Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23–68 years). Median time from diagnosis to transplant was 7 months (3–79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9–144.7 months) and 73.8 months (95% C.I. 57.7–89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p?=?0.024), while OS was better with CR/VGPR post-ASCT (p?<?0.001) and lenalidomide maintenance therapy (p?=?0.009). PFS was affected by CR/VGPR pre-ASCT (p?=?0.021), CR/VGPR post-ASCT (p?<?0.001), and transplant in first remission (p?=?0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p?=?0.007) and CR/VGPR response post-ASCT (p?=?0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p?=?0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p?=?0.073). Conclusion: Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.     

Interim <Superscript>18</Superscript>F-FGD PET/CT may not predict the outcome in primary central nervous system lymphoma patients treated with sequential treatment with methotrexate and cytarabine

¹⁸F-fluoro-2-dexoy-D-glucose-positron emission tomography (PET)/computed tomography (CT) is a useful imaging technique for monitoring the treatment response in lymphoma cases. We investigated the value of interim brain PET/CT (I-PET/CT) for monitoring the response to intensive methotrexate-based chemotherapy in primary central nervous system lymphoma (PCNSL) patients with diffuse large B cell lymphoma (DLBCL). Of the 76 PCNSL patients treated with intensive methotrexate and cytarabine chemotherapy between September 2006 and December 2012, 66 patients with DLBCL were included in this study. The patient cohort of 66 individuals comprised 43 men and 23 women with a median age of 59 years (range, 17–75 years). During chemotherapy, 36 patients (54.5%) showed a negative metabolism on I-PET/CT, and 47 (71.2%) were negative on final (F) PET/CT. The baseline characteristics were similar between I-PET/CT-negative (n = 36) and I-PET/CT-positive patients (n = 30) except ECOG performance status. After a median follow-up of 27.5 months, there was no difference in the progression-free survival (PFS; P = 0.701) or overall survival (OS; P = 0.620) between the I-PET/CT-negative and I-PET/CT-positive groups. However, PFS in the F-PET/CT-negative group was significantly longer than that in the F-PET/CT-positive group (P < 0.001) without a significant difference in OS (P = 0.892). I-PET/CT may not predict the survival outcome of PCNSL patients with DLBCL treated with intensive methotrexate and cytarabine chemotherapy. Prospective trials are required to fully evaluate the role of I-PET/CT.     

The prognostic role of CD68 and FoxP3 expression in patients with primary central nervous system lymphoma

The prognostic role of CD68 and FoxP3 in primary central nervous system lymphoma (PCNSL) has not been evaluated. Thus, we examined the prognostic significance of CD68 and FoxP3 expression in tumor samples of 76 newly diagnosed immunocompetent PCNSL patients. All patients were treated initially with high-dose methotrexate (HD-MTX)-based chemotherapy, and 16 (21.1%) patients received upfront autologous stem cell transplantation (ASCT) consolidation. High expression of CD68 (>55 cells/high-power field) or FoxP3 (>15 cells/high-power field) was observed in 10 patients, respectively. High CD68 expression was associated with inferior overall survival (OS) and progression-free survival (PFS) in multivariate analysis (P = 0.023 and P = 0.021, respectively). In addition, we performed subgroup analysis based on upfront ASCT. High CD68 expression was also associated with inferior OS and PFS in multivariate analysis (P = 0.013 and P < 0.001, respectively) among patients who did not receive upfront ASCT (n = 60), but not in patients who received upfront ASCT. The expression of FoxP3 was not significantly associated with survival. Therefore, we identified a prognostic significance of high CD68 expression in PCNSL, which suggests a need for further clinical trials and biological studies on the role of PCNSL tumor microenvironment.     

Autologous stem cell transplantation (ASCT) in patients with mantle cell lymphoma: a retrospective study of the Spanish lymphoma group (GELTAMO)

Guidelines recommend autologous stem cell transplantation (ASCT) consolidation in first complete or partial response after regimens including rituximab (R) and high-dose AraC (HDAC), but its use beyond that response is questioned. We present a retrospective analysis of 268 patients with MCL who received ASCT. With a median follow-up for survival patients of 54 months, progression-free survival and overall survival for the whole series were 38 and 74 months, respectively, and for patients transplanted in first CR 49 and 97 months, respectively. Patients without CR before transplant were analyzed separately, those who achieved CR after transplantation had better PFS (48 vs 0.03 months, p < 0.001) and OS (92 vs 16 months, p < 0.001) than the remaining. In univariate analysis, first CR at transplant (p = 0.01) and prior rituximab (p = 0.02) were the variables associated with PFS. For OS, the same variables resulted significant (p = 0.03 and p < 0.001, respectively). In multivariate analysis, only the status at transplant (first CR) remained significant. This retrospective study concludes that ASCT consolidation in first CR induces high survival rates. In other stages of disease, the need of ASCT as consolidation may be questioned.     

Prognostic meaning of neutrophil to lymphocyte ratio (NLR) and lymphocyte to monocyte ration (LMR) in newly diagnosed Hodgkin lymphoma patients treated upfront with a PET-2 based strategy

Recent reports identify NLR (the ratio between absolute neutrophils counts, ANC, and absolute lymphocyte count, ALC), as predictor of progression-free survival (PFS) and overall survival (OS) in cancer patients. We retrospectively tested NLR and LMR (the ratio between absolute lymphocyte and monocyte counts) in newly diagnosed Hodgkin lymphoma (HL) patients treated upfront with a PET-2 risk-adapted strategy. NLR and LMR were calculated using records obtained from the complete blood count (CBC) from 180 newly diagnosed HL patients. PFS was evaluated accordingly to Kaplan-Meier method. Higher NLR was associated to advanced stage, increased absolute counts of neutrophils and reduced count of lymphocytes, and markers of systemic inflammation. After a median follow-up of 68 months, PFS at 60 months was 86.6% versus 70.1%, respectively, in patients with NLR?≥?6 or NLR?<?6. Predictors of PFS at 60 months were PET-2 scan (p?<?0.0001), NLR?≥?6.0 (p?=?0.02), LMR?<?2 (p?=?0.048), and ANC (p?=?0.0059) in univariate analysis, but only PET-2 was an independent predictor of PFS in multivariate analysis. Advanced-stage patients (N?=?119) were treated according to a PET-2 risk-adapted protocol, with an early switch to BEACOPP regimen in case of PET-2 positivity. Despite this strategy, patients with positive PET-2 still had an inferior outcome, with PFS at 60 months of 84.7% versus 40.1% (negative and positive PET-2 patients, respectively, p?<?0.0001). Independent predictors of PFS by multivariate analysis were PET-2 status and to a lesser extend NLR in advanced stage, while LMR maintained its significance in early stage. By focusing on PET-2 negative patients, we found that patients with NLR?≥?6.0 or LMR?<?2 had an inferior outcome compared to patients with both ratios above the cutoff (78.7 versus 91.9 months, p?=?0.01). We confirm NLR as predictor of PFS in HL patients independently from stage at diagnosis. Integration of PET-2 scan, NLR and LMR can result in a meaningful prognostic system that needs to be further validated in prospective series including patients treated upfront with PET-2 adapted-risk therapy.     

Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p?=?0.005), elevated lactate dehydrogenase ratio >1 (p?<?0.001), advanced Ann Arbor stage (p?=?0.002), and bulky disease (p?=?0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR]?=?1.967, 95 % confidence interval [CI]?=?1.399–2.765, p?<?0.001; OS, HR?=?2.445, 95 % CI?=?1.689–3.640, p?<?0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.     

Repeating of local therapy of distant metastases increases overall survival in patients with synchronous metastasized rectal cancer—a monocentric analysis

Purpose

The aim was to evaluate the outcome of treatment-naive patients with synchronous metastatic rectal cancer after chemotherapy with FOLFOXIRI followed by local therapeutic procedures of all tumor lesions as complete as possible.

Methods

We reviewed data of 30 patients with synchronous distant metastatic rectal cancer who underwent chemotherapy with FOLFOXIRI and subsequent local therapy in our institution.

Results

Median follow-up was 28 months (range: 8; 74). Cumulative overall survival (OS) and progression-free survival (PFS) was 93.3, 76.9, 55.6% and 46.2, 29.7, 29.7% after 1, 2, 4 years. Non-response to chemotherapy with FOLFOXIRI was associated with a highly significant decreased OS (p?<?0.0001). The consistent use of local ablative procedures led to a statistically significant increase in OS (p?<?0.0001), but not in PFS (p?=?0.635). Patients with ≤?4 distant metastases showed a better OS (p?=?0.033).

Conclusions

Response to intensified first-line chemotherapy with FOLFOXIRI, treatment of the primary rectal tumor, and repeated thorough local ablative procedures in patients with synchronous metastasized rectal cancer may lead to long-term survival, even in a subset of patients with unresectable disease at initial diagnosis.

     

Bendamustine and rituximab (BR) versus dexamethasone,rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia

The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients’ MYD88^L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p?=?0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p?=?0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p?=?0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p?=?0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p?=?0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥?3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients’ MYD88 mutation status.     

ACUTE LEUKEMIAS XVI

Few studies have examined the prognostic impact of blood markers [other than the five factors in the enhanced International Prognostic Index (NCCN-IPI)] in elderly patients with diffuse large B cell lymphoma (DLBCL). We retrospectively analyzed 391 DLBCL patients receiving rituximab plus anthracycline-containing chemotherapy to examine the prognostic impact of simple blood markers. The NCCN-IPI was more accurate for discriminating prognoses than the original IPI. Multivariate analysis identified platelet count (<100,000/μl) and albumin (<3.5 g/dl) levels as significantly associated with lower overall survival (OS), independently of the NCCN-IPI. These parameters stratified patients into three risk groups: platelet–albumin (PA) score low (platelet count ≥100,000/μl, albumin ≥3.5 g/dl, n?=?243); intermediate (platelet count <100,000/μl, albumin ≥3.5 g/dl or platelet count ≥100,000/μl, albumin <3.5 g/dl, n?=?125); and high (platelet count <100,000/μl, albumin <3.5 g/dl, n?=?23). The 5-year OS rates were 81.5, 48.6, and 20.2 %, respectively (p?<?0.001). Notably, most patients with a low platelet count (n?=?30) were stratified into the high-risk subgroup, suggesting that platelet count was prognostic for high-risk patients with a dismal outcome. In elderly patients (n?=?291), the prognostic value of the NCCN-IPI might be diminished because the low-risk category was excluded; however, the PA score was predictive of survival: the 5-year OS rates for PA score low (n?=?171), intermediate (n?=?101), and high (n?=?19) groups were 77.6, 47.9, and 19.0 %, respectively (p?<?0.001). Platelet count and albumin levels are useful prognostic factors, and their combined use can predict survival, even in elderly patients.     

Final analysis of the randomised PEAK trial: overall survival and tumour responses during first-line treatment with mFOLFOX6 plus either panitumumab or bevacizumab in patients with metastatic colorectal carcinoma

Purpose

To report planned final overall (OS) and progression-free survival (PFS) analyses from the phase II PEAK trial (NCT00819780).

Methods

Patients with previously untreated, KRAS exon 2 wild-type (WT) metastatic colorectal cancer (mCRC) were randomised to mFOLFOX6 plus panitumumab or bevacizumab. The primary endpoint was PFS; secondary endpoints included OS, objective response rate, duration of response (DoR), time to response, resection and safety. Treatment effect by tumour RAS status was a prespecified objective. Exploratory analyses included early tumour shrinkage (ETS) and depth of response (DpR).

Results

One hundred seventy patients had RAS WT and 156 had RAS WT/BRAF WT mCRC. Median PFS was longer for panitumumab versus bevacizumab in the RAS WT (12.8 vs 10.1 months; hazard ratio (HR) = 0.68 [95% confidence intervals (CI) = 0.48–0.96]; p = 0.029) and RAS WT/BRAF WT (13.1 vs 10.1 months; HR = 0.61 [95% CI = 0.42–0.88]; p = 0.0075) populations. Median OS (68% OS events) for panitumumab versus bevacizumab was 36.9 versus 28.9 months (HR = 0.76 [95% CI = 0.53–1.11]; p = 0.15) and 41.3 versus 28.9 months (HR = 0.70 [95% CI = 0.48–1.04]; p = 0.08), in the RAS WT and RAS WT/BRAF WT populations, respectively. Median DoR (11.4 vs 9.0 months; HR = 0.59 [95% CI = 0.39–0.88]; p = 0.011) and DpR (65.0 vs 46.3%; p = 0.0018) were improved in the panitumumab group. More panitumumab patients experienced ≥30% ETS at week 8 (64 vs 45%; p = 0.052); ETS was associated with improved PFS/OS. No new safety signals occurred.

Conclusions

First-line panitumumab + mFOLFOX6 increases PFS versus bevacizumab + mFOLFOX6 in patients with RAS WT mCRC.

     

Outcomes of previously untreated elderly patients with AML: a propensity score-matched comparison of clofarabine vs. FLAG

The 5-year overall survival (OS) in patients ≥?60 years old with acute myeloid leukemia (AML) remains <?10%. Clofarabine-based induction (CLO) provides an alternative to low-intensity therapy (LIT) and palliative care for this population, but supporting data are conflicted. Recently, our institution adopted the FLAG regimen (fludarabine, cytarabine, and granulocyte colony-stimulating factor) based on data reporting similar outcomes to CLO in elderly patients with AML unable to tolerate anthracycline-based induction. We retrospectively analyzed the efficacy and safety of patients ≥?60 years old with AML treated with FLAG or CLO over the past 10 years. We performed a propensity score match that provided 32 patients in each group. Patients treated with FLAG had a higher CR/CRi rate (65.6 vs. 37.5%, P?=?0.045) and OS (7.9 vs. 2.8 months, P?=?0.085) compared to CLO. Furthermore, FLAG was better tolerated with significantly less grade 3/4 toxicities and a shorter duration of neutropenia (18.5 vs. 30 days, P?=?0.002). Finally, we performed a cost analysis that estimated savings to be $30,000–45,000 per induction with FLAG. Our study supports the use of FLAG both financially and as an effective, well-tolerated high-dose treatment regimen for elderly patients with AML. No cases of cerebellar neurotoxicity occurred.     

Cytochrome P450 1B1 (CYP1B1) polymorphisms are associated with clinical outcome of docetaxel in non-small cell lung cancer (NSCLC) patients

Purpose

Cytochrome P450 1B1 (CYP1B1) is involved in the metabolism of anticancer agents; its overexpression was associated with resistance to docetaxel, a commonly used drug for second-line treatment of NSCLC. Several functional single nucleotide polymorphisms (SNPs) have been associated with CYP1B1 expression and activity. The objective of this study was to retrospectively evaluate the correlation of CYP1B1 SNPs with the outcome of NSCLC patients treated with docetaxel in second or third line.

Methods

Associations between CYP1B1 4326C>G and 4390A>G polymorphisms with response, progression-free survival (PFS) and overall survival (OS) were estimated using Pearson χ² test, Kaplan–Meier curves and log-rank test; a multivariate analysis was performed using Cox proportional hazards modeling.

Results

A total of 65 advanced NSCLC patients were enrolled into the analysis. Median age was 66 years (range 46–81). Forty-nine patients were male; only five were never smokers. Performance status (PS) was 0 in 25 patients, 1 in 28 and 2 in 12. Histology was adenocarcinoma in 28 patients, squamous carcinoma in 22, other NSCLC in the remaining 15. At univariate analysis, stage and CYP1B1 4326C>G SNPs are associated with PFS, while PS and CYP1B1 4326C>G SNPs correlated with OS. In particular, patients with CYP1B1 4326-GG genotype had shorter PFS and OS than patients with other genotypes (PFS 1.80 vs. 2.70 months, p = 0.12; OS 3.63 vs. 9.83 months, p = 0.039). CYP1B1 4326C>G SNPs were also associated with response rate. Multivariate analysis confirmed the independent prognostic/predictive role of CYP1B1 4326C>G SNPs on OS (p = 0.042) with only a trend for PFS (p = 0.083).

Conclusions

CYP1B1 4326C>G polymorphism emerged as possible prognostic/predictive marker of activity and efficacy of docetaxel in NSCLC patients.

     

Impact of age and comorbidities on the efficacy of FC and FCR regimens in chronic lymphocytic leukemia

CLL is an aging-associated neoplasm with median age at diagnosis >?65 years. Little is known about safety and efficacy of FC/FCR regimens in elderly CLL patients with multiple comorbidities. We retrospectively revised medical records of 90 patients treated with FC/FCR regimens in our clinic. Data on demographic and biological characteristics, comorbidities, response to therapy, and treatment-associated adverse events were analyzed. Compared to FC, FCR yielded higher rates of OR (93.6 vs. 81.4%, p?=?.109) and CR (72.3 vs. 46.5%, p?=?.018). This translated in longer EFS (median 52 vs. 19 months, p?=?<.001) and OS (median 89 vs. 45 months, p?=?.001). Elderly patients (≥?65 years) had more comorbidities and higher median CIRS-G score (7 vs. 4, p?<?.001). However, no association was found between CIRS-G score and survival. Decreased renal function was associated with dismal prognosis in patients treated with FCR.     

Temporal trajectory of quality of life and its predictors in recipients of hematopoietic stem cell transplantation

This prospective longitudinal study evaluated the temporal trajectory of health-related quality of life (HRQOL) and its associated factors in patients who received hematopoietic stem cell transplantation (SCT) 6 months after transplantation. Eighty-nine adult patients who were admitted to Seoul National University Hospital for SCT were consecutively included in the study. The participants completed three standardized questionnaires: Insomnia Severity Index, Hospital Anxiety and Depression Scale, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire. The participants completed the study questionnaires at three time points: before SCT (T1), immediately after SCT (T1), and 6 months after SCT (T3). Immediately after SCT, HRQOL decreased significantly (p?<?0.001), followed by recovery over 6 months. The conditioning regimen for SCT showed no correlation with HRQOL at T2 (p?=?0.283) or T3 (p?=?0.799), with no significant difference in HRQOL between allogeneic and autologous SCT recipients at T2 (p?=?0.829) or T3 (p?=?0.824). Depression (p?=?0.042), pain (p?=?0.023), and appetite loss (p?=?0.004) negatively influenced HRQOL at T1, whereas only pain (p?=?0.048) remained an important factor at T2. Six months after SCT, the two most frequent symptoms, fatigue and financial problems, became major factors (p?=?0.004 and p?=?0.005, respectively). Depression began to play an important role in HRQOL again at T3 (p?=?0.040). These findings demonstrate that SCT recipients need both psychological and medical support to achieve a better HRQOL after SCT.     

Association of bone marrow fibrosis with inferior survival outcomes in chronic myelomonocytic leukemia

The impact of bone marrow fibrosis grade on the prognosis of patients with chronic myelomonocytic leukemia (CMML) remains controversial. Therefore, we examined the records of 82 patients diagnosed with CMML at our institution and summarized baseline characteristics and molecular profiles by subgroups of absent or mild (grades 0/1) and moderate (grade 2) fibrosis. Cox proportional hazards models were constructed to assess the prognostic significance of fibrosis grade. Grade 2 fibrosis was identified in 63 patients (76.8%), grade 1 in 16 patients (19.5%), and grade 0 in 3 patients (3.7%). Grade 2 fibrosis was associated with reduced hemoglobin levels (median 9.75 vs 11.0 g/dL in grade 0/1; p?=?0.04) and increased percentages of ringed sideroblasts (7.5 vs 0%; p?=?0.008). In multivariable analysis, grade 2 fibrosis was an independent predictor of poor overall survival (OS; 95% CI 1.32–6.35; HR 2.90; p?=?0.008), but not event-free survival (EFS; 95% CI 0.62–2.67; HR 1.28; p?=?0.50). Absolute neutrophil count (ANC) was found to impact OS (95% CI 1.01–1.09; HR 1.05; p?=?0.009), while both ANC (95% CI 1.00–1.07; HR 1.04; p?=?0.04) and peripheral blood blast percentage (95% CI 1.02–1.32; HR 1.16; p?=?0.02) impacted EFS. These results implicate fibrosis grade is an important indicator of prognosis, with high-grade fibrosis predicting inferior survival. Given the prevalence of marrow fibrosis in CMML, fibrosis grading should be incorporated into prognostic assessment and therapeutic decision-making.     

Coronary Artery Bypass Grafting in Elderly Patients: Insights from a Comparative Analysis of Total Arterial and Conventional Revascularization

The benefits of total arterial (TAR) versus conventional (CR) revascularization are controversial in the higher-risk cohort of elderly patients. Taking for granted its benefit on long-term survival, we evaluated the effect of TAR on safety (death, myocardial infarction, and stroke) of patients undergoing CABG. Between 2000 and 2009, 487 patients >75 years underwent isolated CABG at our institution (150 TAR and 337 CR). Patients with arterial free-grafts were excluded. After propensity matching, the outcomes of 131 TAR and 127 CR patients were compared. TAR patients had lower incidence of post-operative myocardial infarction (p?=?0.025) and stroke (p?=?0.005). They also experienced shorter intensive care unit (p?=?0.046) and ward stay (p?=?0.028), lower output of TnI (p?=?0.035), and less wound complications (leg included) (p?=?0.0001), while mortality was comparable (p?=?0.57). In our cohort of elderly patients with multivessel disease, TAR was associated with lower rates of myocardial infarction, stroke, and shorter hospital stay.     

Donor-recipient killer immunoglobulin like receptor (KIR) genotype matching has a protective effect on chronic graft versus host disease and relapse incidence following HLA-identical sibling hematopoietic stem cell transplantation

Impact of donor-recipient killer immunoglobulin-like receptor (KIR) gene-gene matching on transplant outcomes is still inconclusive. Recent data suggest that killer cell immunoglobulin-like receptor (KIR) regulated natural killer cell (NK cell) activity may contribute to graft versus leukemia (GvL) effects and graft versus host disease (GvHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). This case-control study aims to evaluate the effects of both aKIR and iKIR donor-recipient genotype matching on the outcomes of T cell replete HLA-identical sibling allo-HSCTs in a homogenous young patient population with myeloid leukemias. Five transplant outcomes including relapse rate (RR), disease-free survival (DFS), overall survival (OS), cumulative incidences of acute GvHD (aGvHD), and chronic GvHD (cGvHD) are investigated. Out of 96 HLA-identical sibling donor-recipient pairs, 34 were matched for activating KIR (aKIR), 38 for inhibitory KIR (iKIR), and 20 for both aKIR and iKIR. Fourty-four pairs were mismatched for both iKIR and aKIR. In univariate analysis, aKIR-matching resulted with a decrease in relapse rate (RR) (hazard ratio [HR]: 0.4; p?=?0.04) and an increase in disease-free survival (DFS) (HR: 0.5; p?=?0.03). In addition, cGvHD ocurred less frequently in the aKIR-matched (odds ratio [OR]: 0.4; p?=?0.04) or iKIR-matched (OR: 0.3; p?=?0.009) cohorts. Matching for both aKIR and iKIR was also associated with a decrease in cGvHD incidence (OR: 0.3; p?=?0.02). iKIR-matching had no effects on RR, OS, or DFS. Analysis of donor haplotype effects showed haplotype-BB to have a tendency towards reduced relapse rate (HR: 0.4; p?=?0.08) and better OS (HR: 0.4; p?=?0.04); haplotype-Bx to increase the incidence of cGvHD (OR: 4.1; p?=?0.03). In multivariate analysis, DFS advantage remained significant for aKIR-matching (HR: 0.5; p?=?0.04); cGvHD incidence was reduced in the presence of iKIR-match (OR: 0.3; p?=?0.02) and increased in the presence of haplotype-AB and -BB donors (OR: 7.9; p?=?0.02; OR: 5.1; p?=?0.03, respectively). In an attempt to investigate the pathogenesis underlying KIR-matching, we searched for residual NK/T cells on day 0 peripheral blood samples of six additional recipients and noted the presence of CD3⁺ (7.0–91.4?×?10⁶/L) and CD56⁺57⁺ (0.8–12.7?×?10⁶/L) cells. In conclusion, conditioning regimen surviving recipient NK/T cells potentially influenced by KIR-matching may contribute to GvL/GvH reactions.     

Nucleic acid based risk assessment and staging for clinical practice in multiple myeloma

The recently introduced Revised International Staging System (R-ISS) for multiple myeloma (MM) integrates albumin, β2 microglobulin, lactate dehydrogenase (LDH) with high-risk cytogenetic aberrations (CA), i.e., t(4;14) and t(14;16) and del17p using fluorescent in situ hybridization (FISH). We evaluated utility of nucleic acid-based tests of multiplex ligation-based probe amplification (MLPA) and quantitative real-time polymerase chain reaction (qRT-PCR) to define the CA and the R-ISS categories as per this approach were evaluated for their ability to predict outcome in terms of response, progression-free (PFS), and overall survival (OS). In this study (n?=?180), 17 (9.4%), 118 (65.6%), and 45 (25%) patients were assigned to R-ISS1, R-ISS2, and R-ISS3 categories with statistically significant differences in median PFS (p?=?0.02) and OS (p?<?0.001).On univariate analysis, serum creatinine, LDH, 17p deletion, chromosome 1q gain, and response after first induction therapy were associated with statistically significant differences (p?<?0.05) in PFS and in addition, age>?65 years and use of triplet therapy with OS. On multivariate analysis, only serum creatinine, LDH, and response after first induction therapy retained significance for predicting PFS and in addition, use of triplet therapy retained significance for the OS. The proposed nucleic acid-based algorithm using qRT-PCR and MLPA for R-ISS is resource-effective in terms of small quantities of sample required; feasibility of batch processing and reduced overall cost for the total number of regions evaluated and retained the prognostic significance of R-ISS, making it suitable for clinical practice for molecular characterization of MM.     

Oncologic outcome of colorectal cancer patients over age 80: a propensity score-matched analysis

Purpose

It remains unclear whether old age is a poor prognostic factor in colorectal cancer (CRC). We compared oncologic outcomes in CRC patients according to age, using 80 as the dividing point.

Methods

CRC patients who underwent radical surgery from 2000 to 2011 were evaluated. We performed matched and adjusted analyses comparing oncologic outcomes between patients with ≥?80 and <?80 years old.

Results

Among 9562 patients, 222 were elderly. The median age was 82.0 years in elderly patients and 59.0 years in young patients. Elderly patients received less neoadjuvant or adjuvant therapy compared to young patients (p?<?0.001). After recurrence, significantly fewer elderly patients received additional treatments (p?<?0.001). Before matching, disease-free survival (DFS) and cancer-specific survival (CSS) were significantly lower for elderly patients compared to those for young patients (p?<?0.001 and p?<?0.001, respectively). After matching, DFS and CCS were not significantly different between the two groups (p?=?0.400 and p?=?0.267, respectively). In a multivariate analysis for prognostic factors, old age was not an independent poor prognostic factor of DFS and CCS (p?=?0.619 and p?=?0.137, respectively).

Conclusions

Elderly patients aged ≥?80 years with CRC had similar oncologic outcome to young patients, and age was not an independent prognostic factor.

     

Impact of hematopoietic stem cell transplantation in patients with relapsed or refractory mantle cell lymphoma

Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) still have a poor prognosis, and the choice between high-dose therapy with autologous hematopoietic cell transplantation (HCT) and allogeneic HCT remains controversial in these patients. We retrospectively analyzed the risk factors for outcomes in 162 R/R MCL patients who received autologous (n?=?111) or allogeneic (n?=?51) HCT between 2004 and 2014. The median overall survival (OS) rates were 48 and 65 months in the autologous and allogeneic HCT groups, respectively (P?=?0.20). Significant risk factors for overall survival in R/R MCL patients after autologous HCT were >?60 years of age at HCT (P?=?0.017), higher score of HCT-specific comorbidity index at HCT (P?=?0.033), and receiving MCEC (ranimustine?+?carboplatin?+?etoposide?+?cyclophosphamide) regimen (P?=?0.017), while higher performance status at HCT (P?=?0.011) and longer interval from diagnosis to HCT (P?=?0.0054) were risk factors after allogeneic HCT. Strategies that carefully select R/R MCL patients for autologous HCT may allow the identification of individuals suitable for allogeneic HCT.