Necrotizing Fasciitis in Two Children Acute Lymphoblastic Leukemia By Brian W. Duncan,
N. Scott Adzick,
Alfred
A. delorimier,
Michael
Seymour
Zoger,
and Michael
R. Harrison
With
T. Longaker,
Linda D. Ferrell,
San Francisco, California l Necrotizing fasciitis is a severe, soft tissue infection, and is an unusual condition in children. The cornerstone of therapy is prompt, aggressive surgical treatment. Despite vigorous treatment, mortality rates are high. We report the occurrence of necrotizing fasciitis in two children during the granulocytopenic phase of induction chemotherapy for acute lymphoblastic leukemia. The diagnosis and treatment of necrotizing fasciitis in these two children was made more difficult by their underlying disease and its chemotherapy. The successful treatment of their infections relied on a multimodality approach. Aggressive surgical debridement was the mainstay of therapy. Adjuvant therapy was vital to the successful outcomes and included meticulous wound care, intravenous hyperalimentation, appropriate antibiotics, and granulocyte transfusions. Copyright D 1992 by W.B. Saunders Company INDEX WORDS: leukemia.
Necrotizing
fasciitis;
acute lymphoblastic
N
ECROTIZING fasciitis is an uncommon, severe soft tissue infection characterized by necrosis of subcutaneous fat and fascia. The process is usually accompanied by severe systemic toxicity and high mortality rates.1-4 Necrotizing fasciitis is a rare entity in children. In the past year we have encountered two cases of necrotizing fasciitis in children with null cell acute lymphoblastic leukemia (ALL). Both of these children were profoundly neutropenic during the induction phase of chemotherapy. The diagnosis and treatment of this condition were made much more difficult by the underlying disease and chemotherapy. The eventual successful outcome was due to a multimodality approach utilizing aggressive surgical debridement and wound care as the cornerstone of therapy. CASE
REPORTS
Case 1 A 3-year-old white girl presented with recent onset of easy bruising, epistaxis, and hepatosplenomegally. Complete blood count showed 150,000 white blood cells with 95% blast forms. Bone
From the Department of Pediatric Surgery, University of California, San Francisco, San Francisco, CA. Address reprint requests to Michael R. Ham’son, MD, University of California, San Francisco, 3rd and Pamassus Aves, 585HSE, San Francisco, CA 94143. Copyright o 1992 by W.B. Saunders Company 0022-34681921270%0036$03.00/0
668
marrow aspirate and biopsy were consistent with null cell ALL. Induction chemotherapy was begun with vincristine, L-asparaginase, prednisone, daunomycin, and intrathecal methotrexate. On the 16th day of chemotherapy, a rash was noted on the patient’s left labium with extension to the buttocks. The child was lethargic and anorexic and complained of severe vaginal pain. The child was afebrile at that point. Topical Nystatin was administered for a presumed monilial rash. The patient’s absolute granulocyte count at that time was zero. Two days later, the first slight temperature elevation (382°C) developed. Left labial swelling and exquisite tenderness of the area were now noted. Broad-spectrum antibiotics were begun and the child underwent incision and drainage of the left labium. Thin serosanguinous fluid was expressed from the wound. Culture of this material and blood cultures obtained at that time grew Pseudomonas aeruginosa. Anaerobic cultures were negative. Three days later, there was rapid progression of the child’s perineal lesion with obvious cutaneous gangrene of the area (Fig 1). Erythematous. mottled, edematous changes of the skin extending to the abdominal wall and left thigh were now present. Emergency debridement was performed with extensive fasciotomies of the abdominal wall and left thigh (Fig 2). A left labial resection, diverting colostomy and vesicostomy were also performed. Pathological specimens showed widespread necrosis at the fascial level compatible with necrotizing fasciitis (Fig 3). Broad-spectrum antibiotics were continued throughout this period. Granulocyte transfusions, intravenous gamma globulin, and intravenous hyperalimentation were also given. Three subsequent debridements were necessary to completely remove affected tissue. The abdominal and thigh wounds were eventually closed primarily, and a split thickness skin graft was performed to close the labial wound (Fig 4). The child has subsequently had her colostomy and vesicostomy taken down. She recovered fully after a protracted course and remains in hematologic remission 2 years after her initial diagnosis of ALL, off of all medications.
Case 2 An 18-month-old white girl was admitted with a l-month history of an upper respiratory tract infection, lethargy, and easy bruising. Complete blood count had 44,000 white blood cells with 100% lymph forms. Bone marrow aspirate and biopsy demonstrated a null cell ALL. The patient was started on induction chemotherapy with the same regimen as case 1. The patient undetwent a repeat right iliac crest bone marrow biopsy on the 14th day of chemotherapy that demonstrated a hypocellular marrow without evidence of leukemia. The patient’s absolute granulocyte count at the time was zero. Four days later, a small area of cellulitis was noted at the biopsy site. The child was afebrile at that time. Incision and drainage with biopsy of this site were performed. Both blood and tissue cultures subsequently grew a multiply resistant E coli. Anaerobic cultures were negative. The cellulitis at the biopsy site remained unchanged until 4 days later when progressive erythema and edema over an extensive area of the child’s sacral region were noted. Surgical exploration showed
JournalofPediafric Surgery, Vol 27, No 5 (May), 1992: pp 668-671
NECROTIZING
FASCIITIS
669
Fig 3. Fibrous tissue of the fascial plane demonstrating acute and chronic inflammation. Adjacent tissue contained fat necrosis. Vascular thrombosis was also present (not shown). (H&E, original magnification x 125.)
DISCUSSION
Fig 1. Preoperative appearance of patient’s perineal lesion. Cutaneous gangrene of the laft labium is evident.
widespread subcutaneous and fascial necrosis. Pathology was diagnostic of necrotizing fasciitis. The child underwent two additional debridements with resection of more necrotic subcutaneous tissue. She received intravenous antibiotics, granulocyte transfusions, and central hyperalimentation. The child received local wound care with saline wet to dry dressing changes resulting in complete healing. She is currently in complete clinical and hematologic remission, on maintenance therapy. 11/zyears after her initial diagnosis of ALL.
Fig 2. Appearance of perineum after debddement. Removal of all affected tissue required colostomy, vesicostomy, and extensive fasciectomies of the left thigh and abdomen.
Necrotizing fasciitis in children is uncommon. In 1973 Wilson and Haltalin reported 11 cases gathered over a 7-year period.5 These children ranged in age from 3 weeks to 17 years. Whereas the extremities are the most commonly involved site in adults, the trunk was most commonly involved in this pediatric series. Most cases in adult patients occur in the presence of a chronic debilitating disease, such as diabetes or vascular insufficiency. The majority of these children had local trauma or a fresh surgical wound as the initiating site. Other reports in the pediatric literature include necrotizing fasciitis arising from omphalitis, after circumcision, or secondary to fetal monitoring scalp electrodes.6-9 The vast majority of these infections in adults are
Fig 4. Uftimate result after four debridements and reconstruction. Solid arrow: split-thickness skin graft donor site. Clear arrow: left labial wound with split-thickness skin graft.
DUNCAN ET AL
670
due to mixed bacterial flora.1-4J0 The synergistic combination of aerobic and anaerobic organisms is considered to be an important aspect leading to the rapid progression of the infection. In contrast, only 1 of 11 cultures was due to mixed flora in Wilson and Haltalin’s series.5 Interestingly, group B Strepococcus appears to be capable of causing necrotizing fasciitis or severe cellulitis in neonates without identifiable predisposing conditions. i1 The two children in the present report had infections apparently due to a single gram-negative organism. In both cases, anaerobic cultures were negative. The occurrence of necrotizing fasciitis in children with ALL has not been reported previously. Fournier’s gangrene, a type of necrotizing fasciitis of the male genitalia, has been reported in patients with malignancies during granulocytopenic episodes from chemotherapy. l2 Children with hematologic malignancies have a multifactorial increased susceptibility to infection.13J4 Cytotoxic agents and steroids used in chemotherapeutic regimens further increase the risk for severe infections. The addition of anthracyclines (daunorubicin and doxyrubicin) to induction chemotherapy increases the risk of mucosal ulcerations with subsequent translocation of bacteria from the gastrointestinal tract to the blood stream. Granulocytopenia, measured objectively as the absolute granulocyte count (AGC), correlates most closely with the increased risk of infection in these children. Necrotizing fasciitis occurred in the present two patients when their AGC was zero. The classic clinical signs of presentation of necrotizing fasciitis include high fever and severe toxicity. The overlying skin frequently shows minimal changes because the early pathological process is confined to the fascia and subcutaneous tissue. Eventually a characteristic pattern of early edema with erythema gives way to bullous changes and eventual cutaneous necrosis. Crepitance of the
soft tissues is a common but not constant finding and plain radiographs of the affected area may show soft tissue gas.15 Skin changes were not reliable in these granulocytopenic patients because their inflammatory responses were blunted and clinical signs of systemic infection were absent early in the disease course. Severe local pain was the only early sign of infection. Treatment in all cases of necrotizing fasciitis is prompt, aggressive surgical excision of involved tissues. Longitudinal incisions are made down to investing fascia, blunt dissection in the fascial plane identifies affected areas, with overlying necrotic tissue separating easily from involved fascia. To limit resection of involved areas greatly increases the risk of further spread and subsequent mortality.1-4 The role of adjunctive therapy becomes especially important in immunosuppressed patients. Synergistic antibiotic combinations are essential in the treatment of any severe infection in granulocytopenic patients and should be continued until the AGC is greater than 500/mm3.16J7 Granulocyte transfusions may have utility while neutropenia exists with evidence of ongoing infection. l8 Both of the present patients received granulocytes in this setting. In addition, the first patient received intravenous gamma globulin. Finally, routine supportive surgical measures must be strictly followed. Saline wet to dry dressing changes were meticulously performed in both children. Wounds were serially assessed for the need for further surgical debridement. Aggressive nutritional support with the use of intravenous hyperalimentation when necessary should be carried out. Both of these children received intravenous hyperalimentation as part of their successful treatment regimens. In summary, a high index of suspicion combined with prompt, multimodality intervention resulted in a successful outcome in these two children.
REFERENCES 1. Ahrenholz DH: Necrotizing soft-tissue infections. Surg Clin North Am 68:199-214,1988 2. Gozal D, Ziser A, Shupak A, et al: Necrotizing fasciitis. Arch Surg 121:233-235,1985 3. Freischlag JA, Ajalat G, Busuttil RW: Treatment of necrotizing infections, the need for a new approach. Am J Surg 149:751755,1985 4. Miller JD: The importance of early diagnosis and surgical treatment of necrotizing fasciitis. Surg Gynecol Obstet 157:197200,1983 5. Wilson HD, Haltalin KC: Acute necrotizing fasciitis in childhood. Am J Dis Child 125:591-595,1973 6. Kosloske AM, CushingAH, Woodside JR, et al: Cellulitis and necrotizing fasciitis of the abdominal wall in pediatric patients. J Pediatr Surg 16:246-251, 1981 7. Goldberg GN, Hansen RC, Lynch PJ: Necrotizing fasciitis in
infancy: Report of three cases and review of the literature. Pediatr Dermatol2:55-63, 1982 8. Woodside JR: Necrotizing fasciitis after neonatal circumcision. Am J Dis Child 134:301-302,198O 9. Siddiqi SF, Taylor PM: Necrotizing fasciitis of the scalp. Am J Dis Child 136:226-228,1982 10. Giuliano A, Lewis F, Hadley K, et al: Bacteriology of necrotizing fasciitis. Am J Surg 134:52-57, 1977 11. Ramamurthy RS, Srinivisan G, Jacobs NM: Necrotizing fasciitis and necrotizing cellulitis due to group B Streptococcus. Am J Dis Child 131:1169-1170,1977 12. Radelli F, Volpe AD, Colombi M. et al: Acute gangrene of the scrotum and penis in four hematologic patients. Cancer 60:1462-1464, 1987 13. Barson WJ, Brady MT: Management of infections in children with cancer. Hematol Oncol Clin North Am 1:801-839,1987
NECROTIZING
FASCIITIS
14. Skelton J, Pizza PA: Problems of intensive therapy in childhood cancer. Cancer 58:488-503,1986 15. Fisher JR, Conway MJ, Takeshita RT, et al: Necrotizing fasciitis: Importance of roentgenographic studies for soft-tissue gas. JAMA 241:803-808, 1979 16. Schimpf SC: Empiric antibiotic therapy for granulocytopenic cancer patients. Am J Med 80:13-20, 1986 (suppl SC)
671
17. Klastersky J: The role of new penicillins and cephalosporins in the management of infection in granulocytopenic patients. Clin Hematol 13:587-598, 1984 18. Buckner CD, Clift RA: Prophylaxis and treatment of the immunocompromised host by granulocyte transfusions. Clin Hemato1 13:557-570. 1984
N. Scott Adzick,
Alfred
A. delorimier,
Michael
Seymour
Zoger,
and Michael
R. Harrison
With
T. Longaker,
Linda D. Ferrell,
San Francisco, California l Necrotizing fasciitis is a severe, soft tissue infection, and is an unusual condition in children. The cornerstone of therapy is prompt, aggressive surgical treatment. Despite vigorous treatment, mortality rates are high. We report the occurrence of necrotizing fasciitis in two children during the granulocytopenic phase of induction chemotherapy for acute lymphoblastic leukemia. The diagnosis and treatment of necrotizing fasciitis in these two children was made more difficult by their underlying disease and its chemotherapy. The successful treatment of their infections relied on a multimodality approach. Aggressive surgical debridement was the mainstay of therapy. Adjuvant therapy was vital to the successful outcomes and included meticulous wound care, intravenous hyperalimentation, appropriate antibiotics, and granulocyte transfusions. Copyright D 1992 by W.B. Saunders Company INDEX WORDS: leukemia.
Necrotizing
fasciitis;
acute lymphoblastic
N
ECROTIZING fasciitis is an uncommon, severe soft tissue infection characterized by necrosis of subcutaneous fat and fascia. The process is usually accompanied by severe systemic toxicity and high mortality rates.1-4 Necrotizing fasciitis is a rare entity in children. In the past year we have encountered two cases of necrotizing fasciitis in children with null cell acute lymphoblastic leukemia (ALL). Both of these children were profoundly neutropenic during the induction phase of chemotherapy. The diagnosis and treatment of this condition were made much more difficult by the underlying disease and chemotherapy. The eventual successful outcome was due to a multimodality approach utilizing aggressive surgical debridement and wound care as the cornerstone of therapy. CASE
REPORTS
Case 1 A 3-year-old white girl presented with recent onset of easy bruising, epistaxis, and hepatosplenomegally. Complete blood count showed 150,000 white blood cells with 95% blast forms. Bone
From the Department of Pediatric Surgery, University of California, San Francisco, San Francisco, CA. Address reprint requests to Michael R. Ham’son, MD, University of California, San Francisco, 3rd and Pamassus Aves, 585HSE, San Francisco, CA 94143. Copyright o 1992 by W.B. Saunders Company 0022-34681921270%0036$03.00/0
668
marrow aspirate and biopsy were consistent with null cell ALL. Induction chemotherapy was begun with vincristine, L-asparaginase, prednisone, daunomycin, and intrathecal methotrexate. On the 16th day of chemotherapy, a rash was noted on the patient’s left labium with extension to the buttocks. The child was lethargic and anorexic and complained of severe vaginal pain. The child was afebrile at that point. Topical Nystatin was administered for a presumed monilial rash. The patient’s absolute granulocyte count at that time was zero. Two days later, the first slight temperature elevation (382°C) developed. Left labial swelling and exquisite tenderness of the area were now noted. Broad-spectrum antibiotics were begun and the child underwent incision and drainage of the left labium. Thin serosanguinous fluid was expressed from the wound. Culture of this material and blood cultures obtained at that time grew Pseudomonas aeruginosa. Anaerobic cultures were negative. Three days later, there was rapid progression of the child’s perineal lesion with obvious cutaneous gangrene of the area (Fig 1). Erythematous. mottled, edematous changes of the skin extending to the abdominal wall and left thigh were now present. Emergency debridement was performed with extensive fasciotomies of the abdominal wall and left thigh (Fig 2). A left labial resection, diverting colostomy and vesicostomy were also performed. Pathological specimens showed widespread necrosis at the fascial level compatible with necrotizing fasciitis (Fig 3). Broad-spectrum antibiotics were continued throughout this period. Granulocyte transfusions, intravenous gamma globulin, and intravenous hyperalimentation were also given. Three subsequent debridements were necessary to completely remove affected tissue. The abdominal and thigh wounds were eventually closed primarily, and a split thickness skin graft was performed to close the labial wound (Fig 4). The child has subsequently had her colostomy and vesicostomy taken down. She recovered fully after a protracted course and remains in hematologic remission 2 years after her initial diagnosis of ALL, off of all medications.
Case 2 An 18-month-old white girl was admitted with a l-month history of an upper respiratory tract infection, lethargy, and easy bruising. Complete blood count had 44,000 white blood cells with 100% lymph forms. Bone marrow aspirate and biopsy demonstrated a null cell ALL. The patient was started on induction chemotherapy with the same regimen as case 1. The patient undetwent a repeat right iliac crest bone marrow biopsy on the 14th day of chemotherapy that demonstrated a hypocellular marrow without evidence of leukemia. The patient’s absolute granulocyte count at the time was zero. Four days later, a small area of cellulitis was noted at the biopsy site. The child was afebrile at that time. Incision and drainage with biopsy of this site were performed. Both blood and tissue cultures subsequently grew a multiply resistant E coli. Anaerobic cultures were negative. The cellulitis at the biopsy site remained unchanged until 4 days later when progressive erythema and edema over an extensive area of the child’s sacral region were noted. Surgical exploration showed
JournalofPediafric Surgery, Vol 27, No 5 (May), 1992: pp 668-671
NECROTIZING
FASCIITIS
669
Fig 3. Fibrous tissue of the fascial plane demonstrating acute and chronic inflammation. Adjacent tissue contained fat necrosis. Vascular thrombosis was also present (not shown). (H&E, original magnification x 125.)
DISCUSSION
Fig 1. Preoperative appearance of patient’s perineal lesion. Cutaneous gangrene of the laft labium is evident.
widespread subcutaneous and fascial necrosis. Pathology was diagnostic of necrotizing fasciitis. The child underwent two additional debridements with resection of more necrotic subcutaneous tissue. She received intravenous antibiotics, granulocyte transfusions, and central hyperalimentation. The child received local wound care with saline wet to dry dressing changes resulting in complete healing. She is currently in complete clinical and hematologic remission, on maintenance therapy. 11/zyears after her initial diagnosis of ALL.
Fig 2. Appearance of perineum after debddement. Removal of all affected tissue required colostomy, vesicostomy, and extensive fasciectomies of the left thigh and abdomen.
Necrotizing fasciitis in children is uncommon. In 1973 Wilson and Haltalin reported 11 cases gathered over a 7-year period.5 These children ranged in age from 3 weeks to 17 years. Whereas the extremities are the most commonly involved site in adults, the trunk was most commonly involved in this pediatric series. Most cases in adult patients occur in the presence of a chronic debilitating disease, such as diabetes or vascular insufficiency. The majority of these children had local trauma or a fresh surgical wound as the initiating site. Other reports in the pediatric literature include necrotizing fasciitis arising from omphalitis, after circumcision, or secondary to fetal monitoring scalp electrodes.6-9 The vast majority of these infections in adults are
Fig 4. Uftimate result after four debridements and reconstruction. Solid arrow: split-thickness skin graft donor site. Clear arrow: left labial wound with split-thickness skin graft.
DUNCAN ET AL
670
due to mixed bacterial flora.1-4J0 The synergistic combination of aerobic and anaerobic organisms is considered to be an important aspect leading to the rapid progression of the infection. In contrast, only 1 of 11 cultures was due to mixed flora in Wilson and Haltalin’s series.5 Interestingly, group B Strepococcus appears to be capable of causing necrotizing fasciitis or severe cellulitis in neonates without identifiable predisposing conditions. i1 The two children in the present report had infections apparently due to a single gram-negative organism. In both cases, anaerobic cultures were negative. The occurrence of necrotizing fasciitis in children with ALL has not been reported previously. Fournier’s gangrene, a type of necrotizing fasciitis of the male genitalia, has been reported in patients with malignancies during granulocytopenic episodes from chemotherapy. l2 Children with hematologic malignancies have a multifactorial increased susceptibility to infection.13J4 Cytotoxic agents and steroids used in chemotherapeutic regimens further increase the risk for severe infections. The addition of anthracyclines (daunorubicin and doxyrubicin) to induction chemotherapy increases the risk of mucosal ulcerations with subsequent translocation of bacteria from the gastrointestinal tract to the blood stream. Granulocytopenia, measured objectively as the absolute granulocyte count (AGC), correlates most closely with the increased risk of infection in these children. Necrotizing fasciitis occurred in the present two patients when their AGC was zero. The classic clinical signs of presentation of necrotizing fasciitis include high fever and severe toxicity. The overlying skin frequently shows minimal changes because the early pathological process is confined to the fascia and subcutaneous tissue. Eventually a characteristic pattern of early edema with erythema gives way to bullous changes and eventual cutaneous necrosis. Crepitance of the
soft tissues is a common but not constant finding and plain radiographs of the affected area may show soft tissue gas.15 Skin changes were not reliable in these granulocytopenic patients because their inflammatory responses were blunted and clinical signs of systemic infection were absent early in the disease course. Severe local pain was the only early sign of infection. Treatment in all cases of necrotizing fasciitis is prompt, aggressive surgical excision of involved tissues. Longitudinal incisions are made down to investing fascia, blunt dissection in the fascial plane identifies affected areas, with overlying necrotic tissue separating easily from involved fascia. To limit resection of involved areas greatly increases the risk of further spread and subsequent mortality.1-4 The role of adjunctive therapy becomes especially important in immunosuppressed patients. Synergistic antibiotic combinations are essential in the treatment of any severe infection in granulocytopenic patients and should be continued until the AGC is greater than 500/mm3.16J7 Granulocyte transfusions may have utility while neutropenia exists with evidence of ongoing infection. l8 Both of the present patients received granulocytes in this setting. In addition, the first patient received intravenous gamma globulin. Finally, routine supportive surgical measures must be strictly followed. Saline wet to dry dressing changes were meticulously performed in both children. Wounds were serially assessed for the need for further surgical debridement. Aggressive nutritional support with the use of intravenous hyperalimentation when necessary should be carried out. Both of these children received intravenous hyperalimentation as part of their successful treatment regimens. In summary, a high index of suspicion combined with prompt, multimodality intervention resulted in a successful outcome in these two children.
REFERENCES 1. Ahrenholz DH: Necrotizing soft-tissue infections. Surg Clin North Am 68:199-214,1988 2. Gozal D, Ziser A, Shupak A, et al: Necrotizing fasciitis. Arch Surg 121:233-235,1985 3. Freischlag JA, Ajalat G, Busuttil RW: Treatment of necrotizing infections, the need for a new approach. Am J Surg 149:751755,1985 4. Miller JD: The importance of early diagnosis and surgical treatment of necrotizing fasciitis. Surg Gynecol Obstet 157:197200,1983 5. Wilson HD, Haltalin KC: Acute necrotizing fasciitis in childhood. Am J Dis Child 125:591-595,1973 6. Kosloske AM, CushingAH, Woodside JR, et al: Cellulitis and necrotizing fasciitis of the abdominal wall in pediatric patients. J Pediatr Surg 16:246-251, 1981 7. Goldberg GN, Hansen RC, Lynch PJ: Necrotizing fasciitis in
infancy: Report of three cases and review of the literature. Pediatr Dermatol2:55-63, 1982 8. Woodside JR: Necrotizing fasciitis after neonatal circumcision. Am J Dis Child 134:301-302,198O 9. Siddiqi SF, Taylor PM: Necrotizing fasciitis of the scalp. Am J Dis Child 136:226-228,1982 10. Giuliano A, Lewis F, Hadley K, et al: Bacteriology of necrotizing fasciitis. Am J Surg 134:52-57, 1977 11. Ramamurthy RS, Srinivisan G, Jacobs NM: Necrotizing fasciitis and necrotizing cellulitis due to group B Streptococcus. Am J Dis Child 131:1169-1170,1977 12. Radelli F, Volpe AD, Colombi M. et al: Acute gangrene of the scrotum and penis in four hematologic patients. Cancer 60:1462-1464, 1987 13. Barson WJ, Brady MT: Management of infections in children with cancer. Hematol Oncol Clin North Am 1:801-839,1987
NECROTIZING
FASCIITIS
14. Skelton J, Pizza PA: Problems of intensive therapy in childhood cancer. Cancer 58:488-503,1986 15. Fisher JR, Conway MJ, Takeshita RT, et al: Necrotizing fasciitis: Importance of roentgenographic studies for soft-tissue gas. JAMA 241:803-808, 1979 16. Schimpf SC: Empiric antibiotic therapy for granulocytopenic cancer patients. Am J Med 80:13-20, 1986 (suppl SC)
671
17. Klastersky J: The role of new penicillins and cephalosporins in the management of infection in granulocytopenic patients. Clin Hematol 13:587-598, 1984 18. Buckner CD, Clift RA: Prophylaxis and treatment of the immunocompromised host by granulocyte transfusions. Clin Hemato1 13:557-570. 1984
