Induction Therapy For Acute Leukemia Research Articles

How Long does it Take to Get a “Do not Resuscitate” Order?

Less than 50% of physicians know the resuscitation wishes of their patients and only a small fraction of patients have completed "do not resuscitate" (DNR) orders before death. One of the common reasons given by physicians is that the process of "getting a DNR" takes too long, and some authorities have suggested that additional reimbursement is needed. The purpose of this study is to assess how long the DNR education and consent process actually takes in practice. Our study group was a convenience sample of consecutive patients seen by experienced oncologists in a community and academic practice setting. Physicians were asked to record the time spent in DNR discussions with patients, the outcomes, and their comments. DNR orders were obtained on 16 of 22 patients with a single interview lasting a mean time of 16 minutes. Additional DNR orders were obtained on two more patients after a second interview of 6 patients, mean time 17.5 minutes. After a third interview of 4 patients, mean time 23 minutes, only 2 of 22 patients would not allow DNR orders. Of these two, one died intubated in the intensive care unit and the other underwent continued unsuccessful induction therapy for acute leukemia before dying. DNR orders can be obtained on nearly all patients within the time frame of an inpatient or outpatient visit. Time is not the main obstacle to DNR discussions, and additional reimbursement for additional time is not necessary. A small subset of patients continue to refuse DNR orders. Physician and patient reluctance to broach the subject may be a bigger impediment than time.

Adult acute leukemia

Untreated acute leukemia is a uniformly fatal disease with a median survival time shorter than 3 months. Current treatment strategies provide a significant increase in survival time for most patients, some of whom may be cured. The majority of patients with acute leukemia, however, ultimately die of the disease or complications of treatment. The effective treatment of acute leukemia requires (1) differentiation of acute myeloid leukemia (AML) from acute lymphoblastic leukemia (ALL) and recognition of clinically relevant subtypes; (2) identification of patients who are more likely or less likely than average to benefit from a conventional treatment; and (3) selection of therapy that provides a reasonable likelihood of response with acceptable risk of toxic effects. The diagnosis of acute leukemia is established in most cases by a bone marrow aspirate that demonstrates at least 30% blast cells. The traditional criteria to distinguish between AML and ALL rely on morphology and cytochemical reactions. Immunologic analysis of antigen expression and analysis for numerical or structural chromosomal abnormalities of leukemia cells are routinely feasible. Karyotypic analysis is of prognostic importance and should be performed on all diagnostic specimens of bone marrow aspirate. Immunophenotypic analysis may be useful to confirm the disease classification in selected cases. The importance of the routine immunophenotypic characterization of acute leukemia, however, is controversial. The subtypes that must be recognized because of the need for specific treatment include (a) acute promyelocytic leukemia (APL), which is the M3 subtype of AML, and (b) the L3 subtype or mature B-cell ALL. Induction therapy for acute leukemia is treatment intended to achieve induction of complete remission (CR). Complete remission is defined as the absence of morphologic evidence of leukemia after recovery of the peripheral blood cell counts. Failure to achieve CR may be attributed to death during chemotherapy-induced bone marrow hypoplasia or to drug resistance manifested either as failure to achieve hypoplasia or as persistent leukemia after recovery from hypoplasia. Postremission therapy is treatment administered in CR to prevent or delay relapse of the leukemia. However, the majority of patients have disease relapse. Intensification of therapy is a treatment strategy designed to overcome resistance to chemotherapy. Recent clinical trials of intensified induction or postremission therapy suggest improved outcome. However, the toxic effects of dose intensification can be substantial, limiting any potential benefit of this approach. Identification of prognostic factors may allow one to estimate the likelihood of an outcome, to determine an optimal treatment strategy. It is well established that age at the time of diagnosis, leukemia cell karyotype, and whether the leukemia is de novo or secondary are factors that influence treatment decisions. Patients with favorable prognostic factors should probably receive conventional therapy. Patients with unfavorable prognostic factors have shown little benefit from conventional therapy. In addition, factors that indicate poor outcome with conventional therapy are also predictive of poor outcome with intensified therapy. Consequently, these patients should be considered for investigational therapeutic strategies. The bias may be to counsel them to accept the potential increased morbidity of such treatment before there is definite evidence of the possibility of improved outcome. Induction chemotherapy for younger patients with AML (less than 55 years of age) in general consists of one or more courses of cytarabine (ara-C) and an anthracycline or an anthracycline derivative. Randomized trials have failed to confirm that treatment with either etoposide or high-dose ara-C induces disease remission. Patients with secondary AML, high levels of CD34 antigen expression, or an unfavorable karyotype, however, may benefit from ind

Guidelines for Hospitalization for Chemotherapy

Administration of cancer chemotherapeutic agents has shifted from the hospital to outpatient settings, usually the oncologist's office. Hospitalization for chemotherapy is now limited to specific situations, reflecting the need for prolonged direct observation, prevention or treatment of anticipated or real side effects, the use of special facilities and the minimization of certain treatment risks which cannot be effectively dealt with in an outpatient setting. New financial guidelines also have a significant impact on the location of chemotherapy administration. Outpatient chemotherapy has the advantages of allowing safe, easy drug administration, respecting the patient's wish to avoid hospitalization and providing a familiar facility, which enhances the patient's physical comfort and psychological well-being. The oncologist has direct and immediate control of drug administration, assistance is immediately available if problems arise, care is less expensive than inpatient care and overnight stay can be avoided. It also facilitates monitoring and control of treatment costs and allows treatment to be administered at the patient's convenience. Specific circumstances which justify hospitalization for chemotherapy, as detailed in Table 1, include: higher dosage cisplatin, special procedure chemotherapy, induction therapy for acute leukemia, high-dosage chemotherapy with or without stem cell/bone marrow transplantation, severely emetogenic chemotherapy, ifosfamide therapy, combination radiation therapy plus chemotherapy programs, coexistent medical problems (comorbidities), complex chemotherapy programs, the initial dose of chemotherapy while hospitalized for diagnosis of cancer, a scheduled dose of chemotherapy occurring during hospitalization for an unrelated problem, special measures required to prevent significant side effects, high-dose methotrexate protocols, intraperitoneal chemotherapy, certain investigational treatment protocols, and if chemotherapy administration is mandatory despite comorbidities that would ordinarily delay or contraindicate chemotherapy.

Infection prevention in severely myelosuppressed patients: A comparison between ciprofloxacin and a regimen of selective antibiotic modulation of the intestinal flora

purpose: To study whether oral ciprofloxacin would be as effective in preventing bacterial infections in severely myelosuppressed patients as selective antibiotic modulation of the gut flora with neomycin/polymyxin B sulfate/nalidixic acid (NPN). patients and methods: One hundred and five patients undergoing allogeneic or autologous bone marrow transplant, or induction therapy for acute leukemia in 1988 and 1989 were studied. Patients were stratified according to the type of therapy, and randomized in a ratio of 2:1 to either oral ciprofloxacin 500 mg BID, or a combination of oral neomycin 250 mg QID, polymyxin-B 100 mg QID, and oral nalidixic acid 1,000 mg BID. Treatment began on admission and continued until the absolute granulocyte count was greater than 500/mm 3 for 3 consecutive days. results: The 96 evaluable patients were evenly distributed over the 3 treatment groups; 63 patients received ciprofloxacin and 33 received NPN. Fever developed in 92% of patients on ciprofloxacin and in 97% of patients on NPN ( P = 0.66), 6.6 ± 5.8 and 7.2 ± 5.3 days from the start of prophylaxis, respectively. Twenty=five patients on ciprofloxacin developed 29 microbiologically documented infections, fewer than the 26 infections in the 22 patients on NPN ( P = 0.02). Patients on ciprofloxacin had fewer bacteremias (33%) than did the NPN patients (55%) ( P = 0.05). Gram-negative bacteremias were very rare (2 cases; no Enterobacteriaceae), but streptococcal bacteremias were frequent in both arms (27 cases). Side effects were not significantly different, but compliance with ciprofloxacin was better. conclusions: Ciprofloxacin is at least as effective as the combination of neomycin/polymyxin/nalidixic acid in the prophylaxis of bacterial infections in myelosuppressed patients, and is better tolerated. Additional agents to prevent streptococcal infections are needed.

Oral acyclovir as prophylaxis for bacterial infections during induction therapy for acute leukaemia in adults

We prospectively tested the hypothesis that prevention of herpes simplex virus infection with acyclovir might also reduce the incidence of bacterial infections in adult patients with acute leukaemia. During the first induction therapy a double-blind, randomized and placebo-controlled study was undertaken. Fifty-two patients were treated with 200 mg acyclovir orally four times daily throughout the induction period, whereas 55 patients received placebo. The groups were comparable with regard to age, cytotoxic chemotherapy and duration of neutropenia. Bacteraemias were significantly fewer in the acyclovir group (20 versus 41 episodes; P = 0.007). The number of isolated microorganisms causing bacterial or fungal infections was also lower during acyclovir prophylaxis (52 isolates, versus 93 isolates; P = 0.02). There was no significant difference between the groups with regard to the number of clinically documented infections or fevers of unknown origin. Herpes simplex virus isolations occurred only in the placebo group (P = 0.001). Thus, oral acyclovir prophylaxis was associated with reductions of all microbiologically documented infections suggesting that prevention of herpes simplex virus reactivation in acute leukaemia patients may reduce the occurrence of other infections.

The pathogenesis and clinical significance of cytologically detectable oral Candida in acute leukemia.

Using serial examination and oral cytology, 50 adult patients undergoing induction therapy for acute leukemia were studied for oral colonization with candida species. Ninety percent of patients were found to be colonized with Candida, with most of these colonizations present by day 14. The 30 patients exhibiting colonization with pseudohyphae received ketoconazole 400 mg daily by mouth. Of 20 patients in this group treated for 5 or more days, Candida organisms were eradicated in nine. Sixteen patients from the above group with persistent colonization on ketoconazole were treated by independent clinical decision for sustained fever and neutropenia with Amphotericin B, but only one responded by elimination of colonization. Seven of the 15 patients who did not initially receive ketoconazole developed Candida dissemination in contrast to two of 30 who received ketoconazole initially (P = 0.003, Fisher's exact test). No patient who initially had or acquired a negative cytology developed oral or disseminated candidiasis. Clinical oral candidiasis occurred in three patients, all of whom were receiving amphotericin B. Approximately 90% of these patients have or develop oral colonization with Candida organisms as identified by oral cytology. Those with colonization, both with and without pseudohyphae present, are at risk for dissemination. Amphotericin B does not eliminate colonization remaining after treatment with 400 mg of ketoconazole daily. More effective diagnostic and therapeutic strategies are needed to identify and eliminate Candida organisms and to prevent disseminated candidiasis in this population of patients.

Non-cardiogenic pulmonary edema complicating intermediate and high-dose Ara C treatment for relapsed acute leukemia.

Infection, hemorrhage and adult respiratory distress syndrome (ARDS) are pulmonary complications occurring after remission induction therapy for acute leukemia. The aim of this study was to analyze the incidence of these causes by serial roentgenogram, clinical, microbiological and laboratory tests in 21 patients (pts) with relapsed acute leukemia (18 X myeloid, 3 X lymphoblastic), an AML-pt (acute myeloid leukemia) suffering from secondary leukemia, and three pts with primary refractory leukemia following treatment with intermediate (IM) and high-dose cytosine arabinoside (HD-Ara C), in combination with amsacrine (AMSA)(n = 19), etoposide (VP 16) (n = 5) or Mitoxantrone (n = 1). Eleven out of 25 pts developed pulmonary complications, one of them with massive hemoptysis and roentgenographic signs of pulmonary bleeding, one suffering from protracted shock after a tumor lysis syndrome, two pts showing symptoms of a cardiogenic pulmonary edema complicating severe Candida pneumonia in one case and legionnaires' disease in the other. Seven of the eleven pts had a non-cardiogenic pulmonary edema with respiratory failure 1-14 days after cessation of induction or consolidation therapy. In six of the seven, there were no signs of cardiogenic, infectious or metabolic reasons, including fluid overload, for the pulmonary edema, one had as a contributing factor a Candida infection of the lung. Three of the seven patients recovered, four died (two following IM and two after HD-Ara C). Other adverse side effects, clearly attributable to HD-Ara C, included delirious state (n = 3), generalized erythema (n = 3), acute pancreatitis (n = 2), acute abdomen (n = 1) and conjunctivitis in almost all patients.(ABSTRACT TRUNCATED AT 250 WORDS)

The prognostic significance of myelonecrosis after induction therapy in acute leukemia.

Myelonecrosis is a rare antemortem finding in acute leukemia and its clinical significance is uncertain. The clinical events in nine patients with acute leukemia whose bone marrow biopsies after induction therapy revealed myelonecrosis were reviewed. No patient gained a complete remission and four patients achieved a partial remission. The median duration of survival was 2 months (range, less than 1 month to 8.5 months) from the start of therapy. Myelonerosis after induction therapy in acute leukemia indicates a very poor prognosis.

Urolithiasis in Childhood Acute Leukemia and Nonhodgkin’s Lymphoma

Ureteral calculi were found in 5 children who were receiving or had recently completed remission induction therapy for acute leukemia or lymphoma. All 5 patients had abdominal or back pain and 3 had gross hematuria. The diagnosis of urolithiasis was suggested by excretory urograms that showed obstructive uropathy (4 patients) and by computerized tomography scans that demonstrated ureterovesical obstruction (1 patient with acute renal failure and anuria). With a single exception the calculi were not associated with urinary tract infections. Chemical analyses in the 2 patients tested indicated that the stones were composed of calcium, in contrast to the uric acid and xanthine compositions of stones in earlier studies of patients with leukemia or lymphoma. Factors that might have predisposed our patients to calculi formation include corticosteroid therapy, immobilization owing to bed rest and urinary alkalization. Other possible contributing factors were urinary stasis (2 patients) and a familial tendency for renal calculi to develop (2). There was no evidence of idiopathic hypercalciuria in either patient tested. Prompt detection of urolithiasis in children undergoing induction chemotherapy for a malignant disease may avoid potentially serious consequences from urinary tract obstruction.

Autoimmune thrombocytopenia and neutropenia after remission induction therapy for acute leukaemia.

Patients with acute leukaemia who are exposed to intensive chemotherapy, with or without radiotherapy, may remain thrombocytopenic or neutropenic in remission. The incidence of these prolonged cytopenias was examined retrospectively in 46 patients in remission and prospectively in 14 patients. The patients were tested for the presence of autoantibodies to platelets and neutrophils using a fluorescent antihuman globulin technique with paraformaldehyde-fixed cells. In the retrospective study nine patients (20%) had neutrophil autoantibodies and seven (15%) had platelet autoantibodies; only one of the former had neutropenia and one of the latter thrombocytopenia. In the prospective study three (21%) had neutrophil autoantibodies and seven (50%) had platelet autoantibodies. One of the patients with platelet autoantibodies had transient thrombocytopenia, and shortened platelet survival was demonstrated. None of the patients with neutrophil autoantibodies had neutropenia. The rare occurrence of cytopenias in association with these autoantibodies was possibly due to bone marrow compensation for antibody-mediated cell destruction, although other possible mechanisms are discussed.

Daily evaluation of circulating granulocyte-monocyte progenitors during bone marrow recovery from induction therapy in acute leukemia

The notable increase of the circulating granulocyte-monocyte progenitors (PB CFU-GM) during bone marrow recovery following chemotherapy is a well known phenomenon. It has led to consider harvesting a large number of autologous stem cells by cytapheresis. Daily assessments have been conducted on the PB CFU-GM level in 9 patients with acute leukemia at the time of bone marrow regeneration after the first induction course in order to identify the circumstances of this rise. The PB CFU-GM maximum peak, of an average of 2142/ml, occurs between day 17 and day 23 after the chemotherapy has ended. A ten-fold increase of the PB CFU-GM level above normal values is maintained between 2 and 10 days. The PB CFU-GM peak coincides with that of the circulating immature myeloid cells and monocytes. The platelet rise above 100 × 10 9/1 always occurs 2–7 days before the PB CFU-GM peak.

The efficiency of strict reverse isolation and antimicrobial decontamination in remission induction therapy of acute leukemia.

The efficiency of strict reverse isolation and antimicrobial decontamination in remission induction therapy of acute leukemia was studied retrospectively in 47 patients who were treated with a standardized aggressive chemotherapy of daunorubicin and cytosine arabinoside. Twenty-two patients were treated in strict reverse isolation with antimicrobial decontamination and 25 patients in the open ward without any measures against infections. In the patients in isolation the incidence of new infections per patient was 0.77 compared to 1.42 in the control group. The rate of complete remissions was 77% in the patients in isolation vs. 56% in the control patients.

Prevention and treatment of infections at the time of induction therapy of acute leukemia with massive dose of oxacillin-ampicillin

Prevention and treatment of infections at the time of induction therapy of acute leukemia with massive dose of oxacillin-ampicillin