We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after... more We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after allogeneic bone marrow transplantation, who was treated by donor leukocyte infusions. We observed potent adoptive immunotherapy which produced a cytologic complete remission and total chimeric state. This was of short duration and the patient died of severe graft-versus-host disease. We present a short summary of
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the hematopoietic stem cell ... more Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the hematopoietic stem cell that makes blood cells more sensitive to the action of complement. Patients experience intravascular hemolysis, smooth muscle dystonia, renal failure, arterial and pulmonary hypertension, recurrent infectious diseases and an increased risk of notably dreadful thrombotic complications. The diagnosis is made by flow cytometry. Efforts have been recently performed to improve the sensitivity and the standardization of this technique. PNH is frequently associated with aplastic anemia or low-risk myelodysplasia and may be asymptomatic. Management of the classical form of PNH has been dramatically revolutionized by the development of eculizumab, which brings benefits in terms of hemolysis, quality of life, renal function, thrombotic risk, and life expectancy. Prophylaxis and treatment of arterial and venous thrombosis currently remain a challenge in PNH.
Objective: To date, only a small number of epidemiological studies on myelofibrosis have been per... more Objective: To date, only a small number of epidemiological studies on myelofibrosis have been performed. The current study aimed to characterize the myelofibrosis patient population in Belgium according to pre-defined disease parameters (diagnosis, risk categories, hemoglobin <10 g/dl, spleen size, constitutional symptoms, platelet count, myeloblast count), with a view to obtaining a deeper understanding of the proportion of patients that may benefit from the novel myelofibrosis therapeutic strategies. Methods: A survey was used to collect data on prevalence and disease parameters on all myelofibrosis patients seen at each of 18 participating hematologic centers in 2011. Aggregated data from all centers were used for analysis. Analyses were descriptive and quantitative. Results: A total of 250 patients with myelofibrosis were captured; of these, 136 (54%) were male and 153 (61%) were over 65 years old. One hundred sixty-five (66%) of myelofibrosis patients had primary myelofibrosis and 85 (34%) had secondary myelofibrosis. One hundred ninety-three myelofibrosis patients (77%) had a palpable spleen. About a third of patients (34%) suffered from constitutional symptoms. Two hundred twenty-two (89%) myelofibrosis patients had platelet count ≧50 000/μl and 201 (80%) had platelet count ≧100 000/μl. Of 250 patients, 85 (34%) had a myeloblast count ≧1%. Six (2%) patients had undergone a splenectomy. Thirteen (5·2%) patients had undergone radiotherapy for splenomegaly. Conclusions: The results of this survey provide insight into the characteristics of the Belgian myelofibrosis population. They also suggest that a large proportion of these patients could stand to benefit from the therapies currently under development.
To evaluate the anatomic and functional results of transperitoneal-transvesical repair of simple ... more To evaluate the anatomic and functional results of transperitoneal-transvesical repair of simple and complex vesicovaginal fistulas (VVFs). Between 1978 and 1995, 30 VVFs in 28 patients (mean age 44.6 years, range 21 to 80) were treated by way of a transperitoneal-transvesical approach. VVFs were secondary to hysterectomy in 67.8% of cases; 46.7% of VVFs were considered complex fistulas. Fifty percent of the VVFs were retrotrigonal and 40% were trigonal. A flap was interposed in 70% of cases. The vaginal fistula orifice was left open in 66% of cases, and 33% of VVFs required ureteral reimplantation. The mean duration of bladder drainage was 15.8 days (range 6 to 42), and the mean follow-up was 30 months (range 23 days to 14.6 years). The anatomic and functional results were evaluated by physical examination, cystoscopy, and a self-assessment questionnaire. Success was defined as the disappearance of the fistula. The overall success rate was 85% (24 of 28). The success rate was 87.5% for simple VVFs, 71% for complex VVFs, 93% for retrotrigonal VVFs, 66% for cervicotrigonal VVFs, and 80% for fistulas requiring ureteral reimplantation. Postoperative voiding disorders were reported in 38% of patients. Transperitoneal-transvesical repair of simple and complex VVFs remains the reference treatment for a disease that has become rare in countries with a well-developed healthcare system, but that is disabling and poorly tolerated by patients after the treatment of another disease.
Success in the management of urethral strictures can be claimed only after many years, patients s... more Success in the management of urethral strictures can be claimed only after many years, patients sometimes faring well for ten years or more before suffering a recurrence. We used endoscopic urethrotomy as primary treatment for a variety of urethral strictures in 123 patients. Follow-up is over two years for 63 patients and more than five years for 18. Over-all success rate at five years was 76 per cent. Failures are twice as frequent in strictures, regardless of their origin, involving the anterior urethra than in the bulbar or posterior urethra. Two-thirds occurred in the first year of follow-up, but, as in other techniques, recurrence can occur after four years.
We evaluated the results of renal transplantation in patients infected with Schistosoma haematobi... more We evaluated the results of renal transplantation in patients infected with Schistosoma haematobium, as well as the risks of urological complications and post-transplant reinfection. The outcome of 20 kidney transplants was retrospectively studied. Based on our experience and review of the literature, our clinical practice to prevent urological complications consisted of antischistosomal chemotherapy given at the pre-transplant evaluation, with endovesical ureteroneocystostomy preferred in case of bladder calcifications. A Foley catheter was maintained for 10 days. A transurethral bladder neck incision was performed before removal of the Foley catheter when bladder neck sclerosis was present. The 1 and 2-year patient survival rate was 93%, and 1 and 2-year graft survival rates were 88 and 81%, respectively, which were not different from those of a cohort of 167 patients without schistosomal infection. Surgical complications included 2 postoperative hemorrhages, 2 urinary leaks and 1 nonschistosomal related ureteral stricture. Post-transplant schistosomal infection never occurred when antischistosomal chemotherapy was given at the pre-transplant evaluation. Patients with schistosomal infection are suitable recipients for kidney transplantation, although they are at risk for urological complications. Unlike other infectious diseases, such as tuberculosis, the risk of recurrence due to reactivation of chronically hosted pathogens seems to be low or absent in patients who received antischistosomal chemotherapy at the pre-transplant evaluation. Long-term urological followup is recommended, including urethrocystoscopy, because of the theoretically increased risk for bladder malignancy.
We report our findings in 18 patients with acute lymphoblastic leukemia (ALL) aged 60 years or ol... more We report our findings in 18 patients with acute lymphoblastic leukemia (ALL) aged 60 years or older. A preleukemic syndrome was observed in 2 patients. Compared to younger adults with ALL, L3 morphology was unexpectedly frequent (4/16). T-ALL was not observed. Other criteria of poor prognosis (high white blood cell count, CNS involvement, organomegaly, high serum LDH) were similar to those reported in young adults. 12 patients were treated with an OPAL-derived regimen, 4 with the MAV regimen, 1 with vincristine and prednisone, 1 with 6-mercaptopurine. Complete remission was achieved in 8 patients but proved short-lived. 5 patients died in aplasia and 5 failed to achieve remission. Median survival for the whole group was 3 months. ALL in the elderly raises the dilemma of an aggressive disease in patients with poor tolerance to intensive therapy.
52 patients with refractory or relapsed acute myeloid leukaemia (AML) were randomly assigned to r... more 52 patients with refractory or relapsed acute myeloid leukaemia (AML) were randomly assigned to receive a combination of high-dose cytosine arabinoside (HD Ara-C), 3 g/m2/d and either mitoxantrone (MTX), 7 mg/m2/d (5 mg if older than 60 yr) or m-amsacrine (AMSA), 120 mg/m2/d (90 mg if older than 60 yr) for 5 d. The overall response rate was 50% and did not differ significantly in the two groups (46% for AMSA and 56% for MTX, p = 0.415). The median survival was 11 months (8 months for AMSA and 12 months for MTX, p = 0.326) and the median duration of complete remission (CR) was 11 months for AMSA and 12 months for MTX (p = 0.643). In relapsed patients, the only significant predictive factor for obtaining a complete response was the length of first complete remission. Patients with a first CR shorter than 6 months had a CR rate of 36% while it was 65% if the first CR lasted more than 6 months (p = 0.03). Severe (WHO grade III-IV) gastro-intestinal toxicity was more frequent in the AMSA group (27% vs 4%, p = 0.021). Treatment-related death occurred in 4 patients in the AMSA group and in 2 patients in the MTX group (p = 0.097). We conclude that neither of these two treatment modalities was shown to be superior in terms of CR rate and survival, with a better tolerance for MTX.
Aggressive non-Hodgkin's lymphoma is now often curable with chemotherapy. The Internation... more Aggressive non-Hodgkin's lymphoma is now often curable with chemotherapy. The International Prognostic Index (IPI) was recently developed to predict patient survival on the basis of pretreatment clinical features. However, classical multivariate regression models such as the IPI fail to detect time-dependent changes in the predictive value of covariates. In this study, an extension of the Cox proportional hazards model was used to determine whether the value of prognostic factors might decay over time. A total of 1271 patients younger than 60 years, entered on the LNH-84 and LNH-87 studies of an ACVBP induction regimen (consisting of doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, and IT methotrexate), were analyzed in terms of overall survival and monthly risk of dying. By a standard method, prognostic factors were identified in a training sample and confirmed in a validation sample. The independently significant covariates were then included in a step-function regression model (3-step) that permitted determination of their value in predicting the short term and long term survival of the entire population. During the entire follow-up period (median, 5.5 years), lactate dehydrogenase level, tumor stage, performance status, and number of extranodal sites remained independently predictive of overall survival. However, these covariates had nonproportional hazard functions. The study of their time-dependent effect with the 3-step model confirmed that they were predictive of overall survival during the short term follow-up period of 3 months to 2 years. However, during the induction period of 0-3 months and the long term follow-up period of 2-10 years, there was only 1 independently predictive factor for each of these periods: performance status and tumor stage, respectively. The IPI factors are relevant to short term follow-up and permit the selection of routine or experimental therapeutic regimens. In contrast, only performance status is predictive of a patient's ability to tolerate induction chemotherapy, and only tumor stage is predictive of long term survival.
Isochromosome of the long arm of chromosome 20 with interstitial loss of material [ider(20q)] is ... more Isochromosome of the long arm of chromosome 20 with interstitial loss of material [ider(20q)] is a rare cytogenetic abnormality reported in myelodysplastic syndrome (MDS), with neither specific morphological pattern nor clear prognostic significance. The aim of this retrospective multicentric study is to compare the peripheral blood and bone marrow morphology of MDS patients with ider(20q) (n = 13) and del(20q) (n = 21) and controls (n = 47) in order to investigate whether the ider(20q) harbors specific morphological features. The secondary objective is to compare the outcome of patients from both groups. This study performed on the largest cohort of MDS patients with ider(20q) is the first that identifies specific morphological features (hypogranulated and vacuolized neutrophils and neutrophil erythrophagocytosis) allowing the identification of this cytogenetic abnormality with high sensitivity (70%) and specificity (85.7%). Suspected ider(20q) by morphology should therefore support targeted FISH tests in case of non informative karyotype. This combined approach will allow a better estimation of the prevalence of this underdiagnozed entity. The overall survival and progression-free survival did not statistically differ in both groups. However, hypogranulated and vacuolized neutrophils were significantly associated with survival.
Acute leukaemia (AL) has been observed in association with Crohn&... more Acute leukaemia (AL) has been observed in association with Crohn's disease (CD) notably in patients treated with azathioprine (AZA), which is an immunosuppressant known for its carcinogenicity and in particular known to induce therapy-related acute myeloid leukaemia according to the 2008 WHO classification. Whereas the link between inflammatory bowel disease and AL has been well established, the exact role of AZA remains controversial. In this paper, we report the case of a 71-year-old white Caucasian male with CD treated for 7 years with AZA who developed an acute leukaemia. Chemotherapy was administered unsuccessfully and the patient died from this haematological disorder 9 months after diagnosis. We reviewed the current evidence on the interactions between CD, AL and AZA as well as the potential underlying mechanisms of leukaemia in AZA-treated patients. From this review, we concluded that AL should be questioned when facing cytopenia in a patient with CD. The nature of the association between AZA and AL in CD patients warrants further investigation.
We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after... more We report the case of a young patient with refractory acute lymphoblastic leukemia relapse, after allogeneic bone marrow transplantation, who was treated by donor leukocyte infusions. We observed potent adoptive immunotherapy which produced a cytologic complete remission and total chimeric state. This was of short duration and the patient died of severe graft-versus-host disease. We present a short summary of
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the hematopoietic stem cell ... more Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired disorder of the hematopoietic stem cell that makes blood cells more sensitive to the action of complement. Patients experience intravascular hemolysis, smooth muscle dystonia, renal failure, arterial and pulmonary hypertension, recurrent infectious diseases and an increased risk of notably dreadful thrombotic complications. The diagnosis is made by flow cytometry. Efforts have been recently performed to improve the sensitivity and the standardization of this technique. PNH is frequently associated with aplastic anemia or low-risk myelodysplasia and may be asymptomatic. Management of the classical form of PNH has been dramatically revolutionized by the development of eculizumab, which brings benefits in terms of hemolysis, quality of life, renal function, thrombotic risk, and life expectancy. Prophylaxis and treatment of arterial and venous thrombosis currently remain a challenge in PNH.
Objective: To date, only a small number of epidemiological studies on myelofibrosis have been per... more Objective: To date, only a small number of epidemiological studies on myelofibrosis have been performed. The current study aimed to characterize the myelofibrosis patient population in Belgium according to pre-defined disease parameters (diagnosis, risk categories, hemoglobin <10 g/dl, spleen size, constitutional symptoms, platelet count, myeloblast count), with a view to obtaining a deeper understanding of the proportion of patients that may benefit from the novel myelofibrosis therapeutic strategies. Methods: A survey was used to collect data on prevalence and disease parameters on all myelofibrosis patients seen at each of 18 participating hematologic centers in 2011. Aggregated data from all centers were used for analysis. Analyses were descriptive and quantitative. Results: A total of 250 patients with myelofibrosis were captured; of these, 136 (54%) were male and 153 (61%) were over 65 years old. One hundred sixty-five (66%) of myelofibrosis patients had primary myelofibrosis and 85 (34%) had secondary myelofibrosis. One hundred ninety-three myelofibrosis patients (77%) had a palpable spleen. About a third of patients (34%) suffered from constitutional symptoms. Two hundred twenty-two (89%) myelofibrosis patients had platelet count ≧50 000/μl and 201 (80%) had platelet count ≧100 000/μl. Of 250 patients, 85 (34%) had a myeloblast count ≧1%. Six (2%) patients had undergone a splenectomy. Thirteen (5·2%) patients had undergone radiotherapy for splenomegaly. Conclusions: The results of this survey provide insight into the characteristics of the Belgian myelofibrosis population. They also suggest that a large proportion of these patients could stand to benefit from the therapies currently under development.
To evaluate the anatomic and functional results of transperitoneal-transvesical repair of simple ... more To evaluate the anatomic and functional results of transperitoneal-transvesical repair of simple and complex vesicovaginal fistulas (VVFs). Between 1978 and 1995, 30 VVFs in 28 patients (mean age 44.6 years, range 21 to 80) were treated by way of a transperitoneal-transvesical approach. VVFs were secondary to hysterectomy in 67.8% of cases; 46.7% of VVFs were considered complex fistulas. Fifty percent of the VVFs were retrotrigonal and 40% were trigonal. A flap was interposed in 70% of cases. The vaginal fistula orifice was left open in 66% of cases, and 33% of VVFs required ureteral reimplantation. The mean duration of bladder drainage was 15.8 days (range 6 to 42), and the mean follow-up was 30 months (range 23 days to 14.6 years). The anatomic and functional results were evaluated by physical examination, cystoscopy, and a self-assessment questionnaire. Success was defined as the disappearance of the fistula. The overall success rate was 85% (24 of 28). The success rate was 87.5% for simple VVFs, 71% for complex VVFs, 93% for retrotrigonal VVFs, 66% for cervicotrigonal VVFs, and 80% for fistulas requiring ureteral reimplantation. Postoperative voiding disorders were reported in 38% of patients. Transperitoneal-transvesical repair of simple and complex VVFs remains the reference treatment for a disease that has become rare in countries with a well-developed healthcare system, but that is disabling and poorly tolerated by patients after the treatment of another disease.
Success in the management of urethral strictures can be claimed only after many years, patients s... more Success in the management of urethral strictures can be claimed only after many years, patients sometimes faring well for ten years or more before suffering a recurrence. We used endoscopic urethrotomy as primary treatment for a variety of urethral strictures in 123 patients. Follow-up is over two years for 63 patients and more than five years for 18. Over-all success rate at five years was 76 per cent. Failures are twice as frequent in strictures, regardless of their origin, involving the anterior urethra than in the bulbar or posterior urethra. Two-thirds occurred in the first year of follow-up, but, as in other techniques, recurrence can occur after four years.
We evaluated the results of renal transplantation in patients infected with Schistosoma haematobi... more We evaluated the results of renal transplantation in patients infected with Schistosoma haematobium, as well as the risks of urological complications and post-transplant reinfection. The outcome of 20 kidney transplants was retrospectively studied. Based on our experience and review of the literature, our clinical practice to prevent urological complications consisted of antischistosomal chemotherapy given at the pre-transplant evaluation, with endovesical ureteroneocystostomy preferred in case of bladder calcifications. A Foley catheter was maintained for 10 days. A transurethral bladder neck incision was performed before removal of the Foley catheter when bladder neck sclerosis was present. The 1 and 2-year patient survival rate was 93%, and 1 and 2-year graft survival rates were 88 and 81%, respectively, which were not different from those of a cohort of 167 patients without schistosomal infection. Surgical complications included 2 postoperative hemorrhages, 2 urinary leaks and 1 nonschistosomal related ureteral stricture. Post-transplant schistosomal infection never occurred when antischistosomal chemotherapy was given at the pre-transplant evaluation. Patients with schistosomal infection are suitable recipients for kidney transplantation, although they are at risk for urological complications. Unlike other infectious diseases, such as tuberculosis, the risk of recurrence due to reactivation of chronically hosted pathogens seems to be low or absent in patients who received antischistosomal chemotherapy at the pre-transplant evaluation. Long-term urological followup is recommended, including urethrocystoscopy, because of the theoretically increased risk for bladder malignancy.
We report our findings in 18 patients with acute lymphoblastic leukemia (ALL) aged 60 years or ol... more We report our findings in 18 patients with acute lymphoblastic leukemia (ALL) aged 60 years or older. A preleukemic syndrome was observed in 2 patients. Compared to younger adults with ALL, L3 morphology was unexpectedly frequent (4/16). T-ALL was not observed. Other criteria of poor prognosis (high white blood cell count, CNS involvement, organomegaly, high serum LDH) were similar to those reported in young adults. 12 patients were treated with an OPAL-derived regimen, 4 with the MAV regimen, 1 with vincristine and prednisone, 1 with 6-mercaptopurine. Complete remission was achieved in 8 patients but proved short-lived. 5 patients died in aplasia and 5 failed to achieve remission. Median survival for the whole group was 3 months. ALL in the elderly raises the dilemma of an aggressive disease in patients with poor tolerance to intensive therapy.
52 patients with refractory or relapsed acute myeloid leukaemia (AML) were randomly assigned to r... more 52 patients with refractory or relapsed acute myeloid leukaemia (AML) were randomly assigned to receive a combination of high-dose cytosine arabinoside (HD Ara-C), 3 g/m2/d and either mitoxantrone (MTX), 7 mg/m2/d (5 mg if older than 60 yr) or m-amsacrine (AMSA), 120 mg/m2/d (90 mg if older than 60 yr) for 5 d. The overall response rate was 50% and did not differ significantly in the two groups (46% for AMSA and 56% for MTX, p = 0.415). The median survival was 11 months (8 months for AMSA and 12 months for MTX, p = 0.326) and the median duration of complete remission (CR) was 11 months for AMSA and 12 months for MTX (p = 0.643). In relapsed patients, the only significant predictive factor for obtaining a complete response was the length of first complete remission. Patients with a first CR shorter than 6 months had a CR rate of 36% while it was 65% if the first CR lasted more than 6 months (p = 0.03). Severe (WHO grade III-IV) gastro-intestinal toxicity was more frequent in the AMSA group (27% vs 4%, p = 0.021). Treatment-related death occurred in 4 patients in the AMSA group and in 2 patients in the MTX group (p = 0.097). We conclude that neither of these two treatment modalities was shown to be superior in terms of CR rate and survival, with a better tolerance for MTX.
Aggressive non-Hodgkin's lymphoma is now often curable with chemotherapy. The Internation... more Aggressive non-Hodgkin's lymphoma is now often curable with chemotherapy. The International Prognostic Index (IPI) was recently developed to predict patient survival on the basis of pretreatment clinical features. However, classical multivariate regression models such as the IPI fail to detect time-dependent changes in the predictive value of covariates. In this study, an extension of the Cox proportional hazards model was used to determine whether the value of prognostic factors might decay over time. A total of 1271 patients younger than 60 years, entered on the LNH-84 and LNH-87 studies of an ACVBP induction regimen (consisting of doxorubicin, cyclophosphamide, vindesine, bleomycin, methylprednisolone, and IT methotrexate), were analyzed in terms of overall survival and monthly risk of dying. By a standard method, prognostic factors were identified in a training sample and confirmed in a validation sample. The independently significant covariates were then included in a step-function regression model (3-step) that permitted determination of their value in predicting the short term and long term survival of the entire population. During the entire follow-up period (median, 5.5 years), lactate dehydrogenase level, tumor stage, performance status, and number of extranodal sites remained independently predictive of overall survival. However, these covariates had nonproportional hazard functions. The study of their time-dependent effect with the 3-step model confirmed that they were predictive of overall survival during the short term follow-up period of 3 months to 2 years. However, during the induction period of 0-3 months and the long term follow-up period of 2-10 years, there was only 1 independently predictive factor for each of these periods: performance status and tumor stage, respectively. The IPI factors are relevant to short term follow-up and permit the selection of routine or experimental therapeutic regimens. In contrast, only performance status is predictive of a patient's ability to tolerate induction chemotherapy, and only tumor stage is predictive of long term survival.
Isochromosome of the long arm of chromosome 20 with interstitial loss of material [ider(20q)] is ... more Isochromosome of the long arm of chromosome 20 with interstitial loss of material [ider(20q)] is a rare cytogenetic abnormality reported in myelodysplastic syndrome (MDS), with neither specific morphological pattern nor clear prognostic significance. The aim of this retrospective multicentric study is to compare the peripheral blood and bone marrow morphology of MDS patients with ider(20q) (n = 13) and del(20q) (n = 21) and controls (n = 47) in order to investigate whether the ider(20q) harbors specific morphological features. The secondary objective is to compare the outcome of patients from both groups. This study performed on the largest cohort of MDS patients with ider(20q) is the first that identifies specific morphological features (hypogranulated and vacuolized neutrophils and neutrophil erythrophagocytosis) allowing the identification of this cytogenetic abnormality with high sensitivity (70%) and specificity (85.7%). Suspected ider(20q) by morphology should therefore support targeted FISH tests in case of non informative karyotype. This combined approach will allow a better estimation of the prevalence of this underdiagnozed entity. The overall survival and progression-free survival did not statistically differ in both groups. However, hypogranulated and vacuolized neutrophils were significantly associated with survival.
Acute leukaemia (AL) has been observed in association with Crohn&... more Acute leukaemia (AL) has been observed in association with Crohn's disease (CD) notably in patients treated with azathioprine (AZA), which is an immunosuppressant known for its carcinogenicity and in particular known to induce therapy-related acute myeloid leukaemia according to the 2008 WHO classification. Whereas the link between inflammatory bowel disease and AL has been well established, the exact role of AZA remains controversial. In this paper, we report the case of a 71-year-old white Caucasian male with CD treated for 7 years with AZA who developed an acute leukaemia. Chemotherapy was administered unsuccessfully and the patient died from this haematological disorder 9 months after diagnosis. We reviewed the current evidence on the interactions between CD, AL and AZA as well as the potential underlying mechanisms of leukaemia in AZA-treated patients. From this review, we concluded that AL should be questioned when facing cytopenia in a patient with CD. The nature of the association between AZA and AL in CD patients warrants further investigation.
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Papers by Christian Chatelain