vitamin-b-12 and Neutropenia

Topics: Anemia, Megaloblastic; Diagnosis, Differential; Humans; Immune System Diseases; Metabolism, Inborn Errors; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Neutropenia; Prognosis; Vitamin B 12

Topics: Bone Marrow Cells; Cell Survival; Humans; Kinetics; Leukemia; Leukocyte Count; Mitosis; Muramidase; Neutropenia; Neutrophils; Vitamin B 12

Effective inhibition of cell division by anesthetics occurs only when cells are exposed to concentrations more than twice those required for anesthesia. Neutropenia following prolonged inhalation of nitrous oxide seems to be caused by a different mechanism, in which the cobalt in B12 is oxidised to the trivalent form by chemical reaction with nitrous oxide. B12 is thereby inactivated and this interferes with folate metabolism and thymidine synthesis: the effect may be detected after only a few hours in vivo exposure of mammals to 50% nitrous oxide. Unlike lymphocytes, the random motility of human neutrophils is not decreased by in vitro exposure to concentrations of halothane required for anesthesia. Similarly there is no effect on chemotaxis to casein and phagocytosis with exposure up to 2% halothane.

Topics: Anemia, Megaloblastic; Anesthetics; Animals; Bone Marrow; Cell Movement; Chemotaxis, Leukocyte; Halothane; Humans; Liver; Methionine; Neutropenia; Neutrophils; Nitrous Oxide; Phagocytosis; Rats; Spinal Cord; Thymidine; Vitamin B 12

Prior supplementation with folic acid and vitamin B12 is required to reduce pemetrexed therapy toxicity; the recommended lead-in time is at least 7 days. On the basis of previous pharmacokinetic and clinical studies, we hypothesized that the lead-in time could be shortened to 24 hours, enabling earlier commencement of standard chemotherapy; thus, we planned the first prospective trial of this regimen.. Patients with advanced nonsquamous non-small cell lung cancer who had not previously received cytotoxic chemotherapy were enrolled. After measurement of homocysteine concentrations, the patients received 1,000 μg of vitamin B12 by intramuscular injection and began taking 350-500 μg of oral folic acid daily. Starting 24-48 hours after the vitamin B12 injection, the patients received intravenous 500 mg/m(2) pemetrexed and 75 mg/m(2) cisplatin for 4 cycles at 3 weekly intervals. The primary endpoint was the proportion of patients who developed neutropenia grade ≥3.. Thirty patients received chemotherapy starting within 48 hours of the vitamin B12 injection. No treatment-related deaths or grade 4 toxicity occurred. Neutropenia grade ≥3, other laboratory toxicities grade ≥3, and nonlaboratory toxicities grade ≥3 occurred in 6.7%, 13%, and 13% of patients, respectively. The baseline homocysteine concentrations were not higher in patients with grade ≥3 toxicities than in the remainder of the cohort (mean values, 8.6 and 10.7 μmol/L, respectively). The response rate to chemotherapy was 43%.. The shortened vitamin supplementation was well tolerated and retained antitumor efficacy. Analysis of baseline homocysteine concentrations confirmed the efficacy of short-term vitamin supplementation.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Folic Acid; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Pemetrexed; Prospective Studies; Treatment Outcome; Vitamin B 12

Pemetrexed is a multitargeted folate pathway inhibitor with documented activity in non-small cell lung cancer (NSCLC). The presumed maximum tolerated dose is 500 mg/m2 every 3 weeks, but pemetrexed-related toxicity is ameliorated when folate and B12 supplementation is provided and therefore a higher dose intensity may be tolerated. The current exploratory study assessed the feasibility of administration of pemetrexed at a fixed dose of 1000 mg every 2 weeks in patients with relapsed or refractory NSCLC.. The first cohort of 12 patients received pemetrexed monotherapy. No dose-limiting grade 4 toxicity was noted after 4 cycles, so the subsequent cohort of 14 patients received additional anticancer agents (bevacizumab, erlotinib, carboplatin, docetaxel, vinorelbine) given along with dose-dense pemetrexed.. Toxicity overall was reversible and manageable. Among 19 patients who received pemetrexed either alone or with non-myelosuppressive targeted agents, there were only 2 instances of grade 4 neutropenia after prolonged treatment. Grade 3-4 hematologic toxicity was eventually noted in 11 of the 26 patients (42%; 95% confidence interval, 23% to 61%) after a median of 4 cycles (range, 2-14 cycles). There was no significant additional toxicity nor any treatment-related deaths.. Our preliminary observations indicate that dose-dense pemetrexed every 2 weeks is feasible and this regimen can be used as monotherapy. These data may serve as a scaffold for combination studies.

Topics: Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Dose-Response Relationship, Drug; Drug Combinations; Feasibility Studies; Female; Folic Acid Antagonists; Glutamates; Guanine; Hematologic Diseases; Humans; Male; Neutropenia; Pemetrexed; Vitamin B 12

This phase I study was conducted to determine the toxicities, pharmacokinetics, and recommended doses of pemetrexed in cancer patients with normal and impaired renal function.. Patients received a 10-minute infusion of 150 to 600 mg/m2 of pemetrexed every 3 weeks. Patients were stratified for independent dose escalation by measured glomerular filtration rate (GFR) into four cohorts ranging from > or = 80 to less than 20 mL/min. Pemetrexed plasma and urine pharmacokinetics were evaluated for the first cycle. Patients enrolled after December 1999 were supplemented with oral folic acid and intramuscular vitamin B12.. Forty-seven patients were treated with 167 cycles of pemetrexed. Hematologic dose-limiting toxicities occurred in vitamin-supplemented patients (two; 15%) and non-supplemented patients (six; 18%), and included febrile neutropenia (four patients) and grade 4 thrombocytopenia (two patients). Nonhematologic toxicities included fatigue, diarrhea, and nausea, and did not correlate with renal function. Accrual was discontinued in patients with GFR less than 30 mL/min after one patient with a GFR of 19 mL/min died as a result of treatment-related toxicities. Pemetrexed plasma clearance positively correlated with GFR (r2 = 0.736), resulting in increased drug exposures in patients with impaired renal function. With vitamin supplementation, pemetrexed 600 mg/m2 was tolerated by patients with a GFR > or = 80 mL/min, whereas patients with a GFR of 40 to 79 mL/min tolerated a dose of 500 mg/m2.. Pemetrexed was well tolerated at doses of 500 mg/m2 with vitamin supplementation in patients with GFR > or = 40 mL/min. Additional studies are needed to define appropriate dosing for renally impaired patients receiving higher dose pemetrexed with vitamin supplementation.

Topics: Adult; Aged; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Diarrhea; Drug Administration Schedule; Fatigue; Female; Folic Acid; Glutamates; Guanine; Humans; Kidney Failure, Chronic; Male; Middle Aged; Nausea; Neoplasms; Neutropenia; Pemetrexed; Thrombocytopenia; Vitamin B 12

The purpose of this study was to determine the maximum tolerated dose (MTD) and recommended dose (RD) of pemetrexed with folate and vitamin B12 supplementation (FA/VB(12)) in Japanese patients with solid tumours and to investigate the safety, efficacy, and pharmacokinetics of pemetrexed. Eligible patients had incurable solid tumours by standard treatments, a performance status 0-2, and adequate organ function. Pemetrexed from 300 to 1,200 mg m(-2) was administered as a 10-min infusion on day 1 of a 21-day cycle with FA/VB(12). Totally, 31 patients were treated. Dose-limiting toxicities were alanine aminotransferase (ALT) elevation at 700 mg m(-2), and infection and skin rash at 1,200 mg m(-2). The MTD/RD were determined to be 1,200/1,000 mg m(-2), respectively. The most common grade 3/4 toxicities were neutropenia (grade (G) 3:29, G4:3%), leucopenia (G3:13, G4:3%), lympopenia (G3:13%) and ALT elevation (G3:13%). Pemetrexed pharmacokinetics in Japanese were not overtly different from those in western patients. Partial response was achieved for 5/23 evaluable patients (four with non-small cell lung cancer (NSCLC) and one with thymoma). The MTD/RD of pemetrexed were determined to be 1,200/1,000 mg m(-2), respectively, that is, a higher RD than without FA/VB(12) (500 mg m(-2)). Pemetrexed with FA/VB(12) showed a tolerable toxicity profile and potent antitumour activity against NSCLC in this study.

Topics: Adult; Aged; Alanine Transaminase; Antineoplastic Agents; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Folic Acid; Glutamates; Guanine; Humans; Infusions, Intravenous; Japan; Male; Maximum Tolerated Dose; Middle Aged; Neoplasms; Neutropenia; Pemetrexed; Safety; Treatment Outcome; Vitamin B 12

A prospective, randomized study was conducted to evaluate the role of vitamin B12 and folinic acid supplementation in preventing zidovudine (ZDV)-induced bone marrow suppression. Seventy-five human immunodeficiency virus (HIV)-infected patients with CD4+ cell counts < 500/mm3 were randomized to receive either ZDV (500 mg daily) alone (group I, n = 38) or in combination with folinic acid (15 mg daily) and intramascular vitamin B12 (1000 micrograms monthly) (group II, n = 37). Finally, 15 patients were excluded from the study (noncompliance 14, death 1); thus, 60 patients (31 in group I and 29 in group II) were eligible for analysis. No significant differences between groups were found at enrollment. During the study, vitamin B12 and folate levels were significantly higher in group II patients; however, no differences in hemoglobin, hematocrit, mean corpuscular volume, and white-cell, neutrophil and platelet counts were observed between groups at 3, 6, 9 and 12 months. Severe hematologic toxicity (neutrophil count < 1000/mm3 and/or hemoglobin < 8 g/dl) occurred in 4 patients assigned to group I and 7 assigned to group II. There was no correlation between vitamin B12 or folate levels and development of myelosuppression. Vitamin B12 and folinic acid supplementation of ZDV therapy does not seem useful in preventing or reducing ZDV-induced myelotoxicity in the overall treated population, although a beneficial effect in certain subgroups of patients cannot be excluded.

Topics: Adult; Anemia; Bone Marrow Diseases; CD4 Lymphocyte Count; Female; Folic Acid; Hematologic Diseases; HIV Infections; Humans; Leucovorin; Male; Neutropenia; Prospective Studies; Vitamin B 12; Zidovudine

We conducted a double-blind, placebo-controlled trial of oral azidothymidine (AZT) in 282 patients with the acquired immunodeficiency syndrome (AIDS) or AIDS-related complex. Although significant clinical benefit was documented (N Engl J Med 1987; 317:185-91), serious adverse reactions, particularly bone marrow suppression, were observed. Nausea, myalgia, insomnia, and severe headaches were reported more frequently by recipients of AZT; macrocytosis developed within weeks in most of the AZT group. Anemia with hemoglobin levels below 7.5 g per deciliter developed in 24 percent of AZT recipients and 4 percent of placebo recipients (P less than 0.001). Twenty-one percent of AZT recipients and 4 percent of placebo recipients required multiple red-cell transfusions (P less than 0.001). Neutropenia (less than 500 cells per cubic millimeter) occurred in 16 percent of AZT recipients, as compared with 2 percent of placebo recipients (P less than 0.001). Subjects who entered the study with low CD4 lymphocyte counts, low serum vitamin B12 levels, anemia, or low neutrophil counts were more likely to have hematologic toxic effects. Concurrent use of acetaminophen was also associated with a higher frequency of hematologic toxicity. Although a subset of patients tolerated AZT for an extended period with few toxic effects, the drug should be administered with caution because of its toxicity and the limited experience with it to date.

Topics: Acquired Immunodeficiency Syndrome; Administration, Oral; AIDS-Related Complex; Anemia; Antiviral Agents; Blood Transfusion; Bone Marrow; Clinical Trials as Topic; Double-Blind Method; Erythrocyte Count; Female; Hemoglobins; Humans; Leukocyte Count; Male; Neutropenia; Platelet Count; Random Allocation; Thymidine; Vitamin B 12; Zidovudine

Administration of vitamin B12 and folic acid for 7 days prior to the administration of the first dose of pemetrexed is recommended. However, vitamin supplementation rarely is initiated less than 7 days prior to the first dose of pemetrexed. Therefore, we analyzed the safety of pemetrexed with vitamin supplementation for less than 7 days prior to the first dose of pemetrexed.. Patients were classified into 2 groups according to the duration of vitamin supplementation prior to the first dose of pemetrexed: group A received vitamin supplementation for 7 days or more, and group B received vitamin supplementation for less than 7 days. We analyzed adverse effects, such as myelosuppression, rash, and diarrhea, after 1 cycle of pemetrexed therapy.. A total of 70 patients were administered pemetrexed; 40 patients were men and 30 were women with a median age of 64.5 years(range, 43-86 years). A total of 57 patients were classified into group A and 13 into group B; 33 patients were administered pemetrexed as a first-line treatment. Neutropenia of Grade 3 or more was observed in 4/49(8.2%)patients in group A and 2/13(15.4%)patients in group B(p=0.60). There were no significant differences in the rates of occurrence of neutropenia, rash, and diarrhea.. This retrospective study indicated that patients could be safely treated with pemetrexed if vitamin supplementation is initiated for less than 7 days prior to the first administration of pemetrexed. However, further studies are needed because of a lack of statistical power and adjustment for confounding factors.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Carcinoma, Non-Small-Cell Lung; Diarrhea; Dietary Supplements; Drug Combinations; Exanthema; Female; Folic Acid; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Middle Aged; Neutropenia; Pemetrexed; Retrospective Studies; Vitamin B 12

Topics: Anemia; Humans; Leukemia, Myeloid, Acute; Male; Neutropenia; Vitamin B 12; Vitamin B 12 Deficiency

Topics: Anemia; Anemia, Megaloblastic; Biomarkers, Tumor; Diagnosis, Differential; Erythroblasts; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Severity of Illness Index; Vitamin B 12; Vitamin B 12 Deficiency

A 50-year-old man presented with a four-year history of unsteadiness, with recent falls and tingling in his fingers. Neurological examination found an ataxic gait, with a positive Romberg's sign. There was distal wasting and weakness in all four limbs and impaired co-ordination, with pseudoathetosis in the arms. Initial investigations showed a normochromic, normocytic anaemia, leucopenia, neutropenia and a low vitamin B(12) (172 ng/L). Treatment with intramuscular cobalamin injections showed no clinical improvement. Further investigations showed an undetectable caeruloplasmin (<0.085 g/L), a very low serum copper (1.1 μmol/L) and a markedly raised serum zinc concentration (36.2 μmol/L). On detailed questioning it became apparent that he had ill-fitting dentures requiring excessive use of denture fixative with high zinc content. The patient was switched to a non-zinc containing denture fixative and commenced copper supplementation. Although within three months the bone marrow suppression had resolved, there was no clinical improvement in neurological presentation. Questioning a patient about their denture fixative usage and checking if zinc is an ingredient may be considered during an investigation for myelopolyneuropathy when vitamin B(12) deficiency is not a cause.

Topics: Anemia; Ceruloplasmin; Copper; Dental Cements; Dentures; Diagnosis, Differential; Heavy Metal Poisoning; Humans; Male; Middle Aged; Neutropenia; Poisoning; Polyneuropathies; Vitamin B 12; Vitamin B 12 Deficiency; Zinc

The objectives of the analysis were to characterize the time course of neutropenia after pemetrexed administration using an established semimechanistic-physiologic model, characterize the relationship between pemetrexed exposure and neutropenia, and describe differences in neutropenic response by vitamin supplementation status and between Japanese and Western patients.. An eight-compartment population pharmacokinetic/pharmacodynamic model was used to describe the absolute neutrophil count (ANC)-time profile (neutropenic response) following pemetrexed doses of 300 to 1,400 mg/m(2) administered every 21 days. The analyses pooled data from 13 studies including 279 patients (161 supplemented with oral folic acid and intramuscular vitamin B(12), and 118 unsupplemented; 248 Western and 31 Japanese) who received 857 treatment cycles.. Vitamin supplementation status, ethnic origin, and drug exposure were the dominant predictors of neutropenic response. Vitamin supplementation diminishes neutropenic response to pemetrexed. Model-predicted ANC nadirs for the "typical" Western patient receiving 500 mg/m(2) pemetrexed +/- vitamin supplementation were 2.74 x 10(9)/L and 1.70 x 10(9)/L, respectively. Japanese patients had a less pronounced neutropenic response to pemetrexed relative to Western patients. The model-predicted ANC nadir for Japanese patients receiving 500 mg/m(2) pemetrexed with vitamin supplementation was 2.66 x 10(9)/L. Values for the 1,000 mg/m(2) dose with vitamin supplementation were 1.91 x 10(9)/L and 1.34 x 10(9)/L for Japanese and Western patients, respectively. Increased albumin, decreased cystathionine, and decreased body surface area were also associated with increased neutropenic response.. The neutropenic response to higher pemetrexed doses administered with vitamin supplementation is tolerable. All other factors equal, Japanese patients have a lesser neutropenic response to pemetrexed relative to Western patients.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Asian People; Dietary Supplements; Female; Folic Acid; Glutamates; Guanine; Humans; Male; Middle Aged; Neutropenia; Pemetrexed; Time Factors; Vitamin B 12; White People

Bronchioloalveolar carcinoma (BAC) and adenocarcinoma mixed subtype with bronchioloalveolar features (ADC-WBF) represent a unique anatomo-clinical entity accounting for some 20% of non-small cell lung cancers (NSCLC). These tumors seem less sensitive to chemotherapy than other NSCLC. We report two cases of advanced ADC-WBF treated with second-line and fourth-line pemetrexed. Major and durable radiological response associated with clinical and functional improvement was achieved in both patients, without important drug toxicity. After treatment arrest, the two patients experienced progressive disease but responded to retreatment with pemetrexed. Recent data suggest that paclitaxel-based chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitors could be an acceptable therapeutic strategy in unresectable CBA and ADC-WBF. The cases reported here and preclinical findings suggest a therapeutic efficacy of pemetrexed in these tumors. Prospective studies are required to evaluate this hypothesis.

Topics: Adenocarcinoma; Adenocarcinoma, Bronchiolo-Alveolar; Aged; Antimetabolites, Antineoplastic; Bone Neoplasms; Cough; Disease Progression; Dyspnea; Folic Acid; Glutamates; Guanine; Humans; Lung Neoplasms; Male; Neoplasm Staging; Neutropenia; Pemetrexed; Remission Induction; Renal Insufficiency; Smoking; Tomography, X-Ray Computed; Vitamin B 12

The objectives of these analyses were to (1) develop a semimechanistic-physiologic population pharmacokinetic/pharmacodynamic (PK/PD) model to describe neutropenic response to pemetrexed and to (2) identify influential covariates with respect to pharmacodynamic response.. Data from 279 patients who received 1,136 treatment cycles without folic acid or vitamin B12 supplementation during participation in one of eight phase II cancer trials were available for analysis. Starting doses were 500 or 600 mg pemetrexed per m2 body surface area (BSA), administered as 10-min intravenous infusions every 21 days (1 cycle). The primary analyses included 105 patients (279 cycles) for which selected covariates-including vitamin deficiency marker data (i.e., homocysteine, cystathionine, methylmalonic acid, and methylcitrate [I, II, and total] plasma concentrations)-were available. Classical statistical multivariate regression analyses and a semimechanistic-physiologic population PK/PD model were used to evaluate neutropenic response to single-agent pemetrexed administration.. The timecourse of neutropenia following single-agent pemetrexed administration was adequately described by a semimechanistic-physiologic model. Population estimates for system-based model parameters (i.e., baseline neutrophil count, mean transit time, and the feedback parameter), which mathematically represent current understanding of the process and physiology of hematopoiesis, were consistent with previously reported values. The population PK/PD model included homocysteine, cystathionine, albumin, total protein, and BSA as covariates relative to neutropenic response.. These results support the programmatic decision to introduce folic acid and vitamin B12 supplementation during pemetrexed clinical development as a means of normalizing patient homocysteine levels, thereby managing the risk of severe neutropenia secondary to pemetrexed administration. The current results also suggest that the addition of vitamin B6 supplementation to normalize patient cystathionine levels may further decrease the incidence of grade 4 neutropenia following pemetrexed administration. The results also suggest the use of folic acid as a means of lessening hematologic toxicity following administration of cytotoxic agents other than antifolates.

Topics: Adult; Aged; Algorithms; Analysis of Variance; Antimetabolites, Antineoplastic; Area Under Curve; Avitaminosis; Blood Cell Count; Body Surface Area; Clinical Trials, Phase II as Topic; Data Interpretation, Statistical; Female; Folic Acid; Glutamates; Guanine; Humans; Infusions, Intravenous; Leukocyte Count; Male; Middle Aged; Models, Statistical; Neutropenia; Neutrophils; Pemetrexed; Population; Vitamin B 12; Vitamin B 6; Vitamins

Topics: Adolescent; Autoimmune Diseases; Child, Preschool; Erythema Multiforme; Humans; Neutropenia; Phenobarbital; Vitamin B 12

Topics: Anemia; Ceruloplasmin; Copper; Female; Follow-Up Studies; Hematologic Diseases; Humans; Magnetic Resonance Imaging; Metabolic Diseases; Middle Aged; Nervous System Diseases; Neural Conduction; Neutropenia; Peripheral Nerves; Spinal Cord; Vitamin B 12; Zinc

Although patients with malignant disease frequently use dietary supplements, the effects of these agents with regard to chemotherapy are unclear. Therefore, the authors investigated the influence of vitamin B12, folate, and nutritional supplements on chemotherapy-induced toxicity.. Women with breast carcinoma were asked to complete a questionnaire that recorded their use of dietary supplements. Blood samples were obtained for the assessment of serum vitamin B12 and folate levels before and after the first cycle of chemotherapy and for weekly complete blood counts. Toxicity was evaluated by measuring absolute neutrophil counts and the frequency and severity of oral mucositis.. Of the 49 women who submitted questionnaires, 35 (71%) took a combined total of 165 supplements. Compared with patients in a previous study (performed in 1990), patients in the current study had dramatically increased serum folate levels. Initial neutrophil count, but not type of chemotherapy, patient age, or serum vitamin B12 level, was predictive of nadir absolute neutropenia and the decrease from initial neutrophil count to nadir (Nfall). After adjusting for initial neutrophil count, Nfall was found to be lower for women who were taking supplements compared with women who were not taking supplements (P = 0.01) and for women who were taking multivitamins (P = 0.01) or vitamin E (P = 0.03). Women with serum folic acid levels < 20 ng/mL had a smaller decrease in neutrophil count after chemotherapy than did women with higher folate levels (P = 0.04). No significant association between oral mucositis and initial neutrophil count, nadir neutrophil count, Nfall, age, vitamin B12 level, or folate level was found.. The decrease in neutrophil count caused by chemotherapy was ameliorated by dietary supplementation with a multivitamin or vitamin E. In contrast, high serum folate levels were associated with the exacerbation of this decrease in neutrophil count.

Topics: Adult; Aged; Antineoplastic Agents; Antioxidants; Breast Neoplasms; Dietary Supplements; Female; Folic Acid; Humans; Leukocyte Count; Middle Aged; Mucous Membrane; Neutropenia; Neutrophils; Surveys and Questionnaires; Vitamin B 12

Topics: Acquired Immunodeficiency Syndrome; Agranulocytosis; Folic Acid; Humans; Lithium; Neutropenia; Vitamin B 12; Zidovudine

Serum unsaturated vitamin B12-binding capacity (UBBC) has been shown to fluctuate with neutrophil levels and has been reported to correlate with TBGP in normal and hyperleukocytic states. However, the present report demonstrates that the above relationship is not present in neutropenia, suggesting that some of our concepts regarding UBBC may have to be reexamined, since factors other than TBGP appear to be operative. There was a wide scatter of UBBC values among the 39 neutropenic subjects studied, the mean being significantly above normal. There were few low values. High UBBC was primarily confined to subjects with transient neutropenia. Normal values were generally seen in steady neutropenia. The difference in UBBC was primarily due to Transcobalamin I, the other serum binders being similar in both groups. No other significant diagnostic pattern of UBBC was found. Recovery from neutropenia was accompanied by a rise in UBBC in all cases except in four patients whose UBBC was initially very high and fell with recovery. No discernible pattern of serum B12 levels existed, although subnormal levels without evidence of B12 deficiency were found in three of the seven patients with aplastic anemia. Serum B12 levels did not change with recovery in approximately half of the neutropenic subjects, change being variable in the others. Neither serum B12, UBBC, total B12-binding capacity, or any of the three serum B12 binders correlated with neutrophil count, bone marrow findings, TBGP, or granulocyte turnover rate.

Topics: Agranulocytosis; Anemia, Aplastic; Bone Marrow Cells; Carrier Proteins; Granulocytes; Humans; Leukocyte Count; Neutropenia; Neutrophils; Transcobalamins; Vitamin B 12