Biomedical subjects

R Mick

Publications and source records attributed to R Mick.

At least 91 records · Page 5Linked to original sources

PubMed1993

Source of stem cell rescue: bone marrow versus peripheral blood progenitors.

Sustained hematopoiesis can be restored after dose-intensive chemotherapy utilizing stem cells from either bone marrow and/or peripheral blood. Numerous reports have demonstrated the effectiveness of peripheral blood progenitors (PBPC) in restoring hematopoiesis. Here, we review data comparing the recovery among patients rescued with various stem cell sources after dose-intensive therapy. PBPC used alone or to augment autologous bone marrow to achieve timely hematopoietic recovery after dose-intensive therapy can result in shortened hospital stays, decreased transfusion requirements, and antibiotic usage. This will lead to increased application of dose-intensive therapy either singly or in multiple courses to treat various malignancies.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1993

5-Fluorouracil, hydroxyurea and escalating doses of iododeoxyuridine with concomitant radiotherapy for malignant gliomas: a clinical and pharmacologic analysis.

BACKGROUND: Iododeoxyuridine (IUdR) is a known radiation enhancer, and interacts biochemically with 5-fluorouracil (5-FU) and hydroxyurea (HU). PATIENTS AND METHODS: IUdR was added to the previously studied regimen of continuous infusion 5-FU at 300 mg/m2/day for 5 days, HU 500 mg every 12 hours for 11 doses and radiotherapy 200 cGy/day for 5 days, all administered for 7 consecutive weeks to patients with malignant glioma. IUdR was administered as 5-day continuous intravenous infusion during weeks 1 and 4. The IUdR dose was changed in cohorts of patients. IUdR plasma concentrations were determined during weeks 1 and 4, and IUdR incorporation into the DNA of granulocytes was measured on weeks 2 and 5. RESULTS: Two patients treated at the initial IUdR dose of 500 mg/m2/day developed grade 3 or 4 myelosuppression and mucositis. Additional dose levels of IUdR tested were 250 mg/m2/day and 125 mg/m2/day; at the latter dose, severe or life-threatening toxicity was seen in only 3 of 8 patients treated. IUdR incorporation into DNA of granulocytes was 10.5(+/- 2.3)% at an IUdR dose of 500 mg/m2/day but decreased to 0.76(+/- 0.3)% at 125 mg/m2/day. Similarly, IUdR plasma concentrations decreased from 436 (+/- 114) ng/ml to 99 (+/- 29) ng/ml. CONCLUSIONS: The addition of IUdR to 5-FU and HU results in significant systemic toxicity necessitating limitation of the IUdR dose to 125 mg/m2/day. There is a significant biochemical interaction between IUdR, 5-FU and HU leading to increased IUdR incorporation into DNA and to substantial clinical toxicity. Further clinical studies to exploit this interaction at more feasible schedules may be useful.

Adult↗

PubMed1993

Cisplatin, fluorouracil, and leucovorin augmented by interferon alfa-2b in head and neck cancer: a clinical and pharmacologic analysis.

PURPOSE: To increase the activity of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) through further biochemical modulation and study the pharmacologic interaction of 5-FU and interferon alfa-2b (IFN). PATIENTS AND METHODS: Escalating doses of IFN (0.5 to 4.0 x 10(6) U/m2/d x 6) were added to cisplatin 100 mg/m2, continuous infusion 5-FU 800 or 640 mg/m2/d x 5, and leucovorin 100 mg orally every 4 hours. Forty-eight previously untreated patients with locoregionally advanced head and neck cancer received up to three cycles of PFL-IFN. RESULTS: Twenty-one patients were treated during a phase I cohort study. Dose-limiting mucositis was seen with 800 mg/m2/d of 5-FU and 0.5 x 10(6) U/m2/d of IFN. After decreasing the 5-FU dose to 640 mg/m2/d, the maximally tolerated dose (MTD) of IFN was 2.0 x 10(6) U/m2/d. Mucositis and myelosuppression were dose-limiting. Of 34 patients treated at this MTD, 56% (95% confidence interval, 39% to 73%) had a complete remission. There was no correlation between 5-FU clearance and IFN dose. Pharmacodynamic analyses at the MTD showed that older age, female sex, and higher 5-FU area under the time versus concentration curve (AUC) were associated with lower nadir counts and/or increased mucositis. Seven patients with diabetes mellitus had significantly increased myelosuppression, serum creatinine, hypocalcemia, higher 5-FU concentrations, and lower 5-FU clearance compared with nondiabetics. CONCLUSION: The recommended doses for PFL-IFN are 640 mg/m2/d for 5-FU and 2.0 x 10(6) U/m2/d for IFN. Sex, age, 5-FU AUC, and diabetes mellitus may have an impact on the pharmacodynamics of this regimen.

Adolescent↗

PubMed1992

Clinical, morphologic, and cytogenetic characteristics of 26 patients with acute erythroblastic leukemia.

We have performed a retrospective analysis of the clinical, morphologic, and cytogenetic findings in 26 patients diagnosed between January 1969 and September 1991 with acute erythroblastic leukemia de novo (EL or AML-M6). Clonal chromosomal abnormalities were found in 20 (77%) patients (95% confidence interval [CI], 61% to 93%). Loss of all or part of the long arm (q) of chromosomes 5 and/or 7 was observed in 17 (65%) patients (95% CI, 47% to 83%). In addition, the karyotypes were often complex, with multiple abnormalities and subclones. Among the remaining nine patients, six had a normal karyotype and one each had trisomy 8, t(3;3), or t(3;5). The overall frequency of abnormalities of chromosomes 5 and/or 7 observed in our M6 patients is similar to that observed in our patients with therapy-related acute myeloid leukemia (t-AML; 99 of 129 patients, 77%), but substantially higher than that noted in our other patients with AML de novo (French-American-British [FAB] subtypes M1-M5: 52 of 334 patients, 16%). Our M6 patients with abnormalities of chromosomes 5 and/or 7 were older and had a shorter median survival (16 v 77 weeks [P = .005]) than did the M6 patients without these abnormalities. We found no correlation between morphologic features and either cytogenetic abnormalities or clinical outcome. Of note was the finding that the percentage of myeloblasts, which may account for only a small fraction of the total marrow elements when the revised FAB criteria are applied, had no bearing on prognosis. We conclude that acute erythroblastic leukemia, when defined by morphologic criteria, consists of two distinctive subgroups: one group tends to be older, has complex cytogenetic abnormalities, especially of chromosomes 5 and/or 7, and shares biologic and clinical features with t-AML; the other group, with simple or no detectable cytogenetic abnormalities, has a more favorable prognosis when treated with intensive chemotherapy.

Adolescent↗

PubMed1992

Occurrence of p53 gene deletions and human papilloma virus infection in human head and neck cancer.

Little is known regarding the molecular genetic events in head and neck carcinoma. Epidemiological evidence suggests that both alcohol and tobacco use are related to the development of these neoplasms, and viral infections have also been postulated to play a role in some tumors. Loss of p53 tumor suppressor gene function has been found in many malignancies and can occur through either gene mutation or by interaction with the E6 protein of oncogenic human papilloma viruses (HPV). Because the mucosal surfaces of the head and neck are exposed to mutagens and HPVs, we studied DNA derived from 30 stage I-IV squamous cell carcinomas of the head and neck (9 primary tumors and 21 early passage cell lines) for p53 gene mutations as well as for the presence of oncogenic HPV DNA. Exons 2 through 11 of the p53 gene were examined using single strand conformation polymorphism analysis followed by direct genomic sequencing of all variants. HPV detection was done using polymerase chain reaction amplification with HPV E6 region type specific primers as well as L1 region degenerate ("consensus") primers; HPV type was determined by restriction fragment length polymorphism analysis of the amplified fragment as well as by Southern blotting of genomic DNA. Sixteen of 30 tumors (53%) had p53 mutations and oncogenic HPV DNA was detected in 3 of 30 (10%) tumors, none of which had p53 mutations. The p53 mutational spectrum observed was characterized by equal frequencies of transversions (6 of 16), transitions (5 of 16), and deletions (5 of 16). This distribution of mutations differs from the spectrum of p53 mutation reported in esophageal (P = 0.05) and lung (P = 0.02) cancers, two other tobacco associated neoplasms. A previously undescribed clustering of 3 mutations at codon 205 was also observed. A trend toward a shorter time to tumor recurrence after treatment was noted for those patients with tumors exhibiting p53 gene mutations, and no relationship between p53 mutations and tumor stage or node status was noted. Alteration in p53 gene function appears common in head and neck cancer, and the mutational spectrum observed may reflect the role of different mutagens or mutagenic processes than those responsible for the p53 mutations in lung and esophageal neoplasms.

Alcohol Drinking↗

PubMed1992

Favorable long-term survival following induction chemotherapy with cisplatin, fluorouracil, and leucovorin and concomitant chemoradiotherapy for locally advanced head and neck cancer.

BACKGROUND: The majority of patients with head and neck cancer die of locoregional recurrence of disease following surgery and/or radiotherapy. PURPOSE: Our purpose was to administer induction chemotherapy, perform surgery, and administer concomitant chemoradiotherapy in rapid sequence and to evaluate their impact on locoregional and distant tumor control. METHODS: Sixty-four patients with previously untreated, locoregionally advanced head and neck cancer received two cycles of cisplatin, bleomycin, and methotrexate (PBM) (33 patients) or cisplatin, fluorouracil (5-FU), and leucovorin (PFL) (31 patients). PFL was given to patients who were unable to receive bleomycin. Local therapy consisted of surgery and/or concomitant chemoradiotherapy with 5-FU, hydroxyurea, leucovorin, and radiotherapy (FHX-L), all administered every other week. RESULTS: Complete and overall induction response rates were 21% and 79%, respectively, for PBM and 29% and 81%, respectively, for PFL. At completion of local therapy, 81% of the patients were disease-free. With a median follow-up of 35 months, the median survival and time to progression are 22 and 17 months, respectively, for PBM and have not been reached for PFL. Locoregional recurrence of disease is 30% for PBM and 26% for PFL. Distant disease progression is 24% for PBM and only 3% for PFL. CONCLUSIONS: The sequencing of induction chemotherapy and concomitant chemoradiotherapy is feasible and results in a high local control rate and in an encouraging survival rate with PFL. The high distant failure (i.e., outside the head and neck area) rate of PBM suggests insufficient systemic activity for that regimen. IMPLICATIONS: Concomitant FHX-L chemoradiotherapy may improve regional control rates of advanced head and neck cancer. Effective systemic therapy may be needed to control systemic micrometastases. PFL, but not PBM, appears to be suitable to accomplish that goal.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1992

5-Fluorouracil, leucovorin, hydroxyurea, and escalating doses of continuous-infusion cisplatin with concomitant radiotherapy: a clinical and pharmacologic study.

Cisplatin (CDDP), 5-fluorouracil (5-FU), and hydroxyurea (HU) have individually demonstrated activity against several solid tumors, act synergistically with each other in vitro, and may act as radiation sensitizers. Therefore, we designed a phase I study to determine the maximally tolerated dose of cisplatin as given in addition to our previously described combination of 5-FU, HU, and concomitant radiotherapy (XRT). Patients exhibiting advanced solid tumors requiring palliative XRT were eligible. The regimen consisted of 1 g HU given p.o.b.i.d. on days 1-5, 600 mg/m2 5-FU given i.v. daily by continuous infusion (c.i.) on days 1-5, escalating doses of cisplatin starting at 10 mg/m2 daily given by c.i. on days 1-5, and involved-field XRT carried out on days 1-5. The cycle was repeated every 14 days until the target XRT dose had been reached. In all, 19 patients were entered at the first dose level, and cumulative grade 3-4 myelosuppression was seen in 16 subjects. As no dose escalation was feasible, the chemotherapy was subsequently altered by using the above regimen for cycles 1, 3, 5, and 7 and substituting the less myelosuppressive regimen of 1 g HU given p.o.b.i.d. on days 1-5, 400 mg/m2 5-FU given i.v. daily by c.i., and 100 mg leucovorin given p.o.4 h on days 1-5 for cycles 2, 4, and 6. On this alternating program, 28 patients were treated with escalating doses of CDDP. The dose-limiting toxicity was again myelosuppression, which was prohibitive at a CDDP dose of 20 mg/m2 daily. In the final phase of the protocol, 30 subjects were treated with the above alternating-cycle regimen at a CDDP dose of 20 mg/m2 daily and a decreased HU dose of 500 mg p.o.b.i.d. in an attempt to circumvent the myelosuppression associated with this dose of CDDP. Although severe acute toxicity (cycles 1 and 2) was observed less frequently, cumulative toxicity (all cycles) remained pronounced. The other major toxicity encountered was mucositis, which was particularly pronounced in patients receiving radiation to the head and neck and following leucovorin-containing cycles. Plasma concentrations of free platinum did not correlate with the CDDP dose, possibly due to the narrow range of doses given. Pharmacodynamic modeling demonstrated that the CDDP dose and the HU dose were associated with leukopenia. Antitumor activity was demonstrated in a number of solid tumors particularly non-small-cell lung cancer and head and neck cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

PubMed1992

Neoadjuvant PFL augmented by methotrexate and piritrexim followed by concomitant chemoradiotherapy for advanced head and neck cancer: a feasible and active approach.

To increase the complete remission (CR) rate achieved with two cycles of cisplatin, continuous infusion fluorouracil (5-FU) and oral leucovorin (PFL) we added two antifolate drugs, methotrexate (MTX) and the lipophilic piritrexim (PTX), to the combination (PFL-MP). Twenty-eight patients with previously untreated Stage IV squamous cell carcinoma of the head and neck received 2 cycles of cisplatin 100 mg/m2 on day 1 followed by a 5-day continuous infusion of 5-FU at 800 mg/m2/day and 100 mg of leucovorin administered orally every 4 hours. MTX was administered at 40 mg/m2 IV on day 15 and PTX at 75 mg orally twice daily on days 22 to 26, with cycle 2 starting on day 36. After 2 of the first 5 patients had tumor progression between days 15 and 35, the regimen was intensified to MTX 50 mg/m2, PTX 100 mg twice daily and a cycle duration of 28 days. Local therapy consisted of surgery and/or radiotherapy with concomitant 5-FU and hydroxyurea (FHX) administered every other week. Eleven patients (39%, 95% confidence intervals 21-57%) had a CR, 9 (32%) had a PR, and four patients had no response. Four patients were unevaluable for response to PFL-MP. Patients with poor performance status or N3 disease were less likely to achieve a CR. Mucositis following PFL was the dose-limiting toxicity. Local therapy included surgery in 15 patients and FHX chemoradiotherapy in 19 patients. The administration of FHX in this setting proved feasible and the regimen was given near the intended dose intensity in the majority of patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

The impact on survival by adjuvant chemotherapy and radiation therapy in stage II non-small-cell lung cancer.

Forty-nine consecutive patients with pathologic Stage II non-small-cell lung cancer treated over a 15-year period were retrospectively reviewed. The treatment strategy evolved during the period of review. Early patients were treated with surgery alone (S); subsequent patients were treated with adjuvant radiation therapy (SR); and more recent patients were treated with postoperative chemotherapy and radiation therapy (SRC). Fifteen patients received S alone, 10 patients received SR, and 24 patients received SRC. The median survival time (MST) of all 49 patients was 20 months, and the estimated 5-year survival was 25%. The MST of patients in each of the three treatment arms was S-6 months; SR-19 months; and SRC-25 months. The majority of patients died from systemic relapses or second primary lung cancers. The addition of adjuvant therapy (SR, SRC) significantly improved the MST of patients compared to surgery alone (S). The overall survival of patients did not change between treatment arms.

Adult↗

PubMed1992

High-dose consolidation therapy with autologous stem-cell rescue in stage IV breast cancer: follow-up report.

PURPOSE: Fifty-nine patients with newly diagnosed metastatic breast cancer were treated with induction chemotherapy followed by high-dose intensification and autologous stem-cell rescue (ASCR) to determine therapeutic efficacy. PATIENTS AND METHODS: Induction consisted of cyclophosphamide, doxorubicin, vincristine, and methotrexate with leucovorin rescue (LOMAC) in 27 patients, or fluorouracil, cisplatin, doxorubicin, and cyclophosphamide (FCAP) in 32 patients. Intensification after LOMAC was cyclophosphamide and thiotepa (CyTepa) with ASCR, and after FCAP it was cyclophosphamide, thiotepa, and carmustine (BCNU) in all but eight patients who received CyTepa. RESULTS: Median survival from study entry for the entire group was 13.3 months. Median time to progression from reinfusion for the 45 patients who underwent intensification was 7.5 months. After LOMAC and intensification, there were 12 complete responses (CR) (nine partial responses [PRs] after induction converted to CRs). Responses after FCAP and intensification were eight CRs (two PRs after induction converted to CRs). Median time to treatment failure from reinfusion was 5.4 months for LOMAC and intensification, and was 10.5 months for FCAP and intensification. Median survival from study entry was 15.1 months for all 27 LOMAC patients and 9.3 months for all 32 FCAP patients. Median time to treatment failure from reinfusion for 11 patients who were CRs at intensification has not been reached and is more than 13 months compared with a median of 5.5 months for the 23 patients in partial remission at intensification. CONCLUSIONS: High-dose intensification therapy has led to increased CR rates in metastatic breast cancer. The role of such therapy in the treatment of stage IV breast cancer requires further refinement.

Adult↗

PubMed1992

The treatment of hairy cell leukemia: an update.

The treatment of hairy cell leukemia (HCL) requires continuing update. The role for splenectomy is extremely limited. Alfa-interferon therapy has been available and utilized for five years; there have been few complete remissions. The experience with Pentostatin has resulted in a majority of clinical complete remissions after several months of therapy, but persistence of a small percentage of hairy cells in the bone marrow. The most recent therapeutic agent, 2-chloro-deoxyadenosine (2-CDA) is given for seven days and results in a complete remission in the great majority of patients with no evidence of persistent bone marrow disease. If this trend persists, 2-CDA will become first line therapy for HCL as it may cure the disease.

2-Chloroadenosine↗

PubMed1992

Interferon treatment for hairy cell leukemia: an update on a cohort of 69 patients treated from 1983-1986.

This report documents the follow-up information on 69 hairy cell leukemia (HCL) patients treated with interferon alpha-2b (IFN) as primary treatment from 1983-86. Follow-up through October 1991 shows only 11 patients have died. Forty-one of the 57 patients completing the intended 12 or more months of initial IFN treatment were eventually considered IFN failures. Thirty-nine required retreatment (38 received a second course of IFN and one received pentostatin). Two patients died without further therapy for HCL. The median time to interferon failure was 33 months. Sixteen patients are alive and have not required further treatment after completing their initial 12 or more months of interferon. Eight patients underwent a third course of interferon therapy at a median time after completion of a second course of IFN of 1.3 years. Seven patients developed a second malignancy; three of these patients developed a high-grade lymphoma between 3.5 and 6.5 years after initiation of interferon therapy. We conclude that although interferon provides excellent palliation, most patients will eventually require further treatment with interferon or chemotherapy. Future trials in HCL must be aware of second malignancies as a common cause of death.

Adult↗

PubMed1991

Modeling interpatient pharmacodynamic variability of etoposide.

This report describes approaches to modeling interpatient pharmacodynamic variability of etoposide effect as measured by white blood cell count nadir. Such models may be utilized in adaptive control dosing to individualize the dose administered to a patient with the aim of lessening the risk of severe myelosuppression. We have successfully employed adaptive control dosing of etoposide administered by 72-hour continuous infusion based on our prior pharmacodynamic model for white blood cell count nadir. Data from our most recent series of 41 patients were used to investigate new linear and nonlinear pharmacodynamic models. We then cross-validated our best models on data from an independent series of 27 similarly treated patients. We identified an unbiased model that exhibited high precision in both data sets (root mean square errors of 1.11 x 10(3) and 1.20 x 10(3) cells/microL, respectively). The optimal model was a nonlinear Hill model defined by 24-hour etoposide concentration, pretreatment white blood cell count, and pretreatment serum albumin level. The level of albumin was found to be both a component of kinetic (protein binding) and dynamic (patient health) variability. Patients with lower pretreatment albumin levels are at higher risk of severe myelosuppression during etoposide therapy.

Bias↗

PubMed1991

The proportion of abnormal karyotypes in acute leukemia samples related to method of preparation.

Bone marrow and peripheral blood were studied from 200 patients with acute leukemia [109 with acute myeloid leukemia (AML), 91 with acute lymphoblastic leukemia (ALL)] who had samples cultured for varying times and who had a mixture of chromosomally abnormal and normal cells. The mean percentage of abnormal metaphase cells increased with culture time. The peak was reached at 48 hours and declined slightly after 72 hours in culture for ALL patients. The mean percentage of abnormal cells increased up to 72 hours in culture for AML patients. In 68 patients (31 AML and 37 ALL), cytogenetic data were available from samples processed with both direct preparations and culture methods. The percentage of abnormal cells increased after culture in 49 patients (23 AML and 26 ALL), while it decreased or remained at the same level in 19 patients. For AML patients, the mean percentage of abnormal cells was significantly different between direct (38%) and cultured preparations (63%), (p less than 0.001). Seven of 9 patients with AML who showed a greater than 50% increase in abnormal cells after culture had either a t(8;21), t(15;17), or abnormalities involving 11q23. The two patients who showed a significant decrease in abnormal cells both had a translocation involving 11q13. Compared with ALL, more AML patients showed greater than 80% abnormal bone marrow metaphase cells at diagnosis or at relapse.

Acute Disease↗

PubMed1991

Paradoxical relationship between acetylator phenotype and amonafide toxicity.

Patients receiving the investigational antineoplastic agent amonafide underwent prospective determination of acetylator phenotype with use of caffeine as a test drug. Fast acetylators of caffeine had significantly greater toxicity (myelosuppression) after amonafide treatment than slow acetylators, presumably because of greater conversion of amonafide to the active acetylated metabolite. Furthermore, the estimated area under the plasma concentration-time curve of amonafide was significantly greater in the fast acetylators, indicating that the total plasma clearance was paradoxically lower in this group. It is hypothesized that this paradox is attributable to competition for oxidation of amonafide by its acetylated metabolite (parallel pathway interaction). Pretreatment white blood count and patient age were also independent predictors of leukopenia. In addition, it was noted that the ratio of actual to ideal body weight was significantly higher in the fast acetylators. Studies are in progress to determine the optimal amonafide dose in both acetylator subgroups.

Acetylation↗

PubMed1991

Prognostic factors in advanced head and neck cancer patients undergoing multimodality therapy.

A retrospective analysis was performed to investigate potential prognostic factors for complete remission to neoadjuvant chemotherapy and overall survival in patients with previously untreated stage III and stage IV head and neck cancer. Eighty consecutive patients were treated in one of two studies investigating three or four courses of neoadjuvant chemotherapy. Before local therapy and surgery and/or radiotherapy, 29% attained a complete remission. No strong significant and independent predictor of complete remission was identified. Only nodal stage (N) was found moderately associated with complete remission (p = 0.06). Node-negative patients had higher remission rates. Less important predictors were tumor stage (T) and site of disease; nasopharyngeal patients had superior remission rates (56%). With a median followup of 45 months and estimated 3-year survival rate of 38% (median 23.7 months), individual factors predictive of survival included pretherapy weight loss, performance status, alcohol use, pretherapy serum albumin level, site of disease, and N stage. In multivariate testing weight loss was identified as the strongest independent predictor of survival (p less than 0.0001) and surpassed other health status measures, such as performance status and serum albumin level. In addition, N stage (p = 0.019) and alcohol use (p = 0.017) were found to be predictive. A cross-classification by N stage and weight loss revealed risk groups with distinctly different prognoses, which may be useful for design and analysis in future trials.

Adolescent↗

PubMed1991

The effects of postinduction intensification treatment with cytarabine and daunorubicin in adult acute lymphocytic leukemia: a prospective randomized clinical trial by Cancer and Leukemia Group B.

Cancer and Leukemia Group B undertook a randomized trial of intensification treatment in adults aged 15 to 79 years with acute lymphocytic leukemia (ALL) in complete remission (CR). Daunorubicin (DNR), prednisone, vincristine (VCR), intrathecal (IT) methotrexate (MTX), and asparaginase produced 177 CRs in 277 patients. One hundred fifty-one patients were randomly assigned to receive treatment as follows: 74 received intensive cytarabine and DNR, and 77 received cycles of mercaptopurine (6-MP) and MTX, followed by 6MP, MTX, VCR, and prednisone for 3 years in all. One hundred twelve patients received CNS prophylaxis. Intensification produced major myelosuppression but did not improve remission duration (median, 21 months). Of the 151 patients with CRs who entered the intensification phase, 29% remain in continuous CR (43 to 117 months); in 19 patients, CRs have lasted for longer than 7 years. No relapses occurred after 60 months. Median survival from the time of randomization was 30 months. Those under 30 years of age responded more frequently, with longer CR and survival. While 53% of those aged 15 to 19 years remain in continuous CR, 92% of patients over 59 years have relapsed. The presence of a myeloid antigen on the leukemic cells was adversely prognostic for CR achievement and for survival. Pretreatment WBC and platelet levels independently affected CR duration and survival. Early M1 marrow development presaged longer remissions. CNS relapse occurred in 47 of 256 patients with normal CSF before treatment, in 29 before CNS prophylaxis. CNS disease occurred after CNS prophylaxis in 18 patients: 13 of 61 who had received standard premaintenance and five of 51 who received intensification. No advantage in CR duration or survival resulted from intensive treatment with DNR and cytarabine following induction of CR.

Adolescent↗

PubMed1991

Treatment of chemotherapy-induced anemia with recombinant human erythropoietin in cancer patients.

Thirty patients with chemotherapy-induced anemia were treated with recombinant human erythropoietin for 4 weeks. In this dose-escalation study, cohorts of five to eight patients were treated per dose level. The doses of erythropoietin were 25, 50, 100, 200, or 300 IU/kg/d given intravenously for 5 days each week. Of 30 patients, 15 (50%) had a greater than 10% increase of their hemoglobin (Hb) values and were considered responders. At the two highest dose levels, 11 of 13 patients (85%) responded. In the 15 responding patients, the mean Hb level increased by 1.7 g/dL from baseline compared with an average decrease of 1.5 g/dL in the previous cycles of chemotherapy without erythropoietin administration. Recombinant human erythropoietin is effective in ameliorating chemotherapy-induced anemia when administered in adequate doses.

Adult↗