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Time series for modelling counts from a relapsing-remitting disease: application to modelling disease activity in multiple sclerosis.

Many chronic diseases are relapsing-remitting diseases, in which subjects alternate between periods with increasing and decreasing disease activity; relapsing-remitting multiple sclerosis is an example. This paper proposes two classes of models for sequences of counts observed from a relapsing-remitting disease. In the first, the relapsing-remitting nature of the data is modelled by a Poisson time series with a periodic trend in the mean. In this approach, the mean is expressed as a function of a sinusoidal trend and past observations of the time series. An algorithm that uses GLIM is developed, and it results in maximum-likelihood estimation for the amplitude, frequency and autoregressive effects. In the second class of models, the relapsing-remitting behaviour is described by a Poisson time series in which changes in the mean follow a latent Markov chain. An EM algorithm is developed for maximum-likelihood estimation for this model. The two models are illustrated and compared with data from a study evaluating the use of serial magnetic resonance imaging as a measure of disease activity in relapsing-remitting multiple sclerosis.

Algorithms↗

Endometrial carcinoma--relative effectiveness of adjuvant irradiation vs therapy reserved for relapse.

Fifty-four patients with recurrent endometrial carcinoma were identified from a retrospective review of charts of 304 endometrial cancer patients seen between 1983 and 1989 at our center. A review was undertaken to identify the patterns of relapse, to determine the outcome of salvage treatment, to examine the factors predictive of effective salvage, and, if salvage is effective, to assess an alternative strategy to routine adjuvant postoperative pelvic radiotherapy. Forty percent of the entire recurrent population are long-term survivors. Of the 54 relapsing patients, primary therapy had been surgery alone in 32 and surgery and adjuvant radiotherapy (rt) in 22. Isolated pelvic recurrence was the predominate relapse site in those who had not received adjuvant pelvic RT as primary therapy (23 of 32 or 72%). Distant relapse predominated in those who received adjuvant RT (17 or 22 or 77%). Twenty-eight (54%) failed in the pelvis alone, and 26 (46%) had a component of distant failure. Of the 28 with isolated pelvic relapse, 16 had vaginal mucosal disease involvement only and 12 had disease in the parametrium and/or the pelvic sidewall. With a minimum follow-up for the survivors of 5 years, 21 of the 28 with isolated pelvic relapse received radical radiotherapy and 14 or 67% had maintained pelvic control until death or last follow-up. Eleven of 14 (79%) with disease confined to the mucosa had pelvic control, whereas only 3 of 7 (43%) with extramucosal disease were controlled. No patient experienced major treatment-related toxicity. Tumor size, anatomic extent of pelvic recurrence, RT dose, and disease-free interval were examined for prognostic significance for pelvic control and survival by univariate analysis. Only anatomic extent of pelvic recurrence showed a nonstatistically significant trend as a predictor for control with P = 0.08. In conclusion, a significant proportion of patients with disease recurrence confined to the pelvis can be rendered disease-free long-term with maintained pelvic control. A reexamination of the role of routine adjuvant pelvic RT is therefore undertaken in light of these data.

Aged↗

Detection of minimal residual disease in peripheral blood prior to clinical relapse of childhood acute lymphoblastic leukaemia using PCR.

Submicroscopic evidence of persistent minimal residual disease (MRD) in first remission bone marrow samples from children with acute lymphoblastic leukaemia (ALL) indicates a high risk of clinical relapse. Since microscopic evidence of leukaemic lymphoblasts is often present in the peripheral blood in the weeks before clinical presentation at diagnosis or relapse, peripheral blood may be used instead of bone marrow to detect MRD in ALL patients. We examined a median of 0.165 microg (from 1.0-2.0x10(4)cells) genomic DNA from archived peripheral blood smears collected 8-16 months prior to clinical relapse in eight children with ALL for evidence of MRD. We used the polymerase chain reaction and primers designed to identify clonal antigen receptor gene rearrangements. Among the seven patients with bone marrow relapse, MRD was detected at a median of 1.2 months (0-8 months) prior to clinical relapse, indicating that MRD in the peripheral blood may be a late event in the course of leukaemic relapse. A prospective MRD study in ALL patients analysing larger numbers of peripheral blood cells will be needed to evaluate the utility of peripheral blood over bone marrow for MRD testing in childhood ALL.

Child↗

Intermediate-dose Ara-C/m-AMSA for remission induction and high-dose Ara-C/m-AMSA for intensive consolidation in relapsed and refractory adult acute myelogeneous leukemia.

Thirty-four consecutive patients with either relapsed (n = 28) or primary refractory AML (n = 6) were treated with one or two cycles of intermediate-dose (ID) cytosine arabinoside (Ara-C) (1 g/m2 i.v. q 12 h days 1-6) and amsacrine (m-AMSA) (120 mg/m2 i.v. days 5-7). Patients reaching complete remission (CR) were consolidated with one cycle of Ara-C 3 g/m2 i.v. q 12 h days 1-4 and m-AMSA 120 mg/m2 i.v. day 5. The median duration of the preceding remission was 8 months and median time from last chemotherapy until relapse 3.1 months. Of the relapsed patients, 22/28 (79%) achieved CR regardless of the type of prior intensive maintenance (HD Ara-C/m-AMSA/5-azacytidine) (AZA) or daunorubicin (DNR/CD-Ara-C). Three of the 28 (11%) patients died during hypoplasia; 3/28 (11%) were refractory to 2x ID-Ara-C/m-AMSA. Three of the 28 patients died in CR during hypoplasia after intensive consolidation with HD-Ara-C. Predictive factors for remission were duration of preceding remission and the time from last chemotherapy to relapse. Three patients were transplanted in second CR. One of the six refractory patients reached CR, two remained refractory, and three died during hypoplasia. The median duration of disease-free survival (DFS) of relapsed patients was 3.3 months without further treatment; median survival of responding patients (20 relapsed patients, 1 refractory patient) was 4.5 months, overall survival (n = 29) was 4.8 months. Patients receiving BMT were censored at the time of BMT. Seven patients experienced lung toxicity due to Ara-C, four of whom died.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Ploidy changes between diagnosis and relapse in childhood renal tumours.

Ploidy patterns, analysed by flow cytometry (FCM) and image analysis (IA), were investigated at relapse in a group of six children with renal tumours [five Wilms' tumour (WT) and one bone metastasizing renal tumour of childhood (BMRTC)] and results compared with diagnostic profiles. IA detected one or more aneuploid populations in five of 12 tumours which were diploid on FCM. Patterns in three of six patients [two with unfavourable histology (UH) and one with favourable histology (FH)] were aneuploid at diagnosis and relapse, two patients (one FH, one BMRTC) developed aneuploid features at relapse and one patient with a tetraploid tumour was diploid at relapse. Histology patterns were similar at diagnosis and relapse in all patients. Three of six patients (two UH, one BMRTC) have died of disease. This report highlights (1) the superiority of IA over FCM in detecting aneuploid populations and (2) changes in ploidy status which have not previously been reported in these tumours. Overinterpretation of DNA status at relapse may prove misleading.

Aneuploidy↗

A depot neuroleptic withdrawal study. Plasma concentration of fluphenazine and flupenthixol and relapse frequency.

A double-blind withdrawal trial in 41 chronic schizophrenic outpatients was carried out during 6 months. Depot neuroleptics (fluphenazine decanoate or flupenthixol decanoate) were compared with placebo to evaluate clinical and neurological effects during continued therapy and during withdrawal. The drugs were significantly more effective than placebo in preventing relapse and rehospitalization. In the placebo group 62% relapsed compared to 27% in the drug group. There was a weak and nonsignificant tendency to a higher relapse frequency in the flupenthixol group compared to the fluphenazine group. After withdrawal for 6 months, plasma levels for fluphenazine were detectable. Plasma levels for flupenthixol were not detectable after 9 weeks of withdrawal. The differences in the plasma levels may possibly explain the difference in relapse rate between the two depot neuroleptics. Furthermore, it was found that the patients who relapsed during fluphenazine treatment had a significantly lower plasma level of the drug than patients who did not relapse during treatment. The results from this study provide some information on the therapeutic levels of fluphenazine and flupenthixol in schizophrenic patients.

Delayed-Action Preparations↗

Persistence of relapse of morphine-seeking behavior in rats: the relative role of certain biological variables.

The theory that narcotic-induced protracted biological changes are responsible for relapse of opiate-reinforced behavior was examined in the rat. Groups of rats were conditioned to prefer a distinctive environment by pairing it with morphine doses from 1-200 mg/kg, and were retested for persistence of this preference after a 3-week abstinence period. They were then observed for protracted signs such as sensitivity to naloxone, tolerance to morphine analgesia, hyperaggression, or changes in endocrine activity. Acquisition and relapse of the preference, as well as long-term tolerance, were dose related. None of the purported protracted signs showed any consistent relationship to the tendency to relapse. However, relapse correlated significantly with original acquisition scores in all relapsing groups. The results suggest that original conditioning factors, rather than protracted changes, are responsible for the observed relapse.

Aggression↗

Pathogenetic role of Helicobacter pylori in duodenal ulcer disease. Multivariate analysis of factors affecting relapse.

The pathogenesis of duodenal ulcer disease is multifactorial and the contribution of Helicobacter pylori in relation to the other factors to the release of duodenal ulcer is unknown. To investigate this, we studied 147 patients with endoscopically proven healed ulcers. These patients were randomized to receive either placebo, misoprostol 200 micrograms or misoprostol 300 micrograms four times daily, and clinical, personal, physiological and endoscopic characteristics were obtained prospectively. Endoscopy was performed at the active phase of the ulcer and when the ulcer healed. Biopsies were taken from the antrum to assess histologically for: (1) the activity of gastritis as assessed by the degree of polymorph infiltration, (2) the degree of chronic inflammation by the degree of chronic inflammatory cells infiltration and degree of mucosal degeneration, and (3) bacteriologically for the presence of H. pylori. The severity of the gastritis and the bacterial density were graded independently by two pathologists. The patients were assessed at two-month intervals for 12 months or until the ulcer relapsed. The results demonstrated that the relapse rates of duodenal ulcer were similar in the three treatment groups. The relapse rate was higher in the group with higher density of the bacteria (P less than 0.05). The degree of gastritis did not affect the relapse rate of duodenal ulcer in either the placebo or misoprostol group or in all patients combined. Stepwise logistic regression analysis identified that increased duodenal inflammation, male sex, early-onset disease, and H. pylori adversely affected relapse of the ulcer. We conclude that multiple factors affect the relapse of duodenal ulcer and H. pylori is one of them.

Adult↗

Refractory and relapsing Hodgkin's disease: role of high-dose chemotherapy with bone marrow transplantation.

Thirty percent of adult patients with Hodgkin's disease fail primary treatment or relapse after treatment. Whereas overall mortality for Hodgkin's disease is about 20%, half the patients who relapse will die. Among patients with refractory or relapsing disease, about a third can be rescued by conventional salvage treatment. Unfortunately, except for patients with late relapse, remission after conventional salvage treatment is generally not of long duration. However, durable complete remissions can now be achieved in nearly a third of patients with refractory or relapsing disease by means of very aggressive (myeloablative) chemotherapy with consecutive autologous bone marrow transplantation (aBMT). The rate of durable complete remissions seems to be even higher if previous exposure to chemotherapeutic agents is not in excess of two different treatment protocols (optimal timing of aBMT) and if responsiveness to cytotoxic drugs is preserved (low degree of drug resistance). Bone marrow transplantation should be restricted to patients whose resulting long-term prognosis justifies such radical treatment. Reflecting ongoing clinical therapy-studies, in particular in Germany, the role of bone marrow transplantation in a general concept of salvage treatment should be pointed out. Patients should be considered candidates if they fail alternating primary chemotherapy or develop an early relapse after this treatment, but still show responsiveness to chemotherapeutic agents.

Antineoplastic Combined Chemotherapy Protocols↗

Risk of relapse in new cases of ulcerative colitis and indeterminate colitis.

PURPOSE: Changes in morbidity pattern of ulcerative colitis have created a need to update understanding of the course of the disease. METHOD: A follow-up study was done of relapse rates and progression of inflammation in 571 non-selected patients with ulcerative and indeterminate colitis. RESULTS: Relapse rate ten years after diagnosis was 70 percent in definite ulcerative colitis, 22 percent in probable ulcerative colitis, and 77 percent in indeterminate colitis. During the study period, there was no change in the relapse rate. In relapsing proctitis, 52 percent developed more extensive inflammation. Fifty-four percent of patients with only one attack of colitis had persistent signs of inflammatory bowel disease. CONCLUSIONS: Shift in morbidity pattern to a greater proportion of patients with proctitis at diagnosis and a shorter time from onset of symptoms to diagnosis had no influence on the relapse rate. Indeterminate colitis has a worse prognosis than definite ulcerative colitis. Considering the documented efficacy of sulfasalazine, the high relapse rate calls for studies of the effectiveness of such treatment in everyday practice.

Adolescent↗

Prostate-specific antigen in patients with relapsed prostate cancer following endocrine treatment.

We assessed the relationship between changes in PSA and prognosis, as a possible reflection of tumour growth in patients who relapse following primary endocrine therapy. In 8 patients in whom no therapeutic change was attempted after PSA relapse, the PSA level increased exponentially. Their PSA-DT had a close positive relationship to the duration of survival after relapse (r = 0.79, p = 0.02). In 6 patients who received chemotherapy after relapse, PSA-DT between PSA relapse and initiation of chemotherapy also had a relationship to the duration of survival after relapse (r = 0.87, p = 0.05). It appears to be reasonable to conclude from these findings that the PSA-DT value is regarded to be a factor associated with prognosis in cases with an exponential increase in PSA after replase.

Aged↗

Thyroglobulin, thyrotropin and thyrotropin binding inhibiting immunoglobulins assayed at the withdrawal of antithyroid drug therapy as predictors of relapse of Graves' disease within one year.

"Sensitive" thyrotropin (TSH), thyroglobulin (TG) and even thyrotropin binding inhibiting immunoglobulins (TBII) assays are now widely available. The objective of the present study was to determine the most accurate of these three parameters to predict the relapse of Graves' disease during the year following treatment discontinuation and to evaluate whether the assay of three markers is able to improve the prediction. TSH, TG and TBII were measured in the sera of 67 Graves' disease patients after at least 12 months of medical treatment. In 52 patients, TBII had also been determined before the beginning of the medical treatment. Under treatment, all the patients were clinically and biologically euthyroid, but in 9 goitrous patients it was impossible to lower the doses of carbimazole without an immediate relapse. The TSH levels of these 9 patients were still low in all cases but one; TG and TBII levels were abnormal in all. In the other 58 patients, the treatment was discontinued; 22 relapsed within one year, more frequently when a goiter was present. The most reliable parameter for the prediction of relapse was found to be TBII, as its specificity was high (94.5%), although its sensitivity was poor (45%); TG was more sensitive (64%) but far less specific (57%); TSH and "initial" TBII appeared to be of a little interest. When TBII was elevated prior to the withdrawal of treatment, the determination of TG was useful: abnormal values of both TBII and TG were always associated with a relapse. When TBII testing was negative, the relapse risk fell to 0.26, and to 0.08 when three criteria were matched: no goiter, negative TBII, normal TG.

Antibodies↗

The validity of the reinstatement model of craving and relapse to drug use.

RATIONALE: The reinstatement procedure has been used increasingly as a laboratory model of craving and relapse to drug abuse. With the number of reports involving this procedure growing, its validity as a model of relapse merits discussion. OBJECTIVES: The present commentary addresses the validity of the reinstatement procedure in relation to the following three types of models: 1) formal equivalence models, which are assessed on the basis of how well they resemble some phenomenon outside the laboratory (i.e. face validity); 2) correlational models, which are assessed on the basis of how well they predict outcomes of various interventions (such as drug administration or environmental change) when effected outside the laboratory (i.e. predictive validity); and 3) functional equivalence models, which are assessed on the basis of whether the laboratory phenomenon is mechanistically identical or reasonably similar to the phenomenon outside the laboratory (i.e. content validity). METHODS: In order to evaluate the reinstatement model, we briefly examined its various forms and uses, and compared preclinical outcomes to what is known about relapse from the clinical literature. RESULTS. In its most general form, the reinstatement model has reasonable face validity; that is, there is a general agreement in appearance or form of the behavior in the model and the clinical target, relapse. This face validity is generally absent for the procedure when it is used as a model of craving. The predictive validity of the model has not been established. Evidence from studies of treatments for drug relapse have not supported the validity of the model, however from studies of the effects of the presentation of various types of stimuli (e.g. drug "priming") there is mixed evidence supporting predictive validity. With regard to functional equivalence, there is reasonable evidence supporting functional commonalities between drug self-administration in laboratory animals and human drug abusers, which lends support to the validity of the reinstatement model. However, there are several specific areas of departure between the methods and results using the model and clinical practices and observations about relapse, suggesting a lack of functional equivalence. CONCLUSIONS: There is reasonable evidence to support the face validity of the model, but at this time, neither its predictive validity nor functional equivalence has been fully established, which underscores the need for caution in generalizing results from the model to the clinical condition.

Animals↗

The reinstatement model and relapse prevention: a clinical perspective.

OBJECTIVES: This commentary assesses the degree to which the reinstatement model is homologous to the human experience of relapse. RESULTS: A review of the literature suggests that the relationship is less clear than is often assumed, largely due to a lack of prospective data on the precipitants and process of relapse (especially relapse to heroin or cocaine abuse). However, reinstatement does not need to resemble relapse to have immediate clinical value; predictive validity as a medication screen would be sufficient. Whether the model has predictive validity is unknown, because, to date, very few clinical trials have tested medications that are effective in the reinstatement model, and even fewer have used designs comparable to those of reinstatement experiments. A clinical trial comparable to a reinstatement experiment would enroll participants who are already abstinent, and its main outcome measure would be propensity to undergo a specific type of relapse (e.g., relapse induced by stress or cues). CONCLUSIONS: Until clinical and preclinical work are more comparable, criticisms of the reinstatement model's presumed shortcomings are premature.

Animals↗

Splenectomy for immune thrombocytopenic purpura: long-term results and treatment of postsplenectomy relapses.

Information regarding prognostic determinants of outcome after splenectomy for adult immune thrombocytopenic purpura (ITP) and the management of postsplenectomy relapse is limited. Among 140 adult patients with ITP who had therapeutic splenectomy at our institution, 88% achieved either a complete (platelets > 150 x 10(9)/l) or a partial (platelets > or = 50 x 10(9)/l) response that was sustained for at least 1 month. At 3, 6, and 12 months after splenectomy, time-adjusted complete response rates were 77%, 71%, and 74%, respectively. The 5-year relapse-free survival was 75%; all but three relapses occurred within 2 years of splenectomy. In multivariate analysis, younger age and higher peak postsplenectomy platelet counts were significantly associated with a favorable response to splenectomy. None of several preoperative or perioperative variables was predictive of a relapse after an initial response to splenectomy. Corticosteroids, danazol, vincristine, and cyclophosphamide were often effective in the treatment of patients who were either refractory to or had a relapse after splenectomy. One patient responded to rituximab after not responding to corticosteroids, azathioprine, and vincristine. After a median follow-up of 37.5 months (range: 0-183) from splenectomy, there were 25 deaths, including 2 from postoperative complications, 1 from gastrointestinal bleeding related to thrombocytopenia, and 1 from overwhelming sepsis related to the splenectomized state. The current study provides additional data on both the long-term outcome of splenectomy in adults with ITP and the management of postsplenectomy relapse.

Adolescent↗

Donor lymphocyte infusions for relapse of chronic myeloid leukemia after allogeneic stem cell transplantation: prognostic significance of the dose of CD3(+) and CD4(+) lymphocytes.

Between December 1993 and November 2001, 30 patients with chronic myeloid leukemia who relapsed after stem cell transplantation were studied. Seventeen patients were not treated before donor lymphocyte infusion (DLI), eight patients received interferon-alpha (IFN-alpha), and five underwent chemotherapy. The method of DLI was the bulk dose regimen. The median time between DLIs was 6 weeks. The median number of infusions was three; the median time from transplant to relapse was 17 months and from relapse to DLI 2 months. Eleven patients (37%) were in molecular/cytogenetic relapse, 14 (47%) in chronic phase, and five (16%) in accelerated or blastic phase. Seventeen patients (57%) developed acute graft-versus-host disease (GVHD). Chronic GVHD was observed in 15 of 24 (62%) patients. Four (13%) patients developed cytopenia after a median of 30 days. Nineteen (63%) patients achieved response, 15 of them developed GVHD. The response rate according to the disease phase was molecular or cytogenetic relapse: 91%, chronic phase: 57%, and accelerated or blastic phase: 20%. The median time to response was 6 months. Patients treated with IFN-alpha or no treatment as well as those who were in molecular/cytogenetic relapse and those who received a CD3(+) cell dose <1 x 10(8)/kg and CD4(+) <8 x 10(7)/kg had better survival. We conclude that patients who receive lower doses of lymphocytes have better survival. In some patients IFN-alpha seems to be a good choice to potentiate the graft-versus-leukemia (GVL) effect.

Adolescent↗

High expression of costimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML).

Costimulatory molecules such as lymphocyte function-associated antigen (LFA)-1 (CD11a), LFA-3 (CD58), intercellular adhesion molecule (ICAM)-1 (CD54), neuronal cell adhesion molecule (NCAM) (CD56), B7-1 (CD80), or B7-2 (CD86) are important regulatory elements in healthy immunological cascades, but their role in acute myeloid leukemia (AML) has only been rarely investigated. We studied their expression on mononuclear bone marrow (BM) cells from 105 patients with AML at initial diagnosis and evaluated their prognostic significance. Fluorescence-activated cell sorter (FACS) analyses were performed using antibodies directly conjugated with fluorescein. A BM sample was considered positive if more than 20% of the cells in the blast containing gate expressed the respective marker. The surface expression of CD11a (27 of 29 cases positive with an average of 71% positive blasts; 27(+)/29, 71%), CD54 (23(+)/33, 37%), CD56 (24(+)/93, 20%), CD58 (29(+)/29, 95%), CD80 (13(+)/28, 30%), and CD86 (19(+)/29, 39%) was measured. The expression of these markers in different French-American-British (FAB) classification types (M0-M5) was heterogeneous, except for CD56, which showed a higher proportion of positive cells in monocytic subtypes of AML. In addition, cases with a "poor risk" karyotype as well as patients succumbing to "early death" after double induction therapy according to the AML Cooperative Group (CG) protocol were characterized by a high expression of CD56. Relapse-free survival analyses demonstrated that patients with more than 8% CD56(+) cells in the BM relapsed significantly sooner. CD54 was preferentially expressed in AML M4(eo) and in addition in "favorable" cytogenetic risk groups and in cases that had responded to AML-CG therapy. Only very high proportions (>60%) of CD54(+) cells were associated with a lower probability for relapse-free survival. CD80 and CD86 expressions were similar in all FAB types. Patients who had responded to AML-CG therapy showed higher CD80 proportions and lower CD86 proportions compared to the "nonresponder" group. Whereas cases with more than 15% CD80(+) cells had a significantly lower probability for relapse-free survival, only cases with more than 65% CD86(+) were characterized by a significantly lower probability for relapse-free survival. Expression profiles of CD11a and CD58 were not associated with specific FAB types or prognostically relevant groups. We can conclude: (1) Expression of costimulatory molecules in AML is very variable. This reflects the great diversity of immunophenotypes in AML. (2) CD56 is mainly expressed in monocytic subtypes of AML. CD56(+) subtypes of AML seem to be a separate entity with a worse prognosis independent of the karyotype. (3) High expression of some costimulatory molecules correlates with a worse prognosis concerning relapse-free survival times.

Antigens, CD↗

Early detection of relapse and evaluation of treatment for mixed chimerism using fluorescence in situ hybridization following allogeneic hematopoietic cell transplant for hematological malignancies.

In order to detect chimerism, fluorescence in situ hybridization (FISH) and cytogenetic analyses were performed on bone marrow cells from 47 patients with hematological malignancies following allogeneic hematopoietic cell transplant (HCT). The dual-color XY, major Bcr-Abl (M-Bcr-Abl), and specific alpha-satellite probes were used for sex-mismatched HCT, chronic myeloid leukemia (CML), and myelodysplastic syndrome (MDS) cases with karyotypic abnormalities before HCT, respectively. Donor cells were found using FISH analysis in all 32 cases examined within 2 months following HCT, confirming engraftment. In six cases, however, cytogenetic analysis failed to detect donor cells due to lack of metaphases. Relapse occurred in four of the six cases in which mixed chimerism was detected using FISH analysis after 6 months of HCT. In contrast, after 12 months of HCT, no relapse was found in 24 patients without host cells. For two patients with mixed chimerism, gradual reduction of immunosuppressants or donor lymphocyte infusion resulted in the disappearance of host cells as analyzed using FISH analysis. In three extramedullary relapse cases, however, cytogenetic relapse preceded morphological and FISH relapse. These findings suggest that FISH analysis is more useful for detecting residual host cells after HCT, and the combination of FISH and cytogenetic analyses provide a more detailed evaluation for HCT patients. The results also indicate that monitoring of mixed chimerism using FISH analysis after 6 months of HCT is important for allowing the early detection of hematological relapse.

Female↗