scholarly journals Pipobroman therapy of polycythemia vera

Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 890-894 ◽  
Author(s):  
A Najman ◽  
J Stachowiak ◽  
Y Parlier ◽  
NC Gorin ◽  
G Duhamel
Keyword(s):  
Polycythemia Vera ◽  
Alkylating Agents ◽  
Maintenance Phase ◽  
Hematologic Malignancies ◽  
High Dose ◽  
Radioactive Phosphorus ◽  
Oncogenic Potential ◽  
Previously Treated ◽  
The Mean

Abstract Between 1971 and 1981, 74 patients with polycythemia vera were treated with pipobroman using a high-dose induction, low-dose maintenance regimen. Complete remission was achieved in 51 of 54 previously untreated patients (94.4%) and in 17 of 20 patients (85%) previously treated wih radioactive phosphorus (32 p) and busulfan. The earliest modifications were noted on day 16, and on the average, blood counts were normal by day 45. Thirty percent of the patients relapsed, the mean duration of the remission being 17.5 mo. Following recurrence pipobroman was consistently effective in the same doses but the mean duration of the next remissions was 10 mo. Transient leukopenia and thrombocytopenia occurred in 8% and 7% of patients, respectively, during initial phase, and anemia was noted in 3 patients. Macrocytosis was noted in 20% of patients during maintenance phase. Three cases of acute leukemia and 3 cases of osteomyelosclerosis were recorded, all occurring in patients who had previously received 32 p and/or busulfan. No hematologic malignancies were seen among patients treated with pipobroman alone; follow-up exceeded 6 yr for 20 patients and the median follow-up period was 3.6 yr. Pipobroman appears safer than other alkylating agents; it is as effective as 32 p and works more quickly. Longer follow-up will be required to evaluate the drug's oncogenic potential, which is still not known.

scholarly journals Pipobroman therapy of polycythemia vera

Blood ◽  
1982 ◽  
Vol 59 (5) ◽  
pp. 890-894 ◽  
Author(s):  
A Najman ◽  
J Stachowiak ◽  
Y Parlier ◽  
NC Gorin ◽  
G Duhamel
Keyword(s):  
Polycythemia Vera ◽  
Alkylating Agents ◽  
Maintenance Phase ◽  
Hematologic Malignancies ◽  
High Dose ◽  
Radioactive Phosphorus ◽  
Oncogenic Potential ◽  
Previously Treated ◽  
The Mean

Between 1971 and 1981, 74 patients with polycythemia vera were treated with pipobroman using a high-dose induction, low-dose maintenance regimen. Complete remission was achieved in 51 of 54 previously untreated patients (94.4%) and in 17 of 20 patients (85%) previously treated wih radioactive phosphorus (32 p) and busulfan. The earliest modifications were noted on day 16, and on the average, blood counts were normal by day 45. Thirty percent of the patients relapsed, the mean duration of the remission being 17.5 mo. Following recurrence pipobroman was consistently effective in the same doses but the mean duration of the next remissions was 10 mo. Transient leukopenia and thrombocytopenia occurred in 8% and 7% of patients, respectively, during initial phase, and anemia was noted in 3 patients. Macrocytosis was noted in 20% of patients during maintenance phase. Three cases of acute leukemia and 3 cases of osteomyelosclerosis were recorded, all occurring in patients who had previously received 32 p and/or busulfan. No hematologic malignancies were seen among patients treated with pipobroman alone; follow-up exceeded 6 yr for 20 patients and the median follow-up period was 3.6 yr. Pipobroman appears safer than other alkylating agents; it is as effective as 32 p and works more quickly. Longer follow-up will be required to evaluate the drug's oncogenic potential, which is still not known.

A Pilot Clinical Trial of Surgical Adjuvant Treatment with High-Dose 6S-Leucovorin/5-Fluorouracil and Radiation Therapy for High-Risk Rectal Carcinoma

1994 ◽  
Vol 80 (5) ◽  
pp. 335-338 ◽  
Author(s):  
Stefano Cascinu ◽  
Antonio Veraldi ◽  
Gian Paolo Foglietti ◽  
Roberto Ghiselli ◽  
Vittorio Saba ◽  
...  
Keyword(s):  
Radiation Therapy ◽  
High Risk ◽  
Rectal Carcinoma ◽  
Adjuvant Treatment ◽  
Randomized Trials ◽  
Dose Intensity ◽  
High Dose ◽  
Radiotherapy Alone ◽  
The Mean

Aims and background The study was performed to evaluate the feasibility of combining leucovorin (LV) with 5-fluorouracil (5FU) and radiation therapy as adjuvant treatment for high-risk rectal carcinoma. Methods Twenty-five patients with histologically proven adenocarcinoma of the rectum, at high-risk of recurrence after potentially curative resection (T3 NO, T any N1-2; MO), received 5FU (370 mg/m2) and 6S-LV (100 mg/m2) on days 1-5, 4 and 8 weeks after surgery. On treatment day 64, radiotherapy on the pelvis (50 Gy) was initiated. Finally, three further courses of 5FU/LV were given at intervals of 4 weeks beginning 28 days after the completion of radiotherapy. Results The treatment was generally well tolerated. We observed only 2 cases of grade III toxicity (diarrhea) during the third cycle of chemotherapy. No severe complications were recorded following the use of radiotherapy. The mean overall 5FU dose intensity was 92%. After a median follow-up of 24 months, 4 patients had relapsed (liver, lung, and pelvis, 2 cases). Conclusions The association of LV to 5FU and radiation therapy seems to be feasible, with acceptable toxicity. The advantage of this combination, in terms of recurrence rate and survival with respect to 5FU/radiotherapy alone, will have to be evaluated in randomized trials.

A phase I/II study of the selective phosphatidylinositol 3-kinase-delta (PI3Kδ) inhibitor, GS-1101 (CAL-101), with ofatumumab in patients with previously treated chronic lymphocytic leukemia (CLL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6518-6518 ◽  
Author(s):  
Richard R. Furman ◽  
Jacqueline Claudia Barrientos ◽  
Jeff Porter Sharman ◽  
Sven De Vos ◽  
John Leonard ◽  
...  
Keyword(s):  
Treated Patient ◽  
Alkylating Agents ◽  
Phase 1 ◽  
Single Agent ◽  
Hematologic Malignancies ◽  
Lymphocytic Leukemia ◽  
Combination Regimen ◽  
Highly Active ◽  
Previously Treated ◽  
Orally Bioavailable

6518^ Background: PI3Kδ is expressed in cells of hematopoietic origin where it regulates the survival and proliferation of malignant B-cells. GS-1101 is an orally bioavailable, small-molecule inhibitor that selectively targets PI3Kδ and is highly active in patients with hematologic malignancies. Methods: This Phase 1/2 study evaluated repeated 28-day cycles of GS‑1101 in combination with ofatumumab. GS-1101 (150mg BID) was co-administered with a total of 12 infusions of ofatumumab over 24 weeks (300mg initial dose either on Day 1 or Day 2 (relative to the first dose of GS-1101), followed 1 week later by 1,000mg weekly for 7 doses, followed 4 weeks later by 1,000mg every 4 weeks for 4 doses). Thereafter, each subjects received single-agent GS‑1101 as long as the subject was benefitting. Results: Accrual is complete with 21 subjects enrolled and 11 evaluable. Six subjects started ofatumumab treatment on Day 1 and 5 on Day 2. Median [range] age was 63 [54‑76] years. The majority (9/11; 82%) of patients had bulky adenopathy. The median [range] number of prior therapies was 3 [1‑6], including prior exposure to alkylating agents (10/11; 90%), rituximab (9/11; 82%), purine analogs (8/11; 72%), alemtuzumab (3/11; 28%) and/or ofatumumab (2/11;18%). At the data cutoff, the median [range] treatment duration was 5 [0‑7] cycles. Almost all subjects (9/11;82%) experienced marked and rapid reductions in lymphadenopathy within the first 2 cycles. The lymphocyte mobilization that is expected with PI3Kδ inhibition was significantly reduced in magnitude and duration and persisted past Cycle 1 in only 1 patient. Early follow up data support a favorable safety profile and confirm a lack of clinically significant myelosuppression. Elevated baseline levels of CCL3, CCL4, CXCL13, and TNFa were significantly reduced after 28 days of treatment. Conclusions: GS-1101/ofatumumab offers a well-tolerated noncytotoxic combination regimen with substantial activity in previously treated patient with bulky adenopathy. Data on the complete cohort of 21 subjects will be presented.

scholarly journals MON-096 Endocrine Complications Following Cancer Treatment in Survivors of Pediatric Solid Tumors: 18 Years’ Experience of a Single Academic Center

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Yena Lee ◽  
Arum Oh ◽  
Jin-Ho Choi ◽  
Han-Wook Yoo
Keyword(s):  
Cancer Treatment ◽  
Solid Tumors ◽  
High Dose ◽  
Pituitary Hormone ◽  
Hypergonadotropic Hypogonadism ◽  
Hematopoietic Stem ◽  
Pediatric Solid Tumors ◽  
The Mean ◽  
Endocrine Complications

Abstract Background: Survival rates of pediatric cancer have been significantly improved over recent decades because of advances in chemotherapy and radiotherapy. The endocrine consequences of cancer treatment have become the major medical issues in the childhood cancer survivors. This study was performed to investigate the long-term endocrine complications in survivors of pediatric solid tumors. Methods: From 2000 to 2018, 402 patients were diagnosed with solid tumors including hepatoblastoma (n = 72), neuroblastoma (n = 117), Wilms tumor (n = 57), Ewing sarcoma (n = 40), osteosarcoma (n = 65), and rhabdomyosarcoma (n = 51) in our institute. Among them, 96 patients (24%) were expired during the follow-up period. Growth profiles and endocrinologic findings were analyzed by retrospective chart review in 306 survivors of solid tumors. Results: The median age at diagnosis of primary cancer was 3 years (range, 0 month to 18 years). The mean treatment duration was 11.7 ± 12.6 months, and the mean follow-up duration after cancer treatment was 7.1 ± 4.8 years. Short stature,which was defined by height-SDS below -2.0, was found in 39 patients (12.7%) with the mean height-SDS of -2.59 ± 0.45. Primary hypothyroidism was detected in 19 patients (6.2%), and 15 of them were treated with radiotherapy or 131I-MIBG therapy due to the metastatic neuroblastoma. Sixteen patients (5.2%) developed hypergonadotropic hypogonadism, whereas three patients (1%) were diagnosed with central precocious puberty. Vitamin D deficiency and osteoporosis were found in 4 patients (1.3%) and 3 patients (1%), respectively. Primary adrenal insufficiency was found in one patient who underwent bilateral adrenalectomy because of bilateral neuroblastoma. One patient with rhabdomyosarcoma in the nasal cavity underwent high dose radiotherapy (50.4 Gy) around the tumor site, eventually leading to multiple pituitary hormone deficiency. In multivariable analysis, longer duration of treatment (≥24 months) was associated with the endocrine complications (OR = 3.94; CI 1.41-11.06) and hematopoietic stem cell transplantation was a major risk factor for endocrine complications (OR = 4.70; CI 2.14-10.29). Conclusions: Various endocrine complications can occur in survivors of solid tumors in children and adolescents caused by treatment modalities including surgery, chemotherapy, and radiotherapy, rather than the tumor itself. Lifetime monitoring is necessary to detect endocrine consequences such as growth retardation, hypergonadotropic hypogonadism, and thyroid dysfunctions.

scholarly journals Minimal fluoroscopic approaches and factors associated with radiation dose when high-definition mapping is used for supraventricular tachycardia ablation: insight from the CHARISMA registry

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
C La Greca ◽  
FM Cauti ◽  
A Piro ◽  
N Di Belardino ◽  
M Anselmino ◽  
...  
Keyword(s):  
Radiation Exposure ◽  
Supraventricular Tachycardia ◽  
Right Atrial ◽  
High Dose ◽  
Inverse Association ◽  
High Definition ◽  
Factors Associated ◽  
Mapping System ◽  
The Mean

Abstract Funding Acknowledgements Type of funding sources: None. Background Limited data exist on factors associated with radiation exposure during ablation procedures when a high definition mapping technology is used. Purpose To report factors associated with radiation exposure and data on feasibility and safety of a minimal fluoroscopic approach using the Rhythmia mapping system in supraventricular tachycardia (SVT) ablation procedures. Methods Consecutive patients indicated for arrhythmia ablation were enrolled in the CHARISMA study at 12 centers. We included in this analysis consecutive right-side procedures performed through a minimal fluoroscopy approach with the Rhythmia mapping system were analyzed. A 3D geometry of chambers of interest was reconstructed on the basis of the electroanatomic information taken from the mapping system. Fluoroscopy was used only if deemed necessary. The effective dose (ED) was calculated using accepted formula. For our purpose high dose exposure was defined as an ED greater than the median value of ED of the population exposed to radiation. Results This analysis included 325 patients (mean age = 56 ± 17 years, 57% male) undergoing SVT procedures (152 AVNRT, 116 AFL, 41 AP and 16 AT). During the study, 27481 seconds of fluoroscopy was used (84.6 ± 224 seconds per procedure), resulting in a mean equivalent ED of 1.1 ± 3.7 mSv per patient. The mean reconstructed RA volume was 99 ± 54 ml in a mean mapping time of 12.2 ± 7 min. The mean number of radiofrequency ablations (RFC) to terminate each arrhythmia was 9.4 ± 9 (mean RFC delivery time equal to 6.7 ± 6 min). 192 procedures (59.1%) were completed without any use of fluoroscopy; during the remaining 133 procedures (39.9%), 206.6 ± 313.4 seconds of fluoroscopy was used (median ED = 1.2 mSv). In a minority of the cases (n = 25, 7.7%) the fluoroscopy time was higher than 5 minutes (median ED = 6.5 mSv), whereas radiologic exposure time greater than 1 minute occurred in ninety cases (27.7%, median ED = 2.1 mSv). On multivariate logistic analysis adjusted for baseline confounders the RFC application time (OR = 1.0014, 95%CI: 1.0007 to 1.0022; p = 0.0001) was independently associated to an ED greater than 1.2 mSv, whereas female gender had an inverse association (0.54, 0.29 to 0.98; p = 0.0435). Acute success was reached in 97.8% of the cases. During a mean of 290.7 ± 169.6 days follow-up, no major adverse events related to the procedure were reported. Overall, the recurrence rate of the primary arrhythmia during follow-up was 2.5%. Conclusions In our experience, arrhythmias ablation through minimal fluoroscopy approach with the use of a novel ablation technology is safe, feasible, and effective in common right atrial arrhythmias. High-dose exposure occurred in a very limited number of cases, without any reduction of the safety and acute and long-term effectiveness profile.

scholarly journals Fractionated Gamma Knife radiosurgery for skull base meningiomas: a single-institution experience

2019 ◽  
Vol 46 (6) ◽  
pp. E8 ◽  
Author(s):  
Krishna C. Joshi ◽  
Alankrita Raghavan ◽  
Baha’eddin Muhsen ◽  
Jason Hsieh ◽  
Hamid Borghei-Razavi ◽  
...  
Keyword(s):  
Skull Base ◽  
Gamma Knife ◽  
Tumor Volume ◽  
Gamma Knife Radiosurgery ◽  
Cranial Neuropathy ◽  
High Dose ◽  
Perilesional Edema ◽  
The Mean ◽  
Skull Base Meningiomas

OBJECTIVEGamma Knife radiosurgery (GKRS) has been successfully used for the treatment of intracranial meningiomas given its steep dose gradients and high-dose conformality. However, treatment of skull base meningiomas (SBMs) may pose significant risk to adjacent radiation-sensitive structures such as the cranial nerves. Fractionated GKRS (fGKRS) may decrease this risk, but until recently it has not been practical with traditional pin-based systems. This study reports the authors’ experience in treating SBMs with fGKRS, using a relocatable, noninvasive immobilization system.METHODSThe authors performed a retrospective review of all patients who underwent fGKRS for SBMs between 2013 and 2018 delivered using the Extend relocatable frame system or the Icon system. Patient demographics, pre- and post-GKRS tumor characteristics, perilesional edema, prior treatment details, and clinical symptoms were evaluated. Volumetric analysis of pre-GKRS, post-GKRS, and subsequent follow-up visits was performed.RESULTSTwenty-five patients met inclusion criteria. Nineteen patients were treated with the Icon system, and 6 patients were treated with the Extend system. The mean pre-fGKRS tumor volume was 7.62 cm3 (range 4.57–13.07 cm3). The median margin dose was 25 Gy delivered in 4 (8%) or 5 (92%) fractions. The median follow-up time was 12.4 months (range 4.7–17.4 months). Two patients (9%) experienced new-onset cranial neuropathy at the first follow-up. The mean postoperative tumor volume reduction was 15.9% with 6 patients (27%) experiencing improvement of cranial neuropathy at the first follow-up. Median first follow-up scans were obtained at 3.4 months (range 2.8–4.3 months). Three patients (12%) developed asymptomatic, mild perilesional edema by the first follow-up, which remained stable subsequently.CONCLUSIONSfGKRS with relocatable, noninvasive immobilization systems is well tolerated in patients with SBMs and demonstrated satisfactory tumor control as well as limited radiation toxicity. Future prospective studies with long-term follow-up and comparison to single-session GKRS or fractionated stereotactic radiotherapy are necessary to validate these findings and determine the efficacy of this approach in the management of SBMs.

scholarly journals Evaluation of 0.2 µg/day fluocinolone acetonide (ILUVIEN) implant in a cohort of previously treated patients with diabetic macular oedema (DMO): a 36-month follow-up clinical case series

2020 ◽  
Vol 5 (1) ◽  
pp. e000484
Author(s):  
Muna Ahmed ◽  
Christine Putri ◽  
Hibba Quhill ◽  
Fahd Quhill
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Macular Oedema ◽  
Case Series ◽  
Diabetic Macular Oedema ◽  
Fluocinolone Acetonide ◽  
Previously Treated Patients ◽  
Previously Treated ◽  
The Mean

ObjectiveTo assess the real-world effectiveness and safety of single injection of a fluocinolone acetonide (FAc) implant in previously treated patients with recurrent diabetic macular oedema (DMO) over a 36-month follow-up period.Methods and AnalysisThis is a retrospective study conducted at a single ophthalmology department at the Royal Hallamshire Hospital, Sheffield, UK. Data were collected using electronic medical records to identify all patients treated with a FAc implant for DMO between March 2014 and November 2014, followed with a 36-month clinic follow-up. Outcomes measured included mean change in best-recorded visual acuity (BRVA) and central macular thickness (CMT) over the period of 36 months, treatment burden pre-implant and post-implant, and functional and anatomical responder rates.ResultsTwenty-six eyes (n=22 patients) were treated with single intravitreal FAc implant followed with 36 months of follow-up. At 24 and 36 months, 86.4% and 75.0% of patients maintained or gained vision post-FAc implant in routine clinical practice. The mean BRVA increased from 41.8 to 54.6 letters at month 24 and 45.8 letters at month 36, with 50.0% and 33.3% of patients achieving a ≥15 letter improvement at months 24 and 36, respectively. The mean CMT reduced from 600.8 µm at baseline to 351.0 µm and 392.5 µm at months 24 and 36, respectively. Overall, a mean of one treatment every 13.33 months post-FAc implant (vs 3.24 months pre-FAc implant) was reported. Eleven eyes had an increased intraocular pressure of ≥10 mm Hg and 12 eyes had an increase to ≥25 mm Hg from baseline.ConclusionThese results further support the effectiveness and safety of FAc implant in previously treated patients with persistent or recurrent DMO in a real-world clinical practice.

scholarly journals Long-term follow-up of patients with chronic lymphocytic leukemia treated with fludarabine as a single agent

Blood ◽  
1993 ◽  
Vol 81 (11) ◽  
pp. 2878-2884 ◽  
Author(s):  
MJ Keating ◽  
S O'Brien ◽  
H Kantarjian ◽  
W Plunkett ◽  
E Estey ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Clinical Response ◽  
Alkylating Agents ◽  
Single Agent ◽  
Response To Therapy ◽  
Lymphocytic Leukemia ◽  
Strongly Correlated ◽  
Prior Therapy ◽  
Previously Treated

Abstract The clinical response and survival of 113 patients with at least 3-year follow-up after treatment with fludarabine as a single agent for chronic lymphocytic leukemia has been evaluated. Seventy-eight patients were previously treated and 35 were untreated. The response to therapy and survival were strongly correlated with the degree of previous therapy, the stage of disease, and whether or not the patients were refractory to alkylating agents. Other characteristics associated with survival were the age of the patient and the serum albumin level at the start of therapy. The median time to progression of responders who had not received prior therapy was 33 months and was 21 months for previously treated patients. Survival after progression of disease was also strongly correlated with the degree of prior therapy. No successful salvage regimen after initial fludarabine therapy was shown for patients refractory to alkylating agents, although fludarabine achieved further remissions in patients who had received fludarabine as their initial treatment or were not refractory to alkylating agents. The morbidity of patients in unmaintained remission on discontinuation of fludarabine was low, with less than one episode of infection per patient-year at risk. The morbidity during this time was correlated with clinical response and whether the patients had received prior therapy. Although fludarabine is a very effective cytoreductive regimen, most patients, including those who achieved true complete remissions, will have recurrent disease. Longer follow-up and comparative trials are required before the effect of fludarabine on survival is shown.

Hyperglycemia and obesity in patients (pts) with acute lymphoblastic leukemia (ALL): Association with prevalence, response, and survival

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7074-7074
Author(s):  
K. D. Vu ◽  
V. R. Lavis ◽  
S. Strom ◽  
S. H. Faderl ◽  
M. Konopleva ◽  
...  
Keyword(s):  
Cox Regression ◽  
Lymphoblastic Leukemia ◽  
Univariate Analysis ◽  
Retrospective Chart Review ◽  
Hematologic Malignancies ◽  
Serum Glucose ◽  
High Dose ◽  
Baseline Serum ◽  
Significant Difference ◽  
The Mean

7074 Increasing evidence suggests associations between obesity, diabetes and/or hyperglycemia (DM/HG) and solid tumors. Less is known about the relationship of these metabolic factors to the hematologic malignancies. To determine the prevalence of DM/HG and obesity in pts with ALL and whether these are predictors of response and survival, we conducted a retrospective chart review of 299 pts with newly diagnosed ALL, who were evaluated at our institution between November 1999 and May 2005 and received hyper-CVAD therapy: fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and high-dose cytarabine. Median age was 43 yrs (range 15–83). Sixty-one percent of pts were male, and 39% female. Seventy-four percent had a diagnosis (dx) of precursor B cell ALL (22% Ph+), 18% Burkitt's ALL, 6% lymphoblastic lymphoma, 2% other. Prior to therapy, the overall prevalence of DM/HG (diabetes based on reported dx prior to ALL-dx, and hyperglycemia based on baseline serum glucose ≥200 mg/dL) was 16%. Pts with DM/HG were significantly older than those without DM/HG (median age 57 yrs vs. 40 yrs, p<0.001). Complete remission (CR) rate and the CR duration (CRD) were similar in the DM/HG vs. non-DM/HG group. However, the mean CRD was 80 wks in the HG separately group and 121 wks in the non-HG group (p=0.04). The mean CRD was 102 wks in the obese pts and 124 wks in the non-obese pts (p=.04). In univariate analysis, DM/HG, obesity, and older age were associated with shorter overall survival (OS). Mean OS of pts with DM/HG was 134 vs. 194 wks for pts without DM/HG, (p=0.2). Mean OS of obese pts was 136 vs. 199 wks for non-obese pts, (p=0.01). In a multivariable Cox regression model, the only factors that remained significant for survival were age, obesity, and white blood cell count (WBC). There was no significant difference in OS by leukemia diagnosis. In conclusion, the prevalence data suggests that DM/HG may be involved in the development of ALL. However, DM/HG has no impact on survival, probably because of its strong correlation with age. The association of obesity with shorter OS warrants further investigation. No significant financial relationships to disclose.

Palifermin in Patients with Hematological Malignancies Undergoing Autologous Hematopoietic Stem Cell Transplantation (HSCT): The Italian Early Access Program (EAP).

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5236-5236
Author(s):  
Laura M. Cavagna ◽  
Gaetano Bonifacio ◽  
Emanuele Angelucci ◽  
Alessandro Fanni ◽  
Giuseppe Milone ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Adverse Events ◽  
Interim Analysis ◽  
Hematological Malignancies ◽  
Hematologic Malignancies ◽  
World Health ◽  
High Dose ◽  
Hematopoietic Stem ◽  
The Mean

Abstract Oral mucositis (OM) is an acute, severe and often dose-limiting toxicity in patients undergoing HSCT. OM significantly affects functional status and patients’ quality of life; however no effective therapy was available for this condition. Palifermin (Kepivance®) is a human keratinocyte growth factor (KGF) produced by recombinant DNA technology. KGF binds to its receptor on epithelial cells, stimulating their proliferation, differentiation, and migration. Palifermin has been shown to decrease the incidence and duration of severe OM in patients with hematologic malignancies receiving myelotoxic therapy and HSCT. In Italy, compassionate use protocols are considered EAP and are regulated by a decree issued by the Ministry of Health (MoH) on May 8th 2003. The objective of the Decree is to ensure that patients have access to experimental therapies outside clinical trials, when no valid therapeutic alternative exists. Approval is granted in case of serious or rare diseases or life-threatening conditions. After Ethical Committee (EC) approval and notification to MoH, the drug can be supplied in response to an unsolicited request from a physician. The drug is then administered under the physician’s direct responsibility. During EAP, the Decree allows collection of the patient’s data similar to an observational trial. From July 2005 through July 2006 a total of 26 centers have requested the drug and obtained approval from local EC. Each center collected the following data on a case report form: vital signs, disease status and treatment, palifermin administration, mucositis, analgesic use, parenteral supplementation, common laboratory tests and duration of hospitalization. A total of 175 adults patients with hematological malignancies treated with autologous SCT participated in the EAP. In an interim analysis, data from 41 patients (24 men; 17 women; median age 52.44) were analyzed. The most common diagnoses were multiple myeloma (MM) (n=16) and non-Hodgkin lymphoma (NHL) (n=15). Conditioning therapy and supportive care were administered according to standard institutional practice (high-dose melphalan for MM and the BEAM regimen for NHL). Palifermin 60 mcg/kg/day was given intravenously on 3 consecutive days before the conditioning regimen and on 3 days starting on the day of stem cell infusion. OM was evaluated daily for 28 days after transplantation or until severe OM resolution using the five-grade World Health Organization (WHO) oral-toxicity scale. Safety was assessed on the basis of the incidence of adverse events. The incidence of severe OM (Grade 3–4) was 17% and the mean duration was 2.2 ± 3.5 days (CI, 1.1–3.3) in patients with OM Grade 0–4 while in patients with OM G3-4 the mean duration was 6.9 ± 2.5 (CI, 4.5–9.2). Adverse events (mainly rash, pruritus, erythema, mouth and tongue disorders, and taste alteration) were mild to moderate in severity and were transient. The frequency of adverse events was consistent with those observed in clinical trials. In conclusion, the Italian EAP experience with palifermin suggested that results were consistent with those of pivotal studies in patients with hematologic malignancies undergoing HSCT. From the results of the interim analysis of the Italian EAP, the use of palifermin in this setting appears to be feasible and was widely accepted by participating physicians and patients.

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