Prolonged progression-free survival in patients with chronic lymphocytic leukemia receiving granulocyte colony-stimulating factor during treatment with fludarabine, cyclophosphamide, and rituximab

Introduction The metastatic pancreatic adenocarcinoma clinical trial (MPACT) trial established gemcitabine (gem) and nab-paclitaxel (nab) as a standard treatment for pancreatic cancer utilizing granulocyte colony-stimulating factors to manage neutropenia. This was a challenge for jurisdictions that do not use granulocyte colony-stimulating factors in palliative settings. We developed dosage guidelines to dose modify gem and nab without granulocyte colony-stimulating factors. We undertook a retrospective review to determine the efficacy and safety of these dose adjustment guidelines in the real world. Methods A multi-centered, retrospective chart review was performed on pancreatic patients between December 1, 2014, and August 21, 2018. Provincial electronic medical health records were reviewed. Using Log-rank statistics we determined the patient's progression-free survival and overall survival. Results Of 248 patients, 209 met patient selection criteria. Patients were excluded if they were lost to follow-up, on gem alone prior to nab/gem combination therapy or did not receive nab or gem. Patients who received nab/gem as first-line therapy had a median progression-free survival of 6.3 months (95% CI, 5.1–7.4), and median overall survival of 11.1 months (95% CI, 9.5–12.8). Those who received gem/nab in the second line had a median progression-free survival of 4.6 months (95% CI, 2.8–6.5), and median overall survival of 19.3 months (95% CI, 12.6–26.0). Conclusions The patient’s progression-free survival and overall survival taking nab/gem using our dose modification algorithm were equivalent or superior to the MPACT trial's progression-free survival and overall survival. Gem/nab can be given by our dose modification scheme without granulocyte colony-stimulating factor.

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Treatment of advanced, relapsed chronic lymphocytic leukemia (CLL) with fludarabine, miroxantrone and cyclophosphamide combination therapy with or without granulocyte colony stimulating factor (G-CSF)

http://isrctn.org/> ◽

10.1186/isrctn31486124 ◽

2013 ◽

Author(s):

Michael Hallek

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Combination Therapy ◽

Lymphocytic Leukemia ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor ◽

Factor G

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Fludarabine and granulocyte colony-stimulating factor (G-CSF) in patients with chronic lymphocytic leukemia

Leukemia ◽

10.1038/sj.leu.2400816 ◽

1997 ◽

Vol 11 (10) ◽

pp. 1631-1635 ◽

Cited By ~ 41

Author(s):

S O’Brien ◽

H Kantarjian ◽

M Beran ◽

C Koller ◽

M Talpaz ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Lymphocytic Leukemia ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor ◽

Factor G

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Successful treatment of partial graft failure after matched unrelated donor stem cell transplantation by a combination of ancestim (stem cell factor) and granulocyte colony stimulating factor in a patient with heavily pre-treated chronic lymphocytic leukemia

Leukemia & Lymphoma ◽

10.1080/10428190802304958 ◽

2008 ◽

Vol 49 (10) ◽

pp. 2015-2017 ◽

Cited By ~ 1

Author(s):

Sixten Körper ◽

Gero Hütter ◽

Wolfgang Blau ◽

Olga Blau ◽

Hubert Schrezenmeier ◽

...

Keyword(s):

Stem Cell ◽

Chronic Lymphocytic Leukemia ◽

Stem Cell Factor ◽

Graft Failure ◽

Lymphocytic Leukemia ◽

Unrelated Donor ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Matched Unrelated Donor ◽

Stimulating Factor

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The Granulocyte Colony-Stimulating Factor (G-CSF)/G-CSF Receptor (G-CSFR) System in B-Cell Chronic Lymphocytic Leukemia

Leukemia & Lymphoma ◽

10.3109/10428199709059680 ◽

1997 ◽

Vol 27 (3-4) ◽

pp. 239-246 ◽

Cited By ~ 4

Author(s):

Anna Corcione ◽

Paola Tasso ◽

Vito Pistoia

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

Lymphocytic Leukemia ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Stimulating Factor ◽

Cell Chronic Lymphocytic Leukemia ◽

Factor G

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Expression of granulocyte colony-stimulating factor and granulocyte colony-stimulating factor receptor genes in partially overlapping monoclonal B-cell populations from chronic lymphocytic leukemia patients

Blood ◽

10.1182/blood.v87.7.2861.bloodjournal8772861 ◽

1996 ◽

Vol 87 (7) ◽

pp. 2861-2869 ◽

Cited By ~ 14

Author(s):

A Corcione ◽

MV Corrias ◽

S Daniele ◽

S Zupo ◽

M Spriano ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

B Cell ◽

B Lymphocytes ◽

Cell Suspensions ◽

Lymphocytic Leukemia ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Cell Fractions ◽

Stimulating Factor

B lymphocytes were purified from the peripheral blood of 30 B-cell chronic lymphocytic leukemia (B-CLL) patients and tested for the ability to produce granulocyte colony-stimulating factor (G-CSF) in vitro. Fifteen Staphylococcus aureus Cowan I (SAC)-stimulated, but not unstimulated, B-cell suspensions produced G-CSF in short-term cultures. Accordingly, G-CSF mRNA was detected only in SAC-stimulated B cells. Five CLL B-cell fractions that released G-CSF following exposure to SAC were also incubated with CD40 or anti-mu antibodies in the presence or absence of recombinant (r) interleukin-2 (IL-2) or IL-4. The 5 cell suspensions produced G-CSF only on culture with CD40 monoclonal antibody in combination with rIL-2 or rIL-4. CD5+ B lymphocytes, which represent the normal counterparts of most B-CLL proliferations, did not produce G-CSF under any of the above culture conditions. G-CSF produced by leukemic B lymphocytes was biologically active, because conditioned media of SAC-stimulated cells supported the in vitro growth of myeloid colonies from normal bone marrow progenitors. The colony stimulating activity of CLL B-cell supernatants was ascribed to both G-CSF and granulocyte-macrophage colony stimulating factor. G-CSF receptors (G- CSFRs) were detected on freshly isolated B lymphocytes from 7 of 11 B- CLL patients; 5 of these cell suspensions produced G-CSF in culture, whereas 2 did not. rG-CSF rescued 3 of the 7 G-CSFR+ cell fractions from spontaneous apoptosis but had no effect on their in vitro proliferation.

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Randomized Phase III Trial of High–Dose-Intensity Methotrexate, Vinblastine, Doxorubicin, and Cisplatin (MVAC) Chemotherapy and Recombinant Human Granulocyte Colony-Stimulating Factor Versus Classic MVAC in Advanced Urothelial Tract Tumors: European Organization for Research and Treatment of Cancer Protocol No. 30924

Journal of Clinical Oncology ◽

10.1200/jco.2001.19.10.2638 ◽

2001 ◽

Vol 19 (10) ◽

pp. 2638-2646 ◽

Cited By ~ 410

Author(s):

C. N. Sternberg ◽

P. H.M. de Mulder ◽

J. H. Schornagel ◽

C. Théodore ◽

S. D. Fossa ◽

...

Keyword(s):

Dose Intensity ◽

Progression Free Survival ◽

Phase Iii ◽

High Dose ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Free Survival ◽

Overall Response ◽

Stimulating Factor ◽

High Dose Intensity

PURPOSE: This randomized trial evaluated antitumor activity of and survival asociated with high–dose-intensity chemotherapy with methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) plus granulocyte colony-stimulating factor (HD-MVAC) versus MVAC in patients with advanced transitional-cell carcinoma (TCC). PATIENTS AND METHODS: A total of 263 patients with metastatic or advanced TCC who had no prior chemotherapy were randomized to HD-MVAC (2-week cycles) or MVAC (4-week cycles). RESULTS: Using an intent-to-treat analysis, at a median follow-up of 38 months, on the HD-MVAC arm there were 28 complete responses (CRs) (21%) and 55 partial responses (PRs) (41%), for an overall response of 62% (95% confidence interval [CI], 54% to 70%). On the MVAC arm, there were 12 CRs (9%) and 53 PRs (41%), for an overall response of 50% (95% CI, 42% to 59%). The P value for the difference in CR rate was .009; and for the overall response, it was .06. There was no statistically significant difference in survival (P = .122) or time to progression (P = .114). Progression-free survival was significantly better with HD-MVAC (P=.037; hazard ratio .75; 95% CI .58 to .98). The median progression-free survival time was 9.1 months on the HD-MVAC arm versus 8.2 months on the MVAC arm. The 2-year progression-free survival rate was 24.7% for HD-MVAC (95% CI, 17.1% to 32.3%) versus 11.6% for MVAC (95% CI, 5.9% to 17.4%). CONCLUSION: With HD-MVAC, it was possible to deliver twice the doses of cisplatin and doxorubicin in half the time, with fewer dose delays and less toxicity. Although a 50% difference in median overall survival was not detected, a benefit was observed in progression-free survival, CR rates, and overall response rates with HD-MVAC.

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Phase II Trial of Neoadjuvant Vincristine, Ifosfamide, and Doxorubicin With Granulocyte Colony-Stimulating Factor Support in Children and Adolescents With Advanced-Stage Nonrhabdomyosarcomatous Soft Tissue Sarcomas: A Pediatric Oncology Group Study

Journal of Clinical Oncology ◽

10.1200/jco.2005.03.209 ◽

2005 ◽

Vol 23 (18) ◽

pp. 4031-4038 ◽

Cited By ~ 69

Author(s):

Alberto S. Pappo ◽

Meenakshi Devidas ◽

Jessee Jenkins ◽

Bhaskar Rao ◽

Robert Marcus ◽

...

Keyword(s):

Soft Tissue ◽

Children And Adolescents ◽

Response Rate ◽

Survival Rates ◽

Soft Tissue Sarcomas ◽

Progression Free Survival ◽

Granulocyte Colony Stimulating Factor ◽

Colony Stimulating Factor ◽

Free Survival ◽

Stimulating Factor

Purpose To describe the response rate and survival of children and adolescents with unresected or metastatic nonrhabdomyosarcomatous soft tissue sarcomas (NRSTS) treated with vincristine, ifosfamide, and doxorubicin. Patients and Methods Between September 1996 and June 2000, 39 eligible patients received vincristine (1.5 mg/m2 weekly for 13 doses), ifosfamide (3 g/m2 daily for 3 days every 3 weeks for seven cycles), doxorubicin (30 mg/m2 daily for 2 days for six cycles), and mesna (750 mg/m2 for four doses after ifosfamide). Granulocyte colony-stimulating factor was administered daily (5 μg/kg) after each cycle of chemotherapy. Radiotherapy was administered from weeks 7 through 12. Results The median patient age at diagnosis was 11.7 years; the most common primary tumor site was lower extremity (36%); and synovial sarcoma was the predominant histology. More than three fourths of all tumors were 5 cm or greater at their largest diameters. The overall objective combined partial and complete response rate was 41% (95% CI, 25.7% to 56.7%). The estimated 3-year overall survival and progression-free survival rates (± standard deviation) for eligible patients were 59% ± 8.2% and 43.6% ± 7%, respectively. Patients with clinical group III disease had significantly better 3-year and progression-free survival rates compared with patients who presented with metastatic disease. Conclusion The vincristine, ifosfamide, and doxorubicin regimen was moderately active against pediatric NRSTS. Patients with synovial sarcoma had higher response rates than other patients, and patients with unresected disease had improved outcomes. Patients with metastatic disease continue to fare poorly, and newer approaches are indicated for these patients.

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