scholarly journals Successful treatment of pulmonary tuberculosis in a child with acute promyelocytic leukemia, on the background of intensive chemotherapy

2021 ◽  
pp. 44-54
Author(s):  
O.I. Dorosh ◽  
◽  
Yu.O. Letz ◽  
I.P. Melko ◽  
I.P. Tsymbalyuk-Voloshin ◽  
...  
Keyword(s):  
Pulmonary Tuberculosis ◽  
Acute Leukemia ◽  
Acute Promyelocytic Leukemia ◽  
Molecular Genetic ◽  
Infectious Complications ◽  
Promyelocytic Leukemia ◽  
Cytostatic Therapy ◽  
Molecular Genetic Study ◽  
Hematopoietic Stem ◽  
Tb Treatment

The predisposition of patients with acute leukemia (АL) to various infectious complications is a well-known fact. The reason is a decrease in immunity due to the underlying disease and due to the use of immunosuppressive cytostatic and radiotherapy. Tuberculosis infections (TIs) are serious and life-threatening complications in patients with malignant hematological disorders and recipients after hematopoietic stem cell transplantation. Verification of tuberculosis (TB) is often delayed among patients with hematooncological diseases due to low suspicion and due to the search for other infectious complications. Those with the involvement of the respiratory system are the most common complications in immunologically compromised patients. In acute leukemia, the TB process may have been underestimated, due to negative tests for mycobacterium tuberculosis (MBT), and patients with neoplasia are often prescribed antibacterial agents such as amikacin and ftorchinolones, which are also effective against TI. We describe a 10-year-old boy who was diagnosed with pulmonary tuberculosis, a disseminated form complicated by hydrothorax, during induction chemotherapy for acute promyelocytic leukemia (APL). For diagnostic purposes, repeated punctures of the pleural cavity with drainage of pathological effusion and diagnostic and remedial bronchoscopy were performed, bacterial pneumonia and systemic mycosis were suspected. The diagnosis of TB was verified on the basis of positive PCR test for TB, molecular genetic study of sputum, bronchial lavage for the presence of genome of MBT without resistance to rifampicin, sputum microscopy, while sputum culture and pleural fluid were negative for MBT. TB treatment was coEadministered with AML-BFM 2004 intensive cytostatic therapy without dose reduction of cytostatics. The child was prescribed intensive tuberculostatic therapy with 4 drugs (rifampicin + isoniazid + pyrazinamide + inbutol) for 3 months and subsequent maintenance antituberculous chemotherapy with two drugs for 4 months (rifampicin + isonimazide). With this analysis, we advocate the need for early suspicion of TB in patients receiving treatment for AL. The results of our study suggest that antitumor chemotherapy is not an obstacle to effective TB-treatment. The described patient is in remission of AML and TB for 21 months. The research was carried out in accordance with the principles of the Helsinki declaration. The informed consent of the patient was obtained for conducting the studies. No conflict of interest was declared by the authors. Key words: acute promyelocytic leukemia, tuberculosis, cytostatic therapy, children.

Treatment of Relapsed Acute Promyelocytic Leukemia by Arsenic-Based Strategies without Hematopoietic Stem Cell Transplantation in Hong Kong: A Seven-Year Experience.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 395-395 ◽  
Author(s):  
Wing Y. Au ◽  
James C. Chim ◽  
Albert K. Lie ◽  
Cyrus R. Kumana ◽  
Anskar Y. Leung ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Promyelocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Promyelocytic Leukemia ◽  
High Morbidity ◽  
Hematopoietic Stem

Abstract Background: The optimal therapy for relapsed acute promyelocytic leukemia (APL) after arsenic trioxide (As2O3)-induced remission is unclear. Hematopoietic stem cell transplantation (HSCT) is associated with high morbidity and mortality. Moreover, lasting remission is observed in many patients who are not candidates for HSCT, owing to advanced age or lack of donors, implying that HSCT is not mandatory for durable remission. We evaluated our results of an As2O3-based, non-HSCT regimen for patients with relapsed APL. Materials and methods: Forty-two consecutive patients (18 men, 24 women, median age: 35 years, 12–72) with relapsed (relapse 1, R1=39, R2=3) APL were treated with an-As2O3 based, non-HSCT regimen. The time from last complete remission (CR) was 22 (6–243) months (mo). Initial treatment was As2O3 (10 mg/day) either intravenously (n=16) or orally (n=28) until CR, followed by idarubicin consolidation (6 mg/m2/day x 9). Twenty-five patients received oral-As2O3 maintenance. Post-As2O3 relapses were treated with oral As2O3 + all-trans retinoic acid (ATRA, 45 mg/m2/day) until CR, followed by maintenance (two weeks of ATRA+As2O3 every 2 mo. for 2 years). Post-As2O3/ATRA relapses were treated with oral As2O3+ATRA+ascorbic acid (1g/day) until CR, followed by consolidation/maintenance with the same regimen (2 weeks every 2 mo. for 2 years). Part of the induction and all of the maintenance therapies were given in the outpatient clinic. Results: Forty-one patients (98%) achieved CR after initial As2O3 treatment. One 72-year old man with XYY syndrome, diabetes and mental retardation died of pneumonia. Thirteen relapses occurred at a median of 15 (6–22) mo. As2O3-maintenance significantly decreased further relapses (3/24 with versus 10/17 without As2O3-maintenance, p=0.003). Two relapses died of cerebral APL before further treatment could be administered. Of eleven patients treated with As2O3+ATRA, 10 achieved CR, 8 of whom have remained in remission (median follow-up: 33 mo.). Two post-As2O3/ATRA relapses achieved CR again with As2O3+ATRA+ascorbic acid, and have remained in remission after maintenance treatment with As2O3+ATRA+ascorbic acid. All patients in continuous remission (n=38) were PML/RARa negative on polymerase chain reaction (sensitivity 10−3 to 10−4). Conclusion: Our regimen resulted in a leukemia-free-survival of 89.3%. The results suggest that an oral and mainly outpatient As2O3-based, non-HSCT strategy is efficacious for relapsed APL. In terms of survival, costs, treatment side effects and patient tolerance, the results appear to be comparable to, if not more favorable than, other treatment options based on high dose chemotherapy, graft-versus-leukemia effect, or anti-myeloid antibody therapy.

A Risk Model for Early Intracranial Hemorrhage in Acute Leukemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4473-4473
Author(s):  
Hawk Kim ◽  
Seong-Jun Choi ◽  
Je-Hwan Lee ◽  
Jung-Shin Lee ◽  
Kyoo Hyung Lee
Keyword(s):  
Acute Leukemia ◽  
Prothrombin Time ◽  
Acute Promyelocytic Leukemia ◽  
Induction Chemotherapy ◽  
Intracranial Hemorrhage ◽  
Risk Model ◽  
Female Gender ◽  
Promyelocytic Leukemia ◽  
Free Survival ◽  
Prolonged Prothrombin Time

Abstract Early intracranial hemorrhage (EICH), which is defined by noticeable ICH within 10 days of diagnosis, is a life-threatening hemorrhagic complication in patients with acute leukemia. To ascertain risk factors associated with EICH, we retrospectively analyzed 792 newly-diagnosed acute leukemia patients treated between July 1988 and March 2003. Thirty-one patients (3.9 %) had analyzable EICH. Multivariate analysis showed that female gender (OR = 3.064, P < 0.001), acute promyelocytic leukemia (OR = 8.797, P = 0.003), leukocytosis (OR = 6.056, P = 0.004), and prolonged prothrombin time (OR = 10.026, P = 0.016) were factors significantly associated with occurrence of EICH. Risk scores (RS) were calculated by a product of odds ratio and each risk factor (RF) and taking their sum, generating an RS ranging 0 to 27.943. The cutoff of RS 9 was of statistical significance to predict probability of EICH. Receiver-operating characteristics curve shows the sensitivity and 1 - specificity relative to risk score (AUC = 0.917; S.E. = 0.021; 95% CI, 0.876–0.958; Figure 1). In this regards, RF for EICH was classified as major (prolonged prothrombin time) and minor (female gender, acute promyelocytic leukemia, leukocytosis). Risk model demonstrated that EICH was low probable when no major RF and less than two minor RFs were present. Risk model for ICH in acute leukemia classified acute leukemia patients into two risk groups; low probable EICH group (LPG) and probable EICH group (PG). When applied to our patients, PG was positively correlated with more incidence of FICH than LPG (n = 27/173 vs. 4/619, P < 0.001). Induction chemotherapy could be undertook more frequently in LPG than in PG (p = 0.002, Table 1). Kaplan-Meier curves show the probability of EICH-free survival relative to probability of EICH. ICH-free survival was significantly longer in LPG than in PG (p < 0.0001, Figure 2). Our findings suggest that our risk model may predict the occurrence of EICH in patients with acute leukemia. Table 1. The relationship of risk model and frequency of early intracranial hemorrhage (EICH) or performance of induction chemotherapy. Figure Figure Figure Figure Low probable EICH group, n (%) Probable EICH group, n (%) P EICH (−) 615 (77.7 %) 146 (18.4 %) < 0.001 EICH (+) 4 (0.5 %) 27 (3.4 %) Induction chemotherapy (+) 563 (71.1 %) 143 (18.1 %) 0.002 Induction chemotherapy (−) 56 (7.1 %) 30 (3.8 %)

Treatment of Relapsed Acute Promyelocytic Leukemia with Oral Arsenic Trioxide: An Eleven-Year Experience

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2958-2958
Author(s):  
Wing-Yan Au ◽  
Sidney Tam ◽  
Anskar Y.H. Leung ◽  
Eric Tse ◽  
Cyrus Kumana ◽  
...  
Keyword(s):  
Ascorbic Acid ◽  
Arsenic Trioxide ◽  
Acute Promyelocytic Leukemia ◽  
Maintenance Treatment ◽  
Histone Deacetylase Inhibitors ◽  
Significant Proportion ◽  
Gemtuzumab Ozogamicin ◽  
Promyelocytic Leukemia ◽  
Hematopoietic Stem

Abstract Background. For patients with relapsed acute promyelocytic leukemia (APL), the optimal therapy after arsenic trioxide (As2O3)-induced complete remission (CR) is unclear. Autologous or allogeneic hematopoietic stem cell transplantation (HSCT) has been advocated. These strategies are associated with morbidity and considerable mortality, and not all patients are eligible. The role of maintenance therapy with As2O3 remains undefined. Materials and methods. From 1997–2008, 50 consecutive APL patients (25 men, 25 women, median age: 35 (12–72) years) in relapse (R1, n=47; R2, n=3) were treated with As2O3 until CR. This was followed by idarubicin consolidation (6 mg/m2/day × 9) in 43 patients. Seventeen patients did not receive maintenance treatment. Thirty-two patients received oral-As2O3 maintenance (10 mg/day × 14 every 2 months). All-trans retinoic acid (ATRA, 45 mg/m2/day) maintenance was used together with oral-As2O3 in 27 patients. As2O3 protocol was approved by the institutional review board at Queen Mary Hospital. All maintenance treatment was given in the outpatient clinic as oral medication. Results. Of 50 relapsed cases, As2O3-induced CR was achieved in 49 patients, 1 patient dying of pneumonia. At a median follow-up of 61 (6–122) months, 27 patients (19 with and 8 without As2O3 maintenance) had remained in remission. Further relapses (R2, n=20; R3, n=2.) occurred in 22 patients (13 with and 9 without As2O3 maintenance), at a median of 16 (6–28) months. Concomitant central nervous system (CNS) relapse occurred in 8 cases. Treatment of post-As2O3 relapses included oral-As2O3 (10 mg/day) + ATRA (45 mg/m2/day) with (n=10) or without (n=10) ascorbic acid (1 gm/day) until CR, and then maintenance with As2O3 + ATRA +/− ascorbic acid. Leucocytosis during treatment was controlled with mitoxantrone. In these 22 cases of post-As2O3 relapses, further remission was still achieved in 19 patients (CR3, n=18; CR4, n=1), with 3 patients dying from cerebral bleeding. At a median follow-up of 88 (8–98) months, 8 patients had remained in remission. Further relapses occurred in 11 patients. Salvage therapy consisted of As2O3+ATRA+ascorbic acid, together with chemotherapy (mitoxantrone, n=8; amascrine, n=3), gemtuzumab ozogamicin (n=4), and autologous HSCT (n=1). Eight patients finally died of refractory leukemia after a median of 6 (2–33) months. Three patients had remained in remission (CR4, n=2, CR5 n=1) at a median of 41 (26–102) months. On an intention-totreat basis, our oral-As2O3 treatment/maintenance regimen for patients with relapsed APL resulted in a 4-year overall survival of 71%, and event-free-survival of 53%. Conclusion. Our findings showed that an oral-As2O3-based treatment/maintenance strategy resulted in durable remission in a significant proportion of patients with relapsed APL. As most of the treatment is administered at home, this regimen involves much less financial, personnel and emotional costs as compared with HSCT strategies. Further improvement should be directed towards prevention of CNS relapses with appropriate prophylaxis in high-risk patients. For remissions at or beyond CR3, consideration of HSC harvest and storage at molecular remission should be considered. The use of demethylation agents and histone deacetylase inhibitors in combination with As2O3 remains to be investigated.

Iron Metabolism before Allo-HSCT in Patients with Acute Leukemia and Impact of Iron Overload on Transplantation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2461-2461
Author(s):  
Jimin Shi ◽  
Xuying Pei ◽  
Yi Luo ◽  
Yamin Tan ◽  
Yanmin Zhao ◽  
...  
Keyword(s):  
Acute Leukemia ◽  
Iron Overload ◽  
Iron Metabolism ◽  
Bacterial Infections ◽  
Conflicts Of Interest ◽  
Infectious Complications ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Hematopoietic Stem ◽  
Increased Risk

Abstract Objective: Iron overload is common in patients with acute leukemia who undergoing allogenic hematopoietic stem cell transplantation (allo-HSCT). We performed a comprehensive analysis of iron parameters to assess these patients' iron metabolism, and studied the prognostic impact of pretransplant iron overload on the outcome of transplantation. Methods: In this retrospective study, we studied 124 patients undergoing myeloablative allo-HSCT between 2012 and 2014. Serum iron (SI), serum ferritin (SF), hepcidin (Hepc) and soluble transferrin receptor (sTfR) were measured before transplant. We analyzed the effect of elevated pretransplant ferritin on acute graft versus host disease (aGVHD), infectious complications, overall survival (OS) and non-relapse mortality (NRM). Results: Date of 124 patients (including 56 cases of acute lymphocytic leukemia and 68 cases of acute myeloid leukemia) were analyzed. Median SI, SF, Hepc and sTfR values were 12.15 umol/L, 667.05 ng/ml, 369.50 ng/L and 7.69 ng/ml, respectively. Iron overload (defined as SF>1000 ng/ml) were observed in 27.42% of patients. Pretransplant iron overload was significantly associated with increased risk of bacterial infections during the early post-transplant period, and with reduced risk of aGVHD. Pretransplant iron overload increased NRM and reduced OS, but there were no significant differences. Conclusion: Patients with acute leukemia regularly develop iron overload before they undergoing allo-HSCT. Pretransplant iron overload was correlated with transplantation outcome. Disclosures No relevant conflicts of interest to declare.

scholarly journals How I treat hematologic emergencies in adults with acute leukemia

Blood ◽  
2012 ◽  
Vol 120 (10) ◽  
pp. 1993-2002 ◽  
Author(s):  
Tsila Zuckerman ◽  
Chezi Ganzel ◽  
Martin S. Tallman ◽  
Jacob M. Rowe
Keyword(s):  
Acute Leukemia ◽  
Acute Promyelocytic Leukemia ◽  
Lymphoblastic Leukemia ◽  
Practical Experience ◽  
Promyelocytic Leukemia ◽  
Neutropenic Enterocolitis ◽  
Formidable Challenge ◽  
Prospective Trials ◽  
Long Term Survivors

Abstract Acute myeloid leukemia and acute lymphoblastic leukemia remain devastating diseases. Only approximately 40% of younger and 10% of older adults are long-term survivors. Although curing the leukemia is always the most formidable challenge, complications from the disease itself and its treatment are associated with significant morbidity and mortality. Such complications, discussed herein, include tumor lysis, hyperleukocytosis, cytarabine-induced cellebellar toxicity, acute promyelocytic leukemia differentiation syndrome, thrombohemorrhagic syndrome in acute promyelocytic leukemia, L-asparaginase-associated thrombosis, leukemic meningitis, neutropenic fever, neutropenic enterocolitis, and transfussion-associated GVHD. Whereas clinical trials form the backbone for the management of acute leukemia, emergent clinical situations, predictable or not, are common and do not readily lend themselves to clinical trial evaluation. Furthermore, practice guidelines are often lacking. Not only are prospective trials impractical because of the emergent nature of the issue at hand, but clinicians are often reluctant to randomize such patients. Extensive practical experience is crucial and, even if there is no consensus, management of such emergencies should be guided by an understanding of the underlying pathophysiologic mechanisms.

scholarly journals Hyperbasophilic Variant of Acute Promyelocytic Leukemia

2016 ◽  
Vol 3 (2) ◽  
pp. 125
Author(s):  
Preeti Bajaj ◽  
Rajyaguru Devangana ◽  
B. S. Shah ◽  
Amrinder Kaur
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Promyelocytic Leukemia ◽  
Myeloid Leukemia ◽  
Molecular Genetic ◽  
Chromosomal Translocation ◽  
Promyelocytic Leukemia ◽  
Chromosome 17 ◽  
Chromosome 15 ◽  
Chromosome 11 ◽  
Acute Myeloid

Acute Promyelocytic Leukemia (APL) is an extremely rare variant of acute myeloid leukemia. APL constitutes around 10-15 % of acute myeloid leukemia in adults. It is commonly diagnosed around 40 years age. Molecular/genetic studies exhibit chromosomal translocation between chromosome 15 and chromosome 17-t(15;17)(q22;q21) and PML-RARa rearrangement. Four variants of APL have been identified: The classic form M<sub>3</sub> hypergranular variant, the microgranular variant, the hyperbasophilic form and zinc-finger form-M<sub>3</sub>r, identified by a different chromosomal translocation, between chromosome 11 and chromosome 17:t(11,17) (q23, q11-12).

scholarly journals Role of Hematopoietic Stem Cell Transplantation in Acute Promyelocytic Leukemia

2021 ◽  
Vol 11 ◽  
Author(s):  
Jaime Sanz ◽  
Pau Montesinos ◽  
Miguel A. Sanz
Keyword(s):  
Stem Cell ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Acute Promyelocytic Leukemia ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Promyelocytic Leukemia ◽  
Controlled Study ◽  
High Dose ◽  
Hematopoietic Stem

The indication of hematopoietic stem cell transplantation (HSCT) in acute promyelocytic leukemia (APL) has evolved historically from a widespread use in front-line therapy during the pre-ATRA era to a virtual rejection of this indication for patients treated with modern treatments. HSCT in first complete remission could only be considered for an extremely small fraction of patients with persistent MRD at the end of consolidation or for those who relapse. In the pre-ATO era, relapsed patients were usually treated with readministration of ATRA and chemotherapy as salvage therapy, generally containing high-dose cytarabine and an anthracycline, followed by further post-remission chemotherapy and/or HSCT. ATO-based regimens are presently regarded as the first option for relapsed APL. The selection of the most appropriate post-remission treatment option for patients in second CR (CR2), as well as the modality of HSCT when indicated, depends on several variables, such as pre-transplant molecular status, duration of first remission, age, and donor availability. Although with a moderate level of evidence, based on recent retrospective studies, autologous HSCT would be at present the preferred option for consolidation for patients in molecular CR2. Allogeneic HSCT could be considered in patients with a very early relapse or those beyond CR2. Nevertheless, the superiority of HSCT as consolidation over other alternatives without transplantation has recently been questioned in some studies, which justify a prospective controlled study to resolve this still controversial issue.

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