative molecular pathways in its pathogenesis, and the cause for its variable clinical behavior all remain unknown. Several observations suggest an important role for the normal immune response in regulating the clinical behavior of follicular lymphoma. From the earliest descriptions, radiation therapy was shown to be very effective in follicular lymphoma, but not curative. Combination chemotherapy was tested in the 1970s, but despite high rates of response, there was only minimal impact on survival. Interferon combined with anthracycline based chemotherapy was the first treatment to improve survival, but was not widely adopted in the USA. Randomized studies have shown an impact of autologous transplantation on progression free survival. Allogeneic transplantation is a curative therapy, but is too toxic for widespread application. Targeted therapies, particularly rituximab have revolutionized the treatment of follicular lymphoma. A convergence of technological and biological advances will likely lead to further dramatic progress in the next decade. For the first time consistent improvements in survival of follicular lymphoma are reported. [ABSTRACT FROM AUTHOR]

Interestingly, although insurance type was a significant predictor of survival among patients that received non-transplant therapies, it did not affect survival amongst transplant recipients. Induction chemotherapy with at least three drugs (including bortezomib), followed by high-dose melphalan and autologous stem cell transplantation and maintenance therapy are considered standard of care for "transplant-eligible" MM patients. [Extracted from the article]