Pediatr Transplantation 2014: 18: 316–317
© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12234
Letter to the Editor Best treatment option for infantile chronic myeloid leukemia patients: Imatinib or hematopoietic stem cell transplantation? We were interested in the article by Alchalby and his colleagues about the hematopoietic stem cell transplantation (HSCT) and imatinib therapy in pediatric patients with chronic myeloid leukemia (CML). Philadelphia chromosome (Ph1)-positive CML is extremely rare in infants (1). That is why the treatment strategies for infantile CML remain controversial. Treatment with tyrosine kinase inhibitors (TKIs) has replaced HSCT in children especially without a matched sibling donor (MSD) (2). On the other hand, clinical observations in adult patients with CML yielded imatinib as front-line therapy (3). We disagree that this is true for children. The progression to accelerated phase under TKI therapy (4), potential long-term side effects (3) such as osteoporosis and pulmonary hypertension and also higher cost in developing countries (5) are major drawbacks. A 16-month-old girl presented with abdominal distension and anorexia lasting for a month. She had prominent hepatosplenomegaly. Complete blood count showed hemoglobin of 9.4 g/dL, platelet count of 349 9 109/L, and total leukocyte count of 229 9 109/L with a differential count of 17% promyelocyte, 10% myelocyte, 40% stab/ neutrophil, 11% eosinophil, 6% monocyte, 1% basophil, and 15% lymphocyte. Bone marrow aspirate showed no blasts. Leukocyte alkaline phosphatase score was five (range: 20–137), and fetal hemoglobin level was normal. Karyotypic study revealed Ph1 positivity (46, XX, t(9;22)(q34; q11). RT-PCR showed presence of both b3a3 and b2a2 variants of bcr-abl fusion gene. Imatinib was started at the dose of 340 mg/m2. Hematological response was achieved with imatinib therapy at one month. FISH analysis performed after three months showed bcr-abl variants fusion positive in 8.7% b3a3 and 7.4% b2a2 (partial response). After six months of therapy, RT-PCR showed presence of BCR/ABL positivity (0.1006%) (optimal response). She underwent 316
HSCT from matched unrelated donor (MUD) after seven months of imatinib. The patient experienced acute GvHD (grade II) and CMV infection, which were treated successfully. She was fully chimeric, and t(9;22) was negative after HSCT. Chronic GvHD (skin and liver) was detected on +195th day, and CMV pneumonia was diagnosed on +332nd day. She was intubated and admitted to the intensive care unit. But unfortunately, she died due to ARDS on +343th day. Just after the best therapeutic response with TKI in the chronic phase, HSCT with MSD/ MUD is the treatment of choice for children with CML (6, 7). But the high risk of morbidity and mortality even from MSDs should also be taken into account. It has been proposed that imatinib therapy would be more appropriate therapy for patients without MSD. Some authors recommend that allo-SCT in children should be postponed until the disease becomes refractory to imatinib (3). To the best of our knowledge, our patient was one of the youngest patients to undergo HSCT in the literature. Although she died of CMV pneumonia, which is one of the complications of HSCT, we still believe that the best curative option for pediatric/infantile CML patients is HSCT until novel drugs with less toxicity and higher efficacy are produced. Authors’ contributions All authors contributed to data acquisition and drafting the paper.
Arzu Akcay1, Deniz Tugcu1, Gonul Aydogan1, Fatih Erbey2, Zafer Salcioglu1, Ferhan Akici1and Gulyuz Ozturk2 1 Department of Pediatrics, Pediatric Hematology-Oncology, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey, 2Pediatric Bone Marrow Transplantation Unit, Bahcelievler Medical Park Hospital, Istanbul, Turkey E-mail: [email protected]
Letter to the Editor
References 1. MISHRA A, TRIPATHI K, MOHANTY L, PUJARI S. Philadelphia chromosome positive chronic myelogenous leukemia in a child: A case report. Indian J Hematol Blood Transfus 2010: 26: 109– 110. 2. SUTTORP M, MILLOT F. Treatment of pediatric chronic myeloid leukemia in the year 2010: Use of tyrosine kinase inhibitors and stem-cell transplantation. Hematology Am Soc Hematol Educ Program 2010: 2010: 368–376. 3. LEE JW, CHUNG NG. The treatment of pediatric chronic myelogenous leukemia in the imatinib era. Korean J Pediatr 2011: 54: 111–116.
4. HOCHHAUS A, SCHENK T, ERBEN P, et al. Cause and management of therapy resistance. Best Pract Res Clin Haematol 2009: 22: 367–379. 5. EL-ALFY MS, AL-HADDAD AM, HAMED AA. Management of CML in the pediatric age group: Imatinib mesylate or SCT. J Egypt Natl Canc Inst 2010: 22: 227–232. 6. APPERLEY J. CML in pregnancy and childhood. Best Pract Res Clin Haematol 2009: 22: 455–474. 7. GOLDMAN JM. How I treat CML in the imatinib era. Blood 2007: 110: 2828–2837.
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© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Pediatric Transplantation DOI: 10.1111/petr.12234
Letter to the Editor Best treatment option for infantile chronic myeloid leukemia patients: Imatinib or hematopoietic stem cell transplantation? We were interested in the article by Alchalby and his colleagues about the hematopoietic stem cell transplantation (HSCT) and imatinib therapy in pediatric patients with chronic myeloid leukemia (CML). Philadelphia chromosome (Ph1)-positive CML is extremely rare in infants (1). That is why the treatment strategies for infantile CML remain controversial. Treatment with tyrosine kinase inhibitors (TKIs) has replaced HSCT in children especially without a matched sibling donor (MSD) (2). On the other hand, clinical observations in adult patients with CML yielded imatinib as front-line therapy (3). We disagree that this is true for children. The progression to accelerated phase under TKI therapy (4), potential long-term side effects (3) such as osteoporosis and pulmonary hypertension and also higher cost in developing countries (5) are major drawbacks. A 16-month-old girl presented with abdominal distension and anorexia lasting for a month. She had prominent hepatosplenomegaly. Complete blood count showed hemoglobin of 9.4 g/dL, platelet count of 349 9 109/L, and total leukocyte count of 229 9 109/L with a differential count of 17% promyelocyte, 10% myelocyte, 40% stab/ neutrophil, 11% eosinophil, 6% monocyte, 1% basophil, and 15% lymphocyte. Bone marrow aspirate showed no blasts. Leukocyte alkaline phosphatase score was five (range: 20–137), and fetal hemoglobin level was normal. Karyotypic study revealed Ph1 positivity (46, XX, t(9;22)(q34; q11). RT-PCR showed presence of both b3a3 and b2a2 variants of bcr-abl fusion gene. Imatinib was started at the dose of 340 mg/m2. Hematological response was achieved with imatinib therapy at one month. FISH analysis performed after three months showed bcr-abl variants fusion positive in 8.7% b3a3 and 7.4% b2a2 (partial response). After six months of therapy, RT-PCR showed presence of BCR/ABL positivity (0.1006%) (optimal response). She underwent 316
HSCT from matched unrelated donor (MUD) after seven months of imatinib. The patient experienced acute GvHD (grade II) and CMV infection, which were treated successfully. She was fully chimeric, and t(9;22) was negative after HSCT. Chronic GvHD (skin and liver) was detected on +195th day, and CMV pneumonia was diagnosed on +332nd day. She was intubated and admitted to the intensive care unit. But unfortunately, she died due to ARDS on +343th day. Just after the best therapeutic response with TKI in the chronic phase, HSCT with MSD/ MUD is the treatment of choice for children with CML (6, 7). But the high risk of morbidity and mortality even from MSDs should also be taken into account. It has been proposed that imatinib therapy would be more appropriate therapy for patients without MSD. Some authors recommend that allo-SCT in children should be postponed until the disease becomes refractory to imatinib (3). To the best of our knowledge, our patient was one of the youngest patients to undergo HSCT in the literature. Although she died of CMV pneumonia, which is one of the complications of HSCT, we still believe that the best curative option for pediatric/infantile CML patients is HSCT until novel drugs with less toxicity and higher efficacy are produced. Authors’ contributions All authors contributed to data acquisition and drafting the paper.
Arzu Akcay1, Deniz Tugcu1, Gonul Aydogan1, Fatih Erbey2, Zafer Salcioglu1, Ferhan Akici1and Gulyuz Ozturk2 1 Department of Pediatrics, Pediatric Hematology-Oncology, Istanbul Kanuni Sultan Suleyman Training and Research Hospital, Istanbul, Turkey, 2Pediatric Bone Marrow Transplantation Unit, Bahcelievler Medical Park Hospital, Istanbul, Turkey E-mail: [email protected]
Letter to the Editor
References 1. MISHRA A, TRIPATHI K, MOHANTY L, PUJARI S. Philadelphia chromosome positive chronic myelogenous leukemia in a child: A case report. Indian J Hematol Blood Transfus 2010: 26: 109– 110. 2. SUTTORP M, MILLOT F. Treatment of pediatric chronic myeloid leukemia in the year 2010: Use of tyrosine kinase inhibitors and stem-cell transplantation. Hematology Am Soc Hematol Educ Program 2010: 2010: 368–376. 3. LEE JW, CHUNG NG. The treatment of pediatric chronic myelogenous leukemia in the imatinib era. Korean J Pediatr 2011: 54: 111–116.
4. HOCHHAUS A, SCHENK T, ERBEN P, et al. Cause and management of therapy resistance. Best Pract Res Clin Haematol 2009: 22: 367–379. 5. EL-ALFY MS, AL-HADDAD AM, HAMED AA. Management of CML in the pediatric age group: Imatinib mesylate or SCT. J Egypt Natl Canc Inst 2010: 22: 227–232. 6. APPERLEY J. CML in pregnancy and childhood. Best Pract Res Clin Haematol 2009: 22: 455–474. 7. GOLDMAN JM. How I treat CML in the imatinib era. Blood 2007: 110: 2828–2837.
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