Cycles Of Combination Chemotherapy Research Articles

Updates in Cardiac Amyloidosis: A Review

Systemic amyloidosis is a relatively rare multisystem disease caused by the deposition of misfolded protein in various tissues and organs. It may present to almost any specialty, and diagnosis is frequently delayed.[1][1] Cardiac involvement is a leading cause of morbidity and mortality, especially

Ventricular fractional shortening in 108 dogs with malignant lymphoma undergoing chemotherapy with a cyclic combination protocol including doxorubicin

The aim of this study was to evaluate whether changes in the left ventricular fractional shortening (LVFS) can be detected in dogs with malignant lymphoma undergoing a cyclic combination chemotherapy protocol including doxorubicin. Left ventricular fractional shortening as a stand-alone measurement will not show a significant change during the cyclic combination protocol. In this retrospective study, the records of dogs with malignant lymphoma treated between April 2001 and October 2010 were reviewed. Inclusion criteria comprised: a diagnosis of malignant lymphoma, a cyclic combination chemotherapy (including L-asparaginase, vincristine, cyclophosphamide, doxorubicin and prednisolone), and an echocardiographic examination by an experienced examiner before treatment and after each doxorubicin administration. One hundred and eight dogs were included and a total of 446 LVFS measurements had been performed. Patients were divided into four groups according to the number of doxorubicin administrations. Median LVFS did not change significantly during the cyclic combination protocol in all groups. All median LVFS values remained above the lower reference value of 25%. The measurement of LVFS did not show a significant change during the cyclic combination protocol treatment including doxorubicin in this population of dogs. Therefore either this cyclic combination protocol does not cause a systolic dysfunction or LVFS is not sensitive enough to detect early changes. Newer methods that are more sensitive then LVFS might be necessary to detect such changes.

A Case of Pulmonary Artery Intimal Sarcoma Masquerading as Pulmonary Embolism

Pulmonary artery intimal sarcoma is a rare tumor with no characteristic symptoms. It is frequently misdiagnosed as pulmonary embolism. We report a case of pulmonary artery intimal sarcoma in a 48-year-old man with dyspnea, cough and blood-tinged sputum. He was initially suspected and treated as a pulmonary embolism. Computed tomography of the chest showed filling defects occupying the entire luminal diameter of the right and left pulmonary artery as well as extraluminal extension of the intraluminal mass. Surgical resection of the tumor confirmed pulmonary artery intimal sarcoma. After surgery, he received 8 cycles of combined chemotherapy consisting of doxorubicin and ifosfamide. After 8 cycles, Computed tomography of the chest showed interval regression of the residual tumor. Radiotherapy was done as tota l 6,000 cGy for 5 weeks, following the 8th chemotherapy. The patient's condition was successfully stabilized with chemotherapy and radiotherapy.

Primary penile lymphoma: 18f-fdg pet-CT for accurate staging and response monitoring

Primary penile lymphoma is an extremely rare neoplasm. We present a case of 63-year-old man with painless diffuse pe- nile swelling and retention of urine. Biopsy from the penile swelling demonstrated CD20+ diffuse large B-cell lymphoma. Staging was performed using fluorine-18-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) and revealed a FDG avid penile mass with enlarged and FDG avid multiple inguinal and aortocaval lymph nodes. A follow-up FDG PET-CT scan after eight cycles of combination chemotherapy showed complete remission of the dis- ease. Thus, FDG PET-CT should be integrated in management protocols of rare primary penile lymphoma.

Etoposide, vincristine, doxorubicin and dexamethasone (EVAD) combination chemotherapy as second-line treatment for advanced AIDS-related Kaposi’s sarcoma

To evaluate through retrospective analysis the efficacy and toxicity of combination chemotherapy with etoposide, vincristine, doxorubin and dexamethasone (EVAD) as second-line therapy in patients with advanced AIDS-related Kaposi's sarcoma (AIDS-KS) after failure of first-line chemotherapy. Eighty-eight patients with poor-risk AIDS-KS were treated intravenously with combination chemotherapy with EVAD; etoposide at a dose of 100 mg/m(2) on three consecutive days, vincristine 1.4 mg/m(2) with a maximum single dosage of 2.0 mg on day one, doxorubicin 30 mg/m(2) on day one and dexamethasone 40 mg on three consecutive days, with a three week cycle. All eligible patients had relapsed or progressed after prior two to six cycles of combination chemotherapy with doxorubicin, bleomycin and vincristine (ABV) or bleomycin and vincristine (BV). Assessment of the response of all the patients was made. The overall objective response rate was 59.1% (95% CI 48.83-69.37%), with five complete responses and 47 partial responses. Twenty-six cases of stable disease and 10 of progressive disease were observed in the remaining patients. The median follow-up period was 27 months (range 8-52 months). The median time to progression was 6.80 months (95% CI 2.04-11.56 months), and the median overall survival was 14.24 months (95% CI 10.26-18.22 months). Leucopenia was seen in 92.0% of patients, of which 20 patients had grade 3 and 12 had grade 4. Conclusions Combination chemotherapy with EVAD offers a new, active and safe therapeutic approach for the treatment of advanced AIDS-related KS.

Total Therapy 6: Initial Results of Dose-Dense Strategy for Previously Treated Multiple Myeloma

Abstract 3081 Background:We have reported extensively on applying dose-intense total therapy approach in newly diagnosed multiple myeloma (MM), yielding long CR durations in ∼80% GEP-defined low-risk myeloma patients. Herein, we present for the first time the initial results of a phase II trial employing a dose-dense approach in previously treated MM. Patients & Methods: Patients received 5 cycles of combination chemotherapy (Figure 1) followed by maintenance with bortezomib, lenalidomide and dexamethasone until relapse or disease progression by IMWG 2006 criteria. Overall survival and progression free survival were estimated using the Kaplan-Meier method. Survival distributions were compared using the log-rank test. Results: 63 patients with previously treated MM were enrolled. The median follow-up from enrollment was 15.6 months. Baseline characteristics included age >=65yr in 37%, ISS stage II/III was seen in 41%/19% of patients, cytogenetic abnormalities (CA) in 37%, and GEP-70 high risk-MM (HRMM) in 26% of patients with available gene expression data. 11 patients (17%) had >2 prior lines of therapy including regimens that contained bortezomib (91%), thalidomide(45%), lenalidomide(81%), melphalan(27%) and steroids(100%). 14 patients (22%) discontinued therapy primarily due to progression, death or toxicity. Cumulative incidence of PR/VGPR/CR at 18 months was 69.4%, 54.8% and 37.0% respectively. Of the 60 patients with at least 3 months of follow-up, 33% had stable disease as the best overall response. The time to achieving PR or better at 6 months was more rapid in HR-MM vs LRMM (63.6% vs. 50%, p=0.008). Hematologic toxicities occurred in all patients (100%), whereas the most common non-hematologic toxicities counting all toxicities (>grades 3) included metabolic/electrolyte disturbances (95%) followed by infections (31%), hepatobiliary (20%) and gastrointestinal (16%) toxicities. Overall survival (OS) and progression free survival (PFS) at 12 months was 90% and 87%, respectively (Figure 2). The OS (96% vs 60%, p=0.0002) and PFS (92% vs 53%, p<0.0001) at 12 months was markedly superior in GEP-70 defined low-risk MM (LRMM) compared with high-risk MM (HRMM). ISS staging and GEP-defined p53 deletion did not impact OS/PFS at 12 months. Conclusions: Dose-dense strategy is highly effective in previously treated LRMM. Even though time to achieving best response was quicker in HRMM, response duration was shorter thus augmenting the significance of sustaining best response rather than depth of response in HR-MM. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

An economic analysis of dose dense weekly paclitaxel plus carboplatin versus every-3-week paclitaxel plus carboplatin in the treatment of advanced ovarian cancer

ObjectiveCompared with every-3-week paclitaxel (q3T) plus carboplatin, dose-dense weekly paclitaxel (ddT) plus carboplatin improved the survival of ovarian cancer patients. We performed a cost analysis comparing these two regimens. MethodsUsing a Markov decision model, an acceptable incremental cost-effectiveness ratio (ICER) per progression-free life-year saved (PFLYS) was estimated. Cost of drugs, growth colony-stimulating factors, and transfusions were derived from Medicare reimbursement data. Survival and rates of complications were estimated based on the clinical trial. ResultsUsing a body weight and surface area of an average woman age 63, the estimated cost per cycle of ddT was $107 vs. $80 for q3T. The costs per cycle of combination chemotherapy including treatment administration were $873 for ddT and $535 for q3T. With a median progression-free survival (PFS) of 28months with ddT vs. 17.2months with q3T, the ICER was $5809 per PFLYS for ddT compared with q3T arm. Using a maximum ICER of $100,000 per LYS as cost-effective threshold, the ddT regimen was cost-effective. The ICER was most sensitive to the hazard rate for difference in PFS between the two regimens. A 4-month difference in PFS resulted in a $1200 change of ICER per PFLYS. The ICER was also sensitive to overall survival difference, rate of hematological toxicity, and rate of discontinuation. ConclusionsIn this economic model, dose-dense weekly paclitaxel is a cost-effective treatment option for advanced ovarian cancer.

PREPARE trial: a randomized phase III trial comparing preoperative, dose-dense, dose-intensified chemotherapy with epirubicin, paclitaxel, and CMF versus a standard-dosed epirubicin–cyclophosphamide followed by paclitaxel with or without darbepoetin alfa in primary breast cancer—outcome on prognosis

BackgroundThe objective of this study was to compare the effect of dose-intensified neoadjuvant chemotherapy with that of standard epirubicin plus cyclophosphamide followed by paclitaxel in combination with or without darbepoetin on survival in primary breast cancer. Patients and methodsA total of 733 patients received either four cycles of neoadjuvant epirubicin 90 mg/m2 plus cyclophosphamide 600 mg/m2 every 3 weeks followed by four cycles of paclitaxel 175 mg/m2 every 3 weeks (EC→T), or three cycles of epirubicin 150 mg/m2 every 2 weeks followed by three cycles of paclitaxel 225 mg/m2 every 2 weeks followed by three cycles of combination chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (Edd→Tdd→CMF). The patients were randomly assigned to receive darbepoetin or none. The primary objective was to demonstrate a superior disease-free survival (DFS) of Edd→Tdd→CMF compared with EC→T. ResultsEstimated 3-year DFS was 75.8% with EC→T versus 78.8% with Edd→Tdd→CMF [hazard ratio (HR) 1.14; P = 0.37] and overall survival (OS) 88.4% versus 91.5% (HR 1.26; P = 0.237). Three-year DFS was 74.3% with darbepoetin versus 80.0% without (HR 1.31; P = 0.061) and OS 88.0% versus 91.8% (HR 1.33; P = 0.139). Patients with a pathologically documented complete response [pathological complete response (pCR)] had a significantly better DFS compared with those without achieving a pCR (estimated 3-year DFS: 89.2% versus 74.9%; HR 2.27; P = 0.001). ConclusionNeoadjuvant dose-intensified chemotherapy compared with standard chemotherapy did not improve DFS, whereas the addition of darbepoetin might have detrimental effects on DFS.

Continued pemetrexed and platin-based chemotherapy in patients with malignant pleural mesothelioma (MPM): Value of 18F-FDG-PET/CT

To prospectively analyze different FDG-PET/CT-parameters (modified RECIST, SUVmax, TLG, PETvol) in patients with malignant pleural mesothelioma (MPM) under continued pemetrexed and platin based treatment. Patients with biopsy proven MPM undergoing treatment with pemetrexed and platin based treatment were prospectively included in the study. Integrated FDG-PET/CT imaging was performed within 2 weeks before therapy and after every three consecutive cycles of combined chemotherapy. All CT-images were evaluated according to the modified RECIST (modRECIST) criteria. All FDG-PET/CT images were analyzed using SUVmax (maximum Standard Uptake Value) according to the EORTC criteria, change in Total Lesion Glycolysis (TLG) and FDG volume (PETvol). Percent change in all parameters compared to the initial, pre-therapeutic and the previous FDG-PET/CT scan. ModRECIST, EORTC guidelines, increase or decrease in TLG and PETvol was correlated with overall survival (OS) using the Log Rank Test. 41 patients with MPM were prospectively included in this study. The median OS of the study population is 439 days (111-1128). 41 patients had initial staging, 41 patients completed 3 cycles, 28 patients completed 6 cycles, 19 patients completed 9 cycles, 11 patients completed 12 cycles, 5 patients completed 15 cycles, 4 patients completed 18 cycles and 1 patient completed 21 cycles of chemotherapy. Chemotherapy was well tolerated up to 21 cycles. SUVmax showed a high variance over time for individual patients and change in SUVmax using EORTC guidelines did not predict OS at any time point. Ongoing morphological response in CT using modRECIST had highest correlation with OS and predicted survival up to the 15th cycle of continued permetrexed and platin based treatment. The correlations of response of the volume based PET parameters (TLG and PETvol) and OS are inferior to the morphological modRECIST parameter. Permetrexed and platin based treatment in MPM patients can be given over a prolonged time with good tolerance. Therapy response should be assessed by modRECIST in CT but not with SUVmax in FDG-PET. Long term permetrexed and platin therapy should be considered in MPM patients with good tolerance of treatment and ongoing morphological response in CT.

Predictive value of d-dimer in response to chemotherapy in advanced-stage lung cancer patients

Objective To evaluate the association and predictive value of D-dimer levels with chemotherapy response in advanced-stage lung cancer patients. Methods 59 patients and 30 healthy persons were evaluated and analysed; 39 patients had non-small-cell lung cancer (NSCLC) and 20 small-cell lung cancer (SCLC) and all were at an advanced stage. D-dimer levels were measured before and after 3 cycles of combination chemotherapy. D-dimer was measured with Latest method in SAGO STA-Compact Automatic analyzer. Results The level of D-dimer in 59 advanced-stage lung cancer patients was significantly higher than that of normal control (P＜0.01). Not only NSCLC cases but also SCLC patients,D-dimer levels were significantly different between Ⅲ and Ⅳ stage lung cancer. After chemotherapy, the level of D-dimer in NSCLC patients with PR/CR was markedly reduced (P＜0.01), but increased (P＜0.01) in PD cases, and not changed in SD patients. But, we found there were no significant difference in Ddimer plasma levels of SCLC cases for both PR/CR cases and PD patients. Conclusion D-dimer plasma levels decrease or increase after response and progressive disease, respectively. It can act as a predictive factor of the evolution of progressive disease with lung cancer, especially for NSCLC. Key words: Lung cancer; D-dimer; Chemotherapy; Prognosis

A European Collaborative Study of Treatment Outcomes In 428 Patients with Systemic AL Amyloidosis

AbstractAbstract 988The treatment of patients with systemic AL amyloidosis remains challenging. Cyclical combination chemotherapy is used in majority of patients but a report that I.V. melphalan-dexamethasone may not overcome the poor prognosis for cardiac amyloidosis (Deitrich S et al, Blood, 116, 2010) has fuelled the controversy about best front line treatment. We report outcomes of 428 patients treated with oral cyclophosphamide thalidomide dexamethasone (CTD), oral melphalan dexamethasone (M-dex), bortezomib dexamethasone with or without an alkylator (BD), cyclophosphamide-lenalidomide-dexamethasone (CLD) or stem cell transplant (ASCT) as first line treatment for systemic AL amyloidosis assessed at three large European amyloid centres in London (UK), Pavia (Italy) and Athens (Greece) between 2003–2010. Patients with a full baseline data set were included in the study. Clonal and organ responses were defined according to the international amyloidosis consensus statement (Gertz et al 2005) and responses were assessed at 6 months or at the end of treatment. dFLC (difference between involved and uninvolved free light chain (FLC)) was used to assess the absolute FLC change after treatment.204 (48%) received M-dex, 155 (36%) received CTD, 13 (3%) received ASCT, 28 (7%) received BD and 25 (6%) received CLD. The median number of cycles received was 5 for all regimens. 257 (60%) had cardiac involvement, 325 (76%) had renal and 59 (14%) had liver involvement. Cardiac involvement by regime was: BD 75%, CLD 68%, M-dex 65%, CTD 45% and ASCT 23%. 30 (7%) died within six months of diagnosis. The median number of organ involved was 2 (range 1–5) with ECOG performance status ≥2 in 123 (28%). 98 (23%) patients achieved a complete response (CR), 175 (41%) achieved a partial response (PR) and 125 (29%) did not respond to treatment. A haematological CR/PR was seen, respectively, in 22%/41% treated with CTD, 26%/44% with M-dex, 23%/46% with ASCT, 39%/42% with BD and 4%/44% with CLD. There was significantly greater reduction in dFLC after BD (median reduction 91% over starting value) compared to CTD (median 81%; p = 0.006), M-Dex (median 83%; p = 0.004) and CLD (median 72%; p = 0.03). There was no significant difference in the median dFLC reduction between patients treated with CTD and M-Dex. 100/325 (30%) had a renal organ response, 17/59 (29%) had a hepatic response and 24/257 (9%) had a cardiac response, and 61 (16%) had a cardiac response by NT-proBNP criteria. The organ and NT-proBNP responses respectively were highest in the cohort treated with BD (53% and 32%) followed by CTD (38% and 12%), ASCT (30%), M-dex (23% and 19%) and CLD (12% and nil). CTD achieved significantly better organ responses compared to M-dex (p=0.0024). At median follow up of 29 months, median overall survival (OS) for the whole cohort has not been reached with 2, 3 and 4 year estimated survival of 75%, 65% and 61%, respectively. When patients with cardiac involvement were considered, those achieving a CR have not reached median OS with an estimated 3 year survival of 89%, those with PR had an estimated median OS of 50 months and the non-responders had a median OS of 21 months. Detailed comparison by Mayo stage will be presented. There was no significant difference in the OS of patients treated with CTD or M-Dex (as compared directly or by centre).In summary, outcome of patients with AL amyloidosis across three major European centres appears comparable. BD treatment achieves significantly lower end of treatment dFLC values compared to CTD, M-dex, ASCT or CLD – which importantly translates into an organ response in over half of all patients receiving BD compared to a third of those treated with CTD and quarter of those with M-dex and further follow up may yet reveal survival differences. Organ responses appear significantly better with CTD compared to M-dex – possibly due to more rapid response to CTD since the end of treatment dFLC values are not significantly different - although this does not translate into a survival advantage. Depth of clonal response appears to be directly linked to improvement in survival of patients with cardiac amyloidosis (including in patients treated with CTD and M-dex) and organ response in general. This study supports the rational for doing urgent phase III studies confirming benefits of bortezomib combination chemotherapy for upfront treatment in AL amyloidosis and the benefit of rapid deep clonal responses in cardiac amyloidosis irrespective of the regimen. Disclosures:Off Label Use: Thalidomide, bortezomib, lenalidomide. Dimopoulos:Celgene: Honoraria; Othro Boitech: Honoraria.

Repeat Laparoscopic Para-Aortic Lymphadenectomy of an Isolated Lymph Node Recurrence in Patient with Stage IB2 Cervical Cancer

Study Objective: To report a case of repeat laparoscopic para-aortic lymphadenectomy after surgery and concurrent chemoradiation of cervical cancer, FIGO stage IB2. Design: A case report. Setting: University teaching hospital. Patients: One patuient with isolated recurrent para-aortic lymph node. Intervention: Repeat Laparoscopic Para-aortic Lymphadenectomy. Measurements and Main Results: A 49-year-old woman had an isolated para-aortic lymph node recurrence 12 months after the initial treatment, F-18 fluoro-deoxyglucose-positron emission tomography-computed tomography showed left para-aortic lymph nodes with increased uptake of F-18 fluoro-deoxyglucose. This was successfully removed in a repeat LPAL. She received three cycles of combination chemotherapy and showed a complete clinical response. Conclusion: Repeat LPAL is thus a feasible and effective procedure to remove and confirm of an isolated para-aortic lymph node recurrence after previous surgery and chemoradiation for treating cervical cancer.

Ruptured ovarian endodermal sinus tumor diagnosed during pregnancy: Case report and review of the literature

Pregnancy complicated by endodermal sinus tumor of the ovary is a very rare event. We present a case report of a pregnant woman with a ruptured primary endodermal sinus tumor of the ovary that was diagnosed at 13 weeks of gestation. After right salpingo-oophorectomy had been performed the patient received four cycles of combination chemotherapy (bleomycin, etoposide, and cisplatin) starting at the 15th week of pregnancy. The patient did not have any evidence of tumor recurrence for 23 months. Her baby did not have any evidence of malformations and showed normal growth and development at 21 months of follow up.

Primitive neuroectodermal tumor of uterus — A rare entity

Primitive neuroectodermal tumor (PNET) of uterus is the rare of the rarest among the tumors of female genital tract. We herein reported a 32 years old female operated for lower abdominal lump, which was diagnosed, as PNET later confirmed by immunohistochemistry (IHC). She was lost to follow-up and presented 10 months later with recurrence. She was treated with cyclical combination chemotherapy followed by definitive surgery and is in complete remission at present.

Phase II trial of chemotherapy with temozolomide in combination with topotecan for central nervous system (CNS) metastases of solid tumors.

TPS145 Background: Patients with brain metastases of solid tumors have a poor prognosis, despite improvements in survival achieved with modern neurosurgical and radiation techniques. Chemotherapy does not play any significant role in this disease, but may have application in salvage of patients who have failed radiation therapy. In patients who are not surgical candidates, do not require immediate XRT to relieve symptoms and have controlled systemic disease, effective chemotherapy as an alternative to XRT might decrease the risk of radiation induced neurotoxicity. Both temozolomide and topotecan have good blood-brain barrier penetration and have shown activity in CNS malignancies. Preclinical studies suggest synergy of this drug combination. This is a single-arm, open-label phase II drug study. All patients will receive the chemotherapy combination. Up to 35 patients will be accrued over 2-3 years and followed for up to 5 years. Patients will receive up to 8 cycles of chemotherapy. The primary endpoint is the rate of radiologic response of brain metastases and secondary endpoints are median overall survival, progression-free survival, time to progression of brain metastases and toxicity. Methods: Each cycle is defined as a 28-day period. Patients will take oral temozolomide at bedtime nightly for 5 days on days 1 through 5 of each cycle. A chemotherapy-trained nurse will administer topotecan intravenously daily for 5 days on days 2 through 6 of each cycle. Contrast-enhanced MRI or CT scan of the brain and the sites of extracranial disease will be performed at baseline and every 2 cycles, until completion of the therapy or progression to evaluate response. Patients achieving complete remission (CR) will receive 2 more cycles of combined chemotherapy after CR is documented, but no less than 6 and no more than 8 cycles total. To be eligible: 1) Have failed prior WBRT or 2) not be candidates for surgical intervention and not require immediate radiation therapy to relieve symptoms, and have controlled systemic disease. No significant financial relationships to disclose.

Diffuse large B-cell non-Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Diffuse large B-cell non-Hodgkin's lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Primary Small Cell Carcinoma of the Upper Urinary Tract

We report a case of primary extrapulmonary small cell carcinoma of the distal ureter, with a synchronous small cell carcinoma of the ipsilateral renal pelvis. These tumors, rarely reported in the urinary tract, are locally aggressive and have a poor prognosis. A 77-year-old male bedridden patient presented with fever and chills with left side-flank pain for 3 days. Following a diagnosis of ureteral urothelial carcinoma, hand-assisted laparoscopic nephroureterectomy with bladder cuff excision was carried out. Adjuvant chemotherapy was given after pathologic report of primary small cell carcinoma of the distal ureter and a synchronous small cell carcinoma of the ipsilateral renal pelvis. After 3 cycles of combination chemotherapy, the patient died 4 months postoperatively due to sepsis.

Proliferation of CD4+CD25high+Foxp3+ regulatory T lymphocytes in ex vivo expanded ascitic fluid from primary and recurrent ovarian carcinoma

To the editor: It is well established that immunosurveillance has an important role in cancer development.1 Cancer immunosurveillance is considered an active and dynamic process of interaction between tumor cell and the host immune cells, such as natural killer cells (NK cells), dendritic cells, B-cells and T-cells. OF those immune cells, T-cells which are divided into two major subsets of CD4+ helper T cells (Th cells) and CD8+ cytotoxic T cells (CTL) are involved in establishing adaptive immune responses, which contribute to destroying cancer cells. On the other hand, regulatory T cells (Treg) are a specific subpopulation of lymphocytes that have immunosuppressive properties. In ovarian cancer, Curiel et al.2 demonstrated that Treg cells infiltration into cancer tissues suppress tumor specific T cell immune response. Barnett et al.3 also showed that there was an association between increased Treg cell infiltration and disease progress in ovarian cancers. We read with interest the article by Lee et al.4 The study by Lee et al. examined the differences of T cell subpopulations between before and after ex vivo expansion in ovarian cancer using flow cytometry. The authors isolated lymphocytes from ascitic fluids which were acquired from 19 primary ovarian cancer patients and 7 recurrent ovarian cancer patients and expanded those immune cells through ex vivo culture. The proportion of Th cells and Treg cells increased with expansion, while CTL decreased. Lymphocyte cells after ex vivo culture were larger in number in recurrent ovarian cancer than those in primary ovarian cancer. The authors showed that there were no significant differences in proportional changes of immune cells including CTL, Th cells and NK cells with ex vivo incubation between primary and recurrent ovarian cancers. However, Treg cells after ex vivo expansion in recurrent ovarian cancer were significantly higher than those in primary ovarian cancer. Through these results, the authors suggested that lymphocyte proliferation is more strongly suppressed at initial tumor stage and ex vivo expansion of T cells obtained from patients with ovarian cancer may increase the proportion of Treg cells. However, there are several issues to be discussed. First, the higher ex vivo expansion of Treg cells population in recurrent ovarian cancer might be due to the effect of chemotherapy. Several authors demonstrated that chemotherapy induced depletion of Treg cells in treating cancer and there was a relationship between Treg cell suppression and patients' prognosis.5,6 Second issue is the diagnostic criteria for recurrent ovarian cancer. The patients who were diagnosed with recurrent ovarian cancer had received only 1 cycle of chemotherapy. However, all their initial tumor stages were IIIc-IV. The standard treatment of advanced ovarian cancer is cytoreductive surgery followed by 6-8 cycles of combination chemotherapy with paclitaxel and carboplatin. Why did the patients diagnosed with recurrent ovarian cancer receive only 1 to 3 cycles of chemotherapy in their initial treatment? If the authors selected specific cases in recurrent ovarian cancer, selection bias might affect the result of their study.

A Case of Blastic Plasmacytoid Dendritic Cell Neoplasm Initially Mimicking Cutaneous Lupus Erythematosus

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare disease. The prognosis is poor in most cases with rapid progression despite administering chemotherapy. A 67-year-old man complained of skin rashes on his back and this spread to the trunk, face, arms and thighs, and he was initially diagnosed with cutaneous lupus erythematosus according to the skin biopsy. The skin rashes then became aggravated on a trial of low dose methylprednisolone for 3 months. Repeated skin biopsy revealed a diffuse infiltration of lymphoid cells with medium sized nuclei, positive for CD4 and CD56, negative for Epstein-Barr virus (EBV), indicating a diagnosis of BPDCN. Further workups confirmed stage IVA BPDCN involving the skin, multiple lymph nodes, the peripheral blood and the bone marrow. He was treated with six cycles of combination chemotherapy consisting of ifosphamide, methotrexate, etoposide, prednisolone and L-asparaginase, and he achieved a partial response. Herein we report on a rare case of BPDCN that was initially misinterpreted as cutaneous lupus erythematosus.

Phase III Randomized Stem Cell Mobilization Trial Comparing Standard Vs Double-Dose G-CSF Vs Standard Doses of G-CSF Plus GM-CSF in Hard to Mobilize Patients Undergoing An Autologous Hematopoietic Stem Cell Transplant (HSCT).

Abstract 3228Poster Board III-165 IntroductionUsing standard dose G-CSF (10 μg/kg) for stem cell mobilization, 25-40% of patients, deemed to be hard to mobilize based on prior therapy, will not collect sufficient HSC (> 2-2.5 × 106 CD34/kg) to proceed to a prompt autotransplant. Strategies to improve CD34/kg yields have included dose escalating G-CSF up to 30 μg/kg or combining G-CSF and GM-CSF. While dose escalated G-CSF is effective in increasing CD34 yields in normal donors as is the combination of G-CSF and GM-CSF, their comparative value in pre-treated patients has not been tested. To determine the value of these strategies, we performed a randomized comparison of high dose G-CSF (30 μg/kg as 2 doses 12 hours apart), to the combination of simultaneous single daily doses of G-CSF (10 μg/kg) plus GM-CSF (5 μg/kg), to a control group receiving G-CSF at an equivalent total dose of cytokine to the combination arm (15μg/kg) as a single dose. Patients and MethodsPatients were eligible if heavily pre-treated, defined as: a minimum of 10 total cycles of combination chemotherapy and two prior regimens, or a total of 6 chemotherapy cycles if the patient also received RT to marrow bearing sites, platinum-based chemotherapy or 2 or more cycles of any BCNU or fludarabine containing regimen. Baseline WBC had to be > 3000/μl, ANC > 1500/μl and a platelets > 100,000/μl. Twelve liter aphereses began on day 5 of mobilization, and continued until ≥ 4 × 106 CD34/kg were collected or a maximum of 5 aphereses. Patients typically proceeded to transplant if they had ≥ 2.5 × 106 CD34/kg collected and were always re-mobilized if they collected < 2.0 × 106 CD34/kg. CD34 subsets (CD34+/CD33- and CD34+/CD38-) were also assessed for the 3 groups to determine if more primitive HSC were mobilized by the 2 novel strategies. The sample size was calculated based as follows: 60% of the control group would collect 2.5 × 106 CD34/kg and this would rise to 90% in one or both study arms. The detection of such differences with a power of 80% and a 2-sided alpha level of 0.025 required a total sample of 120 patients. ResultsA total of 120 patients were randomized; 119 were eligible. Patient demographics, shown in the Table, were matched among the three groups:Standard Dose G N = 40High Dose G N = 40G + GM N = 39Age50 (20-71)50 (21-66)49 (22-69)Sex M:F26:1421:1916:23Disease-NHL19 (47.5%)20 (50.0%)17 (43.6%)-HD9 (22.5%)8 (20.0%)7 (17.9%)-Multiple Myeloma4 (10.0%)4 (10.0%)5 (12.8%)-Other8 (20.0%)9 (22.6%)9 (23.0%)Remission Status-CR1/PR15 (13.9%)5 (13.5%)8 (27.6%)-CR2/PR27 (19.4%)10 (27.0%)6 (20.7%)-IF/Ref24 (66.7%)22 (59.6%)15 (51.7%)# Prior Radiotherapy1087Median # of Prior Chemo Regimens2 (1-6)2 (1-6)2 (1-6)Median # of Total Cycles9 (4-22)10 (1-18)10 (4-34)Time from DX to Entry (months)21 (7-207)25 (9-295)23 (10-129)Baseline ANC K/μl3.0 (1.7-6.8)4.0 (1.6-10.7)3.7 (1.5-9.7)Baseline platelets K/μl213 (131-413)213 (84-358)206 (37-432)The % of patients collecting ≥2.5 × 106 CD34/kg was: standard G: 60%, high dose G: 57% (p = 1.0), G + GM: 41% (p = 0.1). Median CD34 collected in first mobilization were, 3.6 × 106/kg, 3.0 × 106/kg (p = 0.22) and 2.0 × 106/kg (p = 0.05) respectively in a median of 4, 4, and 5 aphereses (p = NS). Re-mobilization rates: standard G; 37.5%, high dose G: 35%; G + GM: 50% (p = NS). Total median CD34 collected from first and any second mobilizations were: standard G: 4.8 × 106/kg, high dose G: 3.9 × 106/kg, and G + GM: 3.5 × 106/kg. One patient in the standard G arm and 3 in high dose G did not proceed to transplant due to poor initial mobilization and progression in 2, and one each for progression or poor mobilization alone. There were no significant differences in median engraftment times: for ANC, 10, 11 and 15 days respectively for the standard G-, high dose G- and G + GM arms and for platelets, 11, 13 and 14 days respectively. The overall survivals @ the median f/u time of 37 months were 59.8%, 61.8% and 48.1% respectively (p = 0.272) for the three groups. The % primitive HSC (CD34+/CD33- and CD34+/CD38-) from the first mobilization were identical in the 3 patient groups. ConclusionsWe found no advantage to dose escalated G-CSF nor to the combination of G-CSF and GM-CSF to mobilize HSC for autotransplantation in heavily pre-treated patients. We also did not find higher numbers of more primitive CD34 subsets mobilized by these newer strategies. Alternative approaches, e.g. the combination of plerixifor + standard dose G-CSF (Stiff et al: BBMT; 15:249-56, 2009) would appear to be the preferred method of initial HSC mobilization for heavily pre-treated patients. DisclosuresStiff:Genzyme: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding.