Factors influencing severe cytopenia in chronic phase chronic myeloid leukemia patients receiving initial second generation tyrosine kinase inhibitors and its impact on treatment responses and outcomes / 中华血液学杂志

Objective: To explore the influencing covariates of severe neutrophils and/or thrombocytopenia and their effect on treatment response and outcome in patients with chronic-phase chronic myeloid leukemia (CP-CML) receiving initial second-generation tyrosine kinase inhibitors (2G-TKI) . Methods: Data from consecutive patients aged ≥18 years with newly diagnosed CP-CML who received initial 2G-TKI at Peking University People's Hospital from September 2008 to November 2021 were interrogated. Binary logistic regression models and Fine-Gray and Cox regression models were applied. Results: Data from 267 patients who received initial 2G-TKI, including nilotinib (n=239, 89.5% ) and dasatinib (n=28, 10.5% ) , were interrogated. The median age was 36 (range, 18-73) years, and 156 (58.4% ) patients were male. At a median treatment period of 1.0 (0.1-3.0) month, 43 (16.1% ) patients developed grade ≥3 neutrophils and/or thrombocytopenia and recovered within 1.0 (0.1-24.6) month. Male (OR=2.9, 95% CI 1.2-6.8; P=0.018) , age of ≥36 years (OR=3.2, 95% CI 1.4-7.2, P=0.005) , a spleen below a costal margin of ≥7 cm (OR=2.8, 95% CI 1.2-6.6, P=0.020) , and a hemoglobin (HGB) level of <100 g/L (OR=2.9, 95% CI 1.3-6.8, P=0.012) at diagnosis were significantly associated with grade ≥ 3 neutrophils and/or thrombocytopenia. Based on their regression coefficients, male, age of ≥36 years, a spleen below a costal margin of ≥7 cm, and an HGB level of <100 g/L were given 1 point to form a predictive system. All patients were divided into three risk subgroups, and the incidence of severe cytopenia significantly differed among the three groups (P < 0.001) . Grade ≥3 neutrophils and/or thrombocytopenia for >2 weeks was significantly associated with lower cumulative incidences of complete cytogenetic response (CCyR, HR=0.5, 95% CI 0.3-0.7, P<0.001) and major molecular response (MMR, HR=0.4, 95% CI 0.3-0.8, P=0.004) and was not significantly associated with failure, progression, and survival. Conclusion: Male, advanced age, a large spleen, and a low HGB level were significantly associated with severe cytopenia. The four covariates were used to establish a prediction model, in which the incidence of severe cytopenia among different risk groups was significantly different. Severe cytopenia for >2 weeks was a negative factor for responses but not for outcomes.

Inhibiteurs de la tyrosine kinase dans le traitement de la leucemie myeloide chronique : experience du Niger

INTRODUCTION. La leucemie myeloide chronique (LMC) est une proliferation monoclonale maligne des cellules sanguines due a la presence du chromosome Philadelphie (ch Ph) ou du transcrit BCR-ABL a la biologie moleculaire (BM). Dans ce travail nous rapportons l'experience de l'utilisation des Inhibiteurs de la Tyrosine Kinase (TKIs) dans la LMC au Niger. PATIENTS ET MeTHODES. Il s'agit d'une etude retrospective realisee en oncohematologie et en Medecine Interne de l'HNN de janvier 2009 a septembre 2015 (6 ans) ou 15 patients etaient suivis pour LMC et traites par TKIs. Les aspects epidemiologiques; therapeutiques et pronostiques ont ete evalues. RESULTATS. L'age moyen au diagnostic etait de 46;7 ans (extremes : 19 a 68) avec une predominance masculine (9 cas/15). La splenomegalie etait retrouvee dans 100% des cas. Le taux moyen de l'hemoglobine; des leucocytes et des plaquettes etaient respectivement de 9;35 g/dl (extremes : 6-12;1); 296 G/L (extremes : 85-342) et 575 G/L (extremes : 158-740). Le transcrit de type BCR-ABL b2a2 b3a2 etait present dans huit cas; le BCR-ABL b2a2 b3a3 dans un cas et six cas avaient le Ch Ph. Un patient est decede avant la mise sous Imatinib et les 14 autres ont une reponse hematologique complete. Un cas a repondu au controle lors de la BM realisee chez deux patients et le non repondant a ete mis sous Dasatinib. Une patiente a rapporte une photosensibilite et une dyspnee sous Imatinib. CONCLUSION. Les TKIs sont efficaces dans le traitement de la LMC mais ne sont pas disponibles au Niger que lorsque la BM confirme le diagnostic

Multivariate analysis of imatinib resistance-related factors during the treatment of chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To explore efficacy of imatinib for patients with chronic myeloid leukemia(CML) and its resistance-related factors during the treatment.</p><p><b>METHODS</b>The clinical data of 214 CML patients received imatinib were analyzed respectively in our hospital from April 2005 to December 2010. The therapy history and efficacy of regular follow-up and factors influencing drug resistance were analyzed. COX regression analysis was used to perform the univariate and multivariate analysis.</p><p><b>RESULTS</b>Until the end of follow up, thirty-one patients (14.5%) occurred drug resistance. One of them was in accelerated phase(AP), and two in blast phase(BP); 69.2% of patients achieved a complete cytogenetic response(CCyR), and 31.3% of patients achieved a major molecular response(MMR). COX analysis was performed in 207 chronic phase(CP) patients. Univariate analysis showed that the course of disease before treatment, the hemoglobin count, the white blood cell count, whether achieved CCyR or not and whether achieved MMR or not were the influencing factors for imatinib resistance. Multivariate analysis showed that whether achieved CCyR or not was the independent factor for drug resistance.</p><p><b>CONCLUSION</b>Whether achieved CCyR or not is an independent factor and also a protective factor for imatinib resistance in patients with CML.</p>

Preliminary comparison of efficacy and safety of dasatinib and imatinib in newly diagnosed chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy and safety of dasatinib and imatinib in patients with newly diagnosed chronic phase chronic myeloid leukemia (CML-CP).</p><p><b>METHODS</b>37 CML-CP patients were randomized to receive dasatinib 100 mg orally daily or imatinib 400 mg orally daily. The efficacy and safety data were collected and compared.</p><p><b>RESULTS</b>Of 37 CML-CP patients, 18 received dasatinib and 19 received imatinib. The both of median duration of drug therapy and follow-up were 38 months. (1) The rate of complete cytogenetic response (CCyR) at 12 months was higher in dasatinib group than in imatinib group (89% vs 68%), but there was no significantly statistic significance between two groups (P = 0.232). The cumulative CCyR rate by 36 months was 89% in both arms. The major molecular response (MMR) at 18 months was 76% in dasatinib arm, being significantly higher than that in imatinib arm (37%) (P = 0.017). The cumulative MMR rate by 36 months was 82% versus 68% in dasatinib or imatinib (P = 0.694). The median time to CCyR and MMR was significantly faster for dasatinib than for imatinib (3 months vs. 6 months, and 14 months vs. 34 months, respectively). (2) The drug-related adverse events were mostly grade 1/2 and were well-tolerated. Increase of serum glutamic pyruvic transaminase, pleural effusion and thrombocytopenia were more common in dasatinib arm, while hypophosphatemia, edema and neutropenia were more common in imatinib arm.</p><p><b>CONCLUSION</b>Dasatinib is an effective and safe therapy option and can be used as first-line therapy for newly diagnosed CML-CP patients.</p>

Meta-analysis of imatinib mesylate with or without interferon for chronic-phase chronic myeloid leukemia / 中华血液学杂志

<p><b>OBJECTIVE</b>Meta-analysis of the efficiencies of imatinib mesylate (IM) with or without interferon for chronic myeloid leukemia-chronic phase (CML-CP) patients.</p><p><b>METHODS</b>Published studies of IM with or without interferon for CML-CP patients as first-line therapy were collected from PubMed, Cochrane Central Register of Controlled Trials (CENTRAL) of the Cochrane Library, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), VIP information and WANFANG database. References of retrieved articles were also identified. The quality of each randomized controlled trial (RCT) was evaluated by the Cochrane collaboration's tool for assessing the risk of bias. Data analysis was performed with RevMan 5.1.</p><p><b>RESULTS</b>A total of 5 articles involving 1754 patients were included. Meta-analysis results showed that there were no statistical differences between IM with interferon and IM monotherapy for the complete cytogenetic response (CCyR) rate at 12 months,but IM with interferon could improve major molecular response (MMR) rate at 12 months (OR=1.57, 95% CI: 1.26-1.96, P=0.02). Furthermore, IM combined with pegylated-interferon demonstrated superiority for MMR at 12 months (OR=2.43, 95% CI: 1.78-3.33, P<0.01).</p><p><b>CONCLUSION</b>Combination of IM and interferon does not increase CCyR rate, but improve MMR rate at 12 months.</p>

Karyotypic findings in chronic myeloid leukemia cases undergoing treatment.

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative expansion of primitive hematopoietic progenitor cells. MATERIALS AND METHODS: In the present study, CML samples were collected from various hospitals in Amritsar, Jalandhar and Ludhiana. RESULTS: Chromosomal alterations seen in peripheral blood lymphocytes of these treated and untreated cases of CML were satellite associations, double minutes, random loss, gain of C group chromosomes and presence of marker chromosome. No aberrations were observed in control samples. Karyotypic abnormalities have also been noted in the Ph-negative cells of some patients in disease remission. CONCLUSION: This is a novel phenomenon whose prognostic implications require thorough and systematic evaluation.

Mecanismos genéticos e epigenéticos relacionados com a resposta e a resistência à terapia com inibidores tirosina quinase na leucemia mielóide crônica / [Genetic and epigenetic mechanisms related to response and resistance to tyrosine kinase inhibitor therapy in myeloid leukemia chronic]

O tratamento da leucemia mieloide crônica (LMC) foi radicalmente modificado com a introdução dos inibidores de tirosina quinase (ITK) na prática clínica. Entretanto, a resistência aos ITK é um problema clínico crescente que acomete 35% dos pacientes com LMC em fase crônica (FC). Dentre os mecanismos envolvidos na resistência, se destaca a presença de mutações no domínio quinase (DQ) da proteína BCR-ABL. Porém, estas mutações ocorrem em 30­60% dos pacientes resistentes, evidenciando a heterogenidade dos mecanismos subjacentes ao aparecimento da resistência. Processos epigenéticos, como a metilação do DNA, modificação de histonas e expressão de microRNAs (miRNAs) ainda não foram amplamente estudados em relação à resistência na LMC. Os miRNAs, pequenos RNAs que regulam a expressão gênica, têm surgido recentemente como um mecanismo epigenético importante na fisiologia do câncer. O objetivo principal deste trabalho foi analisar os padrões de resposta de um grupo de pacientes com LMC submetidos à terapia com Imatinibe (IM), visando identificar mecanismos genéticos e epigenéticos relacionados com a resposta e a resistência aos ITK. Para isto, foram estudados 264 pacientes com LMC tratados com IM por um tempo médio de 30 meses (6-123), com 70% dos casos utilizando o inibidor por >12 meses. As taxas de resposta foram de 76% de resposta citogenética completa (RCgC), 63% de resposta molecular maior (RMM) e 29% de resposta molecular completa (RMC) nos pacientes com LMC-FC. Foi identificado um grupo de respondedores tardios, que representam ~30% dos pacientes que não alcançaram uma RCgC e/ou RMM nos tempos ótimos após inicio do IM. Um grupo de 126 pacientes foi selecionado para pesquisa de mutações no DQ. A presença de mutações foi avaliada por sequenciamento direto, por um ensaio de PCR alelo específico (PCR-AS) para detecção da mutação T315I e a quantificação dos clones mutados foi realizada por pirosequenciamento. Dos casos analisados, 23% apresentaram mutações no DQ. As mutações mais frequentes foram T315I (20%) e F359I/V (11,4%). A quantificação realizada por piro-sequenciamento forneceu informações complementares relevantes sobre o papel do tamanho do clone mutado na resposta ou resistência. Em um grupo de 17 pacientes, selecionados de acordo à resposta obtida com IM, foi realizada uma análise do perfil de expressão de miRNAs maduros através de arrays de TLDA (do inglês TaqMan Low Density Array). Foi identificado um grupo de 4 miRNAs diferencialmente expressos ao diagnóstico quando comparados os grupos de pacientes com resposta ao IM vs resistentes ao IM: miR-155, -451, -18b, -125a-5p. Um grupo de 29 miRNAs apresentou um padrão similar de variação da expressão durante o tratamento. Os níveis de expressão dos miR-451 e miR-148a mostraram uma correlação inversa com a carga tumoral aferida pelos níveis do transcrito BCR-ABL. Esta correlação foi mais consistente para o miR-148a. As análises in silico para predição de alvos para o miR148a indicaram 6 alvos potencialmente relacionados com a LMC: os genes E2F3, PIK3R3, IKKα, IKKß, p27Kip e SHP-2. Foi comprovado que a expressão do miR-148a em linhagens celulares de LMC está regulada por metilação do DNA.

Frequencies of BCR-ABL1 fusion transcripts among Sudanese chronic myeloid leukaemia patients

The incidence of one or other rearrangement in chronic myeloid leukemia (CML) patients varies in different reported series. In this study we report the frequencies of BCR-ABL1 fusion transcript variants studied in 43 CML patients from Sudan. The study includes 46 Sudanese patients, three of which negative for the BCR-ABL1 fusion transcript. More than half of 43 positive patients showed b2a2 fusion transcript (53.5 percent), while (41.9 percent) showed b3a2 transcript and the remaining (4.6 percent) coexpression of b3a2/ b2a2 and b3a2/b2a2/e19a2. We detected neither coexpression of p210/p190 nor e1a2 alone. Male patients showed a tendency to express b2a2, while female tende to express b3a2 (p = 0.017). Moreover, a single nucleotide polymorphism was detected in BCR exon 13 in one out of four patients and this patient showed only b2a2 expression. In conclusion, we observed a significant correlation between sex and type of BCR-ABL1 transcript, an observation that deserves further investigation.

Preliminary study of proteins related to blast crisis in chronic myeloid leukemia / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To identify and compare the expression profiles of differential proteins between chronic phase and blast crisis in chronic myeloid leukemia (CML) by proteomic analysis, and screen the proteins related to blast crisis.</p><p><b>METHODS</b>The total cellular proteins from the bone marrow cells at chronic phase (CP) and blast crisis (BC) in CML were separated by two-dimensional polyacrylamide gel electrophoresis (2-DE) and analyzed with ImageMaster 5.0 software to screen the differential protein spots. Differential protein spots were identified by mass spectrometry for peptide mass fingerprint in combination with database searching from SWISS-PROT. Then 3 protein spots were selected to verify at protein and mRNA levels by Western blot and semi-quantitative RT-PCR, separately.</p><p><b>RESULTS</b>Comparing gel pages from CML-CP and CML-BC, the expression of 13 protein spots decreased and 25 protein spots increased significantly in CML-BC. Twenty differential protein spots were identified by mass spectrometry and 15 were successfully determined. The results of Western blotting were similar to those of 2-DE and showed a high expression of hnRNPK, annexin A1 and RhoA. Semi-quantitative RT-PCR analysis showed that there was no correlation between the protein expression changes and mRNA levels of hnRNPK, annexin A1 and RhoA.</p><p><b>CONCLUSION</b>A group of proteins associated with blast crisis are obtained and the results may provide clues for further research to elucidate the role of these proteins in CML-BC carcinogenesis and to develop potential associated biomarkers.</p>

Abnormal chromatin clumping in leucocytes of Ph positive chronic myeloid leukemia cases - extending the morphological spectrum.

The syndrome of abnormal chromatin clumping is largely a morphological entity characterized by exaggerated chromatin clumping seen in the neutrophils. According to the recent World Health Organization (WHO) classification, it is categorized as a variant of atypical chronic myeloid leukemia (aCML) or Ph-negative CML. Most of the cases reported in literature have been negative for the Ph chromosome or the BCR-ABL gene. Till date, Ph positivity has been demonstrated in just one case. We report two more Ph-positive CML cases with abnormal chromatin clumping in neutrophils. To the best of our knowledge, this is only the second time in literature that such cases have been described. These two unusual cases go on to extend the morphological spectrum of granulocytic changes seen in Ph-positive CML.

Nonmyeloablative peripheral blood stem cell transplantation for chronic myeloid leukemia in chronic and accelerated phases / 中国实验血液学杂志

The aim of this study was to investigate the effect of nonmyeloablative peripheral blood stem cell transplantation in treatment of chronic myeloid leukemia in chronic phase (CML-CP) and accelerated phase (CML-AP). 24 patients with CML including 16 in CML-CP and 8 in CML-AP were treated with nonmyeloablative conditioning regimen for peripheral blood stem cell transplantation (PBHSCT). The conditioning regimen included fludarabine (30 mg/m(2)x6 d), busulphan [4 mg/(kg.d)x2 d] and CTX [350 mg/(m2.d)x2 d] combined with or without Ara-C. The donors were HLA-identical (n=20) and 5/6 antigen-matched (n=4). The dynamic observation of hematopoietic recovery in all patients was carried out. The results indicated that all the patients were successfully engrafted. The mean time for increase of the number of neutrophils to more than 0.5x10(9)/L and platelet more than 20x10(9)/L were 13 days and 11.5 days respectively. Out of 12 patients, 9 patients showed complete donor chimerism and 3 patients showed mixed chimerism at 30 days after transplantation. At 180 days after transplantation, 18 survival patients showed complete donor chimerism. 18 patients remained alive after a median follow-up length of 24 months (4-48 months). 2 cases died of severe acute GVHD and 1 case died of chronic GVHD, 2 cases died of interstitial pneumonia and 1 case died of relapsed. In conclusions, nonmyeloablative peripheral blood stem cell transplantation is an effective therapeutic method for CML patients in chronic phase and accelerated phase.

Therapeutic effects of imatinib on chronic myeloid leukemia in different phases and the factors affecting the effects / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the therapeutic effect of imatinib on chronic myeloid leukemia (CML) in different phases and analyze the factors that may affect the effects.</p><p><b>METHODS</b>Eighty-five patients with CML in chronic phase, 24 in accelerated phase and 19 in blastic phase patients were treated with imitinib. The hematologic response, cytogenetic response, molecular response, overall survival (OS), progression-free survival (PFS) and adverse events were analyzed in these groups.</p><p><b>RESULTS</b>The rates of complete hematologic response (CHR), complete cytogenetic response (CCyR) and complete molecular response (CMoR) of the patients in chronic phase were 100%, 82.4% and 21.2%, respectively, and the 5-year OS and PFS of these patients were 92.1% and 84.7%. All these rates were significantly higher than those in patients in accelerated and blastic phases (P<0.0001). The CCyR, CMoR, 5-year OS and PFS in the 42 newly diagnosed patients in chronic phase were 92.9%, 26.3%, 100% and 95.2%, respectively, all significantly higher than those in patients with interferon therapy failure (P<0.001). Severe leukocytopenia and thrombocytopenia occurred at greater frequencey in AP and BP patients than in chronic phase patients (P<0.0001). Non-hematologic toxicity was rarer and milder in patients in chronic phase. Multivariate analysis showed that interferon therapy prior to imitinib treatment and prolonged drug cessation were the independent factors that affected the achievement of cytogenetic response and PFS.</p><p><b>CONCLUSION</b>Early imitinib therapy can be effective and safe, and should be used as the first line drug for CML.</p>

Evaluation of early hospital discharge after allogeneic bone marrow transplantation for chronic myeloid leukemia

CONTEXT AND OBJECTIVE: The increasing number of patients waiting for bone marrow transplantation in our service led to the implement of an early hospital discharge program with the intention of reducing the interval between diagnosis and transplantation. In this study we analyzed the results from early discharge, with outpatient care for patients with chronic myeloid leukemia who underwent allogeneic bone marrow transplantation. DESIGN AND SETTING: Retrospective study at the Bone Marrow Transplantation Unit of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo. METHODS: We compared clinical outcomes within 100 days post-transplantation, for 51 patients with chronic myeloid leukemia (CML) who received partially outpatient-based allogeneic hematopoietic stem cell transplantation, and the results were compared with a historical control group of 49 patients who received inpatient-based hematopoietic stem cell transplantation. RESULTS: There were significantly fewer days of hospitalization (p = 0.004), Pseudomonas-positive cultures (p = 0.006) and nausea and vomiting of grade 2-3 (p < 0.001) in the outpatient group. There were no significant differences in mortality between the groups and no deaths occurred within the first 48 days post-transplantation in the outpatient group. CONCLUSIONS: This partially outpatient-based hematopoietic stem cell transplantation program allowed an increased number of transplantations in our institution, in cases of CML and other diseases, since it reduced the median length of hospital stay without increasing morbidity and mortality.

CONTEXTO E OBJETIVO: O número crescente de pacientes com indicação de transplante de medula óssea levou à implantação da alta hospitalar precoce em nosso serviço, com o intuito de reduzir o intervalo entre o diagnóstico e o transplante. Neste trabalho, avaliamos os resultados da alta precoce, com acompanhamento ambulatorial dos pacientes submetidos ao transplante de medula óssea alogênico portadores de leucemia mielóide crônica. TIPO E ESTUDO E LOCAL: Estudo retrospectivo, realizado no Serviço de Transplante de Medula Ossea do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. MÉTODOS: Foram avaliados os resultados do transplante de medula óssea alogênico, de doadores aparentados, até o dia 100 pós-transplante, de 51 pacientes portadores de leucemia mielóide crônica que receberam alta precoce, antes da pega medular. Os resultados foram comparados com o controle histórico constituído por 49 pacientes que receberam alta somente após a pega medular. RESULTADOS: Houve significativamente menos dias de hospitalização (p = 0,004), culturas positivas para Pseudomonas sp. (p = 0,006) e náusea e vômitos graus 2-3 (p < 0,001) no grupo de alta precoce. Não houve diferença significativa entre os grupos quanto à mortalidade e não ocorreu nenhum óbito até o dia 48 pós-transplante no grupo de alta precoce. CONCLUSÕES: O programa de alta precoce permitiu aumento do número de transplantes em leucemia mielóide crônica e outras doenças em nosso serviço, com redução do número de dias de internação hospitalar sem aumento da morbidade ou da mortalidade.

Report of 8 cases of bcr-abl gene positive thrombocytosis and review of the literature / 中华血液学杂志

<p><b>OBJECTIVE</b>To analyse the features of 8 cases of Bcr(+) thrombocytosis.</p><p><b>METHODS</b>The clinical and hematological features and therapeutic outcomes were studied retrospectively in 8 Bcr(+) thrombocytosis and compared with essential thrombocytosis (ET) and chronic myeloid leukemia-chronic phase thrombocytosis (CML-CP-T). BCR-ABL fusion gene was detected with PCR.</p><p><b>RESULTS</b>(1) Except for the presence of BCR-ABL fusion gene, there was no significant difference in clinical and hematological features and therapeutic outcomes between thrombocytosis with or without BCR-ABL. (2) The Bcr(+) thrombocytosis differed from CML-CP-T in the following aspects: female predominance, milder or no splenomegaly, peripheral leukocytes count < 40 x 10(9)/L, less or no basophilia and fewer immature granulocytes in peripheral blood, bone marrow granulocytic and/or megakaryocytic lineage hyperplasia, normal or increased neutrophil alkaline phosphatase score and less blastic transformation.</p><p><b>CONCLUSION</b>Bcr(+) thrombocytosis may be considered as a new member of chronic myeloproliferative diseases, a variant of essential thrombocythemia.</p>

Analysis of cytogenetic response in Ph+ chronic myeloid leukemia patients treated with interferon alpha / 中国实验血液学杂志

Ph chromosome occurs in nearly all patients with CML, and eliminating Ph-positive clone is a major target in the treatment of CML. IFN-alpha is a well-known effective treatment in chronic phase CML. The cytogenetic response and the prognostic factors in 128 CML patients treated with IFN-alpha were retrospectively studied. IFN-alpha administered singly at a dose of 3 million U/day for 2 - 3 times a week or in combination with either hydroxyurea (Hu), busulfan (Bu), low dose Ara-C or harringtonine. Karyotyping was examined by G-banding before and after IFN-alpha-based treatment. The results showed that all patients achieved complete hematological remission. Cytogenetic response occurred in 36 of 118 patients with standard t (9;22) translocation; 3 of these 36 patients had a complete cytogenetic response (Ph = 0), 13 had major cytogenetic responses (Ph < 35%) and 20 had minimal response (Ph > 35%). The total cytogenetic effectiveness was 13.6% (16/118). Four of seven patients with complicated variant translocation also achieved cytogenetic response, 2 of them had a major cytogenetic response and 2 had minimal response. Factors influenced the prognosis associated with cytogenetic response included sex, patient status at diagnosis and IFN-alpha administered singly or in combination with other chemotherapeutic agents. IFN-alpha could not prevent the progression of CML. It is concluded that Ph(+)CML patients with both standard and variant translocation had major cytogenetic response to IFN-alpha treatment at a dose of 6 - 9 million U/week in single or combination with Hu/Bu, however, IFN-alpha treatment could not prevent disease progression. Long term survival was also observed in patients with variant translocation treated with IFN-alpha. Regular cytogenesis examination in CML patients is necessary during IFN-alpha therapy, which is useful to reflect curative effect and progression of the disease.

Sumary of the duration of the phase transfer of chronic myeloid leukemia

A restrospective study carried out on 309 patients with chronic myelogenous leukemia treated from 1990 to 10/2000 showed that; -88 cases (28.3%) converted to the blast crisis. - 89.77% of these cases developed acute myeloblastic leukemia (AML) and 9.09% developed ALL.-The percentage of male and female were 55.68% and 44.31% - 45.45% of these converted cases occurred in the age group of 30-50. The youngest age was 10 months and the oldest age was : 72 years old. Mean of duration of the chronic phase was 2.5 years.

Leucemia mieloide crónica: evaluación de los resultados del tratamiento con interferón alfa / Chronic myeloid leukemia: evaluation of the results of the treatment with interferon alpha

El pronóstico de la leucemia mieloide crónica (LMC) mejoró substancialmente con el tratamiento con Interferón alfa (IFNalfa) y los mejores resultados estarían relacionados a la respuesta genética (RG). Para evaluar tal presunción, se compararon los resultados terapéuticos obtenidos en 30 pacientes con LMC Ph+ en primera fase crónica, tratados con IFN alfa 5 MU/M²/d (Grupo 1) con los resultados obtenidos en 31 pacientes pertenecientes a un protocolo previo basado en IFN alfa 3 MU 3/v/sem., más 6-mercapto purina 150mg/d/v.o. y citarabina 150 mg/d/sc por cuatro días por mes (Grupo 2). El Grupo 1 tuvo mejores respuestas hematológicas completas (80 por ciento) y RG (76 por ciento) que el Grupo 2 (29 por ciento y 17 por ciento respectivamente) (p < 0.001). La duración de la fase crónica fue más larga en el Grupo 1, 43 meses contra 18 meses en el Grupo 2 (p < 0.001). Además, la probabilidad de sobrevida a 5 años (SV) fue mejor en el Grupo 1, 62 por ciento contra 15 por ciento en el Grupo 2 (p < 0.001). En nuestra experiencia, 5 MU/M²/d de IFN alfa prolongó la SV y la duración de la fase crónica, independientemente de la RG, sugiriendo que los beneficios del IFN alfa podrían relacionarse a otros mecanismos de acción, además de la supresión del cromosoma Ph.

Unusual presentation of amoebic liver abscess as myeloid leukemoid reaction

A case of amoebic liver abscess presenting as myeloid Leukemoid reaction in a forty year male is reported. The presenting white cell count was 144.8 x 10 / I and peripheral smear mimicked chronic myeloid leukemia - chronic phase. Treatment with metronidazole resulted in complete clinical and haematological cure. The recognition of the condition presenting as myeloid Leukemoid reaction is stressed in an endemic setting

Spontaneous rupture of the spleen

A 10 year old boy presented to the surgical service of the Queen Elizabeth Hospital with spontaneous rupture of the spleen and was later discovered to have chronic myeloid leukaemia. He has been in haematological remission for five years followed splenectomy and alpha-interferon therapy.