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Current therapy for chronic granulomatous disease
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2. 3.
4.
Editorial correspondence
Rowley AH, Shulman ST. The search for the etiology of Kawasak! disease. Pediatr Infect Dis J 1987;6:506-8. Newburger JN, Takahashi M, Burns JG, et al. The treatment of Kawasaki syndrome with intravenous gammaglobulin. N Engl J Med 1986;315:341-7. Rowley AH, Dully CE, Shulman ST. Prevention of giant coronary artery aneurysms in Kawasaki disease by intravenous gamma globulin therapy. J PEDtATR 1988il 13:290-4.
The Journal of Pediatrics June 1989
2.
linked variant chronic granulomatous disease. J Clin Invest 1987;80:1009-16. Ezekowitz RAB, Dinauer MC, Jaffe HS, Orkin SH, Newburger pE. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma, N Engl J Med 1988; 319:146-51.
Reply To the Editor:
Current therapy for chronic
granulomatous disease To the Editor: Bone marrow transplantation (BMT) is used in the treatment of diseases of the hematopoietic system such as chronic granulomatous disease (CGD). The report by Kamani et al. (J. PEDIATR 1988:113:697-700) described a patient with CGD who had been infection free for 6 years after an allogeneic BMT. This patient has low level but stable hematopoietic chimerism resulting in 10% to 23% of peripheral neutrophils of donor origin. The authors discussed the risks and benefits of BMT for CGD and recommended that if a BMT is being considered, it should be done "'early in life before the appearance of severe infections or irreversible tissue damage." Recently, interferon gamma has been shown to activate normal neutrophils by causing increased production of cytochrome b heavy chain 5- to 15-fold? The neutrophils of several patients with CGD also responded in vitro and in vivo with increased bactericidal activity. 2 This "pharmacologic modulation of gene expression in human d i s e a s e . . , suggest a potential role for interferon gamma in the prophylaxis of infections or as an adjunct to conventional antimicrobial therapy for acute infections in patients with chronic granulomatous disease.''2 In light of these new findings, patients with CGD, especially those who are presently being considered for BMT. should be entered into clinical trials to receive interferon gamma to determine whether there is any increase in phagocytic function in vitro and in vivo and to see whether this correlates with increased resistance to infection. CGD patients with low levels of baseline activity of cytochrome b will probably respond favorably to interferon gamma. Patients who have CGD because of gene deletion or other mutation that totally !nactivates all cytochrome b function may not respond to interferon gamma. These are the patients who will be the most likely candidates for BMT now and direct gene therapy in the future.
Louie Naumovski, MD, PhD Stephen D. Smith, MD Department of Pediatrics Division of Hematology/Oncology Children's Hospital at Stanford Palo Alto, CA 94304
We concur with Drs. Naumovski and Smith in their contention that some patients with chronic granul0matous disease (CGD) may benefit from therapies other than bone marrow transplantation. In any disease in which two or more therapies may be expected to benefit patients, one should consider all the risks and benefits of each treatment and use the safer one. With regard to the potential role of interferon gamma in the treatment of CGD, several issues should be analyzed. Ezekowitz et al. 1 showed that four patients with X-linked CGD treated with two subcutaneous injections of 0.1 mg/m2/dose recombinant interferon gamma given on consecutive days showed complete or partial correction of their phagocyte defect. In the most responsive patients, the restoration of function persisted for several weeks. We are aware that longer-term clinical trials with larger numbers of patients are now under way to evaluate further the role of interferon gamma in CGD. Ault et al. 2 recently reported the occurrence of a lifethreatening complication of acute renal failure during therapy with recombinant interferon gamma in a patient with acute leukemia. The role of interferon gamma in CGD cannot be properly evaluated until we have studies demonstrating its longterm efficacy and safety. Despite its multiple complications, allogeneic marrow transplantation is at present the only potentially curative therapeutic modality available for these patients.
Naynesh Kamani, MD Steven D. Douglas, MD Charles S. August, MD Division of Allergy/Immunology/BMT Children's Hospital of Philadelphia Philadelphia, PA 19104 REFERENCES
1. Ezek0witz RAB, Dinauer MC, Jaffe HS, Orkin SH, Newburger PE. Partia~ correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med 1988; 319:146-51. 2. Ault BH, Stapleton FB, Gaber L, Martin A, Roy S, Murphy SB. Acute renal failure during therapy with recombinant human gamma interferon. N Engl J Med 1988;319:1397400.
Cow milk protein as a cause of infantile colic
REFERENCES
1.
Ezekowitz RAB, Orkin SH, Newburger PE. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous gene expression in X-
To The Editor: The report by Moore et al. (J PEDIATR 1988;113:979-84) shows a relationship between the clinical signs of colic and colonic gas
2. 3.
4.
Editorial correspondence
Rowley AH, Shulman ST. The search for the etiology of Kawasak! disease. Pediatr Infect Dis J 1987;6:506-8. Newburger JN, Takahashi M, Burns JG, et al. The treatment of Kawasaki syndrome with intravenous gammaglobulin. N Engl J Med 1986;315:341-7. Rowley AH, Dully CE, Shulman ST. Prevention of giant coronary artery aneurysms in Kawasaki disease by intravenous gamma globulin therapy. J PEDtATR 1988il 13:290-4.
The Journal of Pediatrics June 1989
2.
linked variant chronic granulomatous disease. J Clin Invest 1987;80:1009-16. Ezekowitz RAB, Dinauer MC, Jaffe HS, Orkin SH, Newburger pE. Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma, N Engl J Med 1988; 319:146-51.
Reply To the Editor:
Current therapy for chronic
granulomatous disease To the Editor: Bone marrow transplantation (BMT) is used in the treatment of diseases of the hematopoietic system such as chronic granulomatous disease (CGD). The report by Kamani et al. (J. PEDIATR 1988:113:697-700) described a patient with CGD who had been infection free for 6 years after an allogeneic BMT. This patient has low level but stable hematopoietic chimerism resulting in 10% to 23% of peripheral neutrophils of donor origin. The authors discussed the risks and benefits of BMT for CGD and recommended that if a BMT is being considered, it should be done "'early in life before the appearance of severe infections or irreversible tissue damage." Recently, interferon gamma has been shown to activate normal neutrophils by causing increased production of cytochrome b heavy chain 5- to 15-fold? The neutrophils of several patients with CGD also responded in vitro and in vivo with increased bactericidal activity. 2 This "pharmacologic modulation of gene expression in human d i s e a s e . . , suggest a potential role for interferon gamma in the prophylaxis of infections or as an adjunct to conventional antimicrobial therapy for acute infections in patients with chronic granulomatous disease.''2 In light of these new findings, patients with CGD, especially those who are presently being considered for BMT. should be entered into clinical trials to receive interferon gamma to determine whether there is any increase in phagocytic function in vitro and in vivo and to see whether this correlates with increased resistance to infection. CGD patients with low levels of baseline activity of cytochrome b will probably respond favorably to interferon gamma. Patients who have CGD because of gene deletion or other mutation that totally !nactivates all cytochrome b function may not respond to interferon gamma. These are the patients who will be the most likely candidates for BMT now and direct gene therapy in the future.
Louie Naumovski, MD, PhD Stephen D. Smith, MD Department of Pediatrics Division of Hematology/Oncology Children's Hospital at Stanford Palo Alto, CA 94304
We concur with Drs. Naumovski and Smith in their contention that some patients with chronic granul0matous disease (CGD) may benefit from therapies other than bone marrow transplantation. In any disease in which two or more therapies may be expected to benefit patients, one should consider all the risks and benefits of each treatment and use the safer one. With regard to the potential role of interferon gamma in the treatment of CGD, several issues should be analyzed. Ezekowitz et al. 1 showed that four patients with X-linked CGD treated with two subcutaneous injections of 0.1 mg/m2/dose recombinant interferon gamma given on consecutive days showed complete or partial correction of their phagocyte defect. In the most responsive patients, the restoration of function persisted for several weeks. We are aware that longer-term clinical trials with larger numbers of patients are now under way to evaluate further the role of interferon gamma in CGD. Ault et al. 2 recently reported the occurrence of a lifethreatening complication of acute renal failure during therapy with recombinant interferon gamma in a patient with acute leukemia. The role of interferon gamma in CGD cannot be properly evaluated until we have studies demonstrating its longterm efficacy and safety. Despite its multiple complications, allogeneic marrow transplantation is at present the only potentially curative therapeutic modality available for these patients.
Naynesh Kamani, MD Steven D. Douglas, MD Charles S. August, MD Division of Allergy/Immunology/BMT Children's Hospital of Philadelphia Philadelphia, PA 19104 REFERENCES
1. Ezek0witz RAB, Dinauer MC, Jaffe HS, Orkin SH, Newburger PE. Partia~ correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med 1988; 319:146-51. 2. Ault BH, Stapleton FB, Gaber L, Martin A, Roy S, Murphy SB. Acute renal failure during therapy with recombinant human gamma interferon. N Engl J Med 1988;319:1397400.
Cow milk protein as a cause of infantile colic
REFERENCES
1.
Ezekowitz RAB, Orkin SH, Newburger PE. Recombinant interferon gamma augments phagocyte superoxide production and X-chronic granulomatous gene expression in X-
To The Editor: The report by Moore et al. (J PEDIATR 1988;113:979-84) shows a relationship between the clinical signs of colic and colonic gas